RU2814952C2 - EMBODIMENTS OF IGG-Fc FOR USE IN VETERINARY SCIENCE - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology, specifically to embodiments of IgG-Fc polypeptides of domestic animals. Invention provides obtaining polypeptide IgG-Fc components having low binding affinity with C1q and CD16 and/or low antibody-dependent cell cytotoxicity (ADCC), as well as fused polypeptides based thereon with GLP-1 or glucagon, having increased half-life in blood serum.

EFFECT: invention can be used in veterinary science for treating diabetes, obesity and metabolic disease associated with diabetes or obesity.

61 cl, 7 dwg, 10 tbl, 17 ex

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to US Provisional Application No. 62/545858, filed August 15, 2017, which is incorporated herein by reference in its entirety for all purposes.

FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

[0002] The present invention relates to IgG-Fc variants (IgG-Fc polypeptide variants) in companion animals having improved functions including increased protein A binding (eg, for ease of purification), reduced C1q binding (eg, to reduce complement-mediated immune response), reduced CD16 binding (eg, to reduce the induction of antibody-dependent cellular cytotoxicity (ADCC)), increased stability and/or the ability to form heterodimeric proteins. Variants of the IgG-Fc polypeptides of the present invention may have widespread use in companion animal therapeutics. For example, variants of IgG-Fc polypeptides can be used in the design and manufacture of long-acting GLP1 polypeptides for the treatment of, for example, diabetes mellitus, obesity or related diseases in companion animals such as canines, felines and equines. In addition, variants of IgG-Fc polypeptides can be used in the design and manufacture of antibodies or fusion proteins for the treatment of various diseases in companion animals.

BACKGROUND OF THE ART

[0003] IgG-Fc plays an important role in Fc region-mediated immunoglobulin functions through interaction with FcRn, Fc receptor and C1q. In companion animals, different IgG subtypes differ in these functions, which must be considered when selecting a particular IgG antibody or IgG Fc region fusion protein for therapeutic or diagnostic use. For example, weak or undetectable binding affinity for C1q or CD16 in an IgG subtype may be advantageous. In addition, the ability of IgG-Fc to bind Protein A may be useful for purification using a Protein A affinity purification method.

[0004] However, most IgG-Fc subtypes in the canine, feline, and equine families lack the ability to bind Protein A, have weak or undetectable binding affinity for CD16, and weak or undetectable binding affinity for C1q. For example, of the four IgG-Fc subtypes in canines (IgG-A, IgG-B, IgG-C and IgG-D), the Fc region of only IgG-B has a noticeable binding affinity for protein A. At the same time While the Fc regions of only IgG-A and IgG-D in representatives of the canine family do not have or have weak binding to C1q or CD16. Antibodies and Fc fusion proteins containing variants of IgG-Fc polypeptides that have reduced binding to C1q and/or CD16 and/or that are capable of binding to protein A are desirable.

[0005] Glucagon-like peptide-1 (GLP1) is a potent anti-hyperglycemic hormone that plays an important role in regulating blood glucose levels. Natural GLP1 has an in vivo half-life of approximately 2 minutes. Long-acting GLP1 polypeptides can be used to treat diabetes and obesity, prevent diabetes, control hyperglycemia, lower lipids, treat diseases caused by increased blood glucose levels, suppress gastrointestinal motility, slow gastric emptying and/or reduce food consumption. There remains a need today for long-acting GLP1 polypeptides for the control of high blood glucose levels or diseases induced by uncontrolled blood glucose levels in companion animals such as canines, felines and equines.

SUMMARY OF THE INVENTION

Embodiment 1. A polypeptide comprising a variant IgG-Fc polypeptide containing at least one amino acid modification relative to a wild-type IgG-Fc polypeptide in one companion animal species, wherein the variant IgG-Fc polypeptide has increased protein A binding affinity relative to the polypeptide Wild type IgG-Fc.

Embodiment 2. A polypeptide comprising a variant IgG-Fc polypeptide containing at least one amino acid modification relative to a wild-type IgG-Fc polypeptide of one companion animal species, wherein the variant IgG-Fc polypeptide has reduced binding affinity to C1q and/or CD16 relative to the wild type IgG-Fc polypeptide.

Embodiment 3. The polypeptide of Embodiment 1 or Embodiment 2, wherein the IgG-Fc polypeptide variant binds to C1q and/or CD16 with a dissociation constant (Kd) greater than 5×10 ^-6 M, greater than 1×10 ^-5 M, above 5×10 ^-5 M, above 1×10 ^-4 M, above 5×10 ^-4 M or above 1×10 ^-3 M, measured by biolayer interferometry.

Embodiment 4. The polypeptide of any one of the preceding embodiments, wherein the variant IgG-Fc polypeptide has increased protein A binding affinity relative to the wild-type IgG-Fc polypeptide.

Embodiment 5. The polypeptide according to any of the preceding embodiments, wherein the IgG-Fc polypeptide variant binds to protein A with a dissociation constant (Kd) below 5×10 ^-6 M, below 1×10 ^-6 M, below 5×10 ^{- 7} M, below 1×10 ^-7 M, below 5×10 ^-8 M, below 1×10 ^-8 M, below 5×10 -9 M, below 1× ^{10 -9 M} , below 5×10 ^-10 M , below 1×10 ^-10 M, below 5×10 ^-11 M, below 1×10 ^-11 M, below 5×10 ^-12 M or below 1×10 ^-12 M, measured by biolayer interferometry.

Embodiment 6. The polypeptide according to any of the preceding embodiments, wherein the companion animal is a feline, canine, or equine.

Embodiment 7. The polypeptide of any one of the preceding embodiments, wherein the wild type IgG-Fc polypeptide is:

a) canine IgG-A-Fc, IgG-B-Fc, IgG-C-Fc or IgG-D-Fc;

b) equine IgG1-Fc, IgG2-Fc, IgG3-Fc, IgG4-Fc, IgG5-Fc, IgG6-Fc or IgG7-Fc; or

c) Feline IgG1a-Fc, IgG1b-Fc or IgG2-Fc.

Embodiment 8. A polypeptide comprising a variant IgG-Fc polypeptide comprising at least one amino acid modification in the hinge region relative to a wild-type or equine feline IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide has increased production in a recombinant system, and/ or increased formation of disulfide bonds at the hinge region relative to the wild-type IgG-Fc polypeptide, as determined by SDS-PAGE under reducing and/or non-reducing conditions.

Embodiment 9. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) at least one amino acid substitution relative to a wild-type feline IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81 , SEQ ID NO: 117 or SEQ ID NO: 118;

b) at least one amino acid substitution relative to a wild-type equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 3 in SEQ ID NO: 129; and/or

c) at least one amino acid substitution relative to a wild-type equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 20 in SEQ ID NO: 129.

Embodiment 10. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) at least one amino acid substitution relative to a wild-type feline IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains an amino acid substitution at position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117 or SEQ ID NO: 118;

b) at least one amino acid substitution relative to a wild-type equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains an amino acid substitution at position 3 in SEQ ID NO: 129; and/or

c) at least one amino acid substitution relative to a wild-type equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains an amino acid substitution at position 20 in SEQ ID NO: 129.

Embodiment 11. The polypeptide according to any of the preceding embodiments, wherein the variant IgG-Fc polypeptide comprises:

a) at least one amino acid substitution relative to a wild-type feline IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains a proline at a position corresponding to position 16, or at position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117 or SEQ ID NO: 118;

b) at least one amino acid substitution relative to a wild-type equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 3, or at position 3 in SEQ ID NO: 129; and/or

c) at least one amino acid substitution relative to a wild-type equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide contains a proline at a position corresponding to position 20, or at position 20 in SEQ ID NO: 129.

Embodiment 12. The polypeptide of any one of the preceding embodiments, wherein the variant IgG-Fc polypeptide comprises a hinge region or hinge region portion from a different isotype IgG-Fc polypeptide.

Embodiment 13. The polypeptide of any one of the preceding embodiments, wherein the variant IgG-Fc polypeptide comprises a hinge region or hinge region portion from a wild-type feline IgG-1a-Fc polypeptide, from a wild-type feline IgG-1b-Fc polypeptide, or from wild-type equine IgG1-Fc polypeptide.

Embodiment 14. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises SEQ ID NO: 19, SEQ ID NO: 125, or SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135.

Embodiment 15. A polypeptide comprising the amino acid sequence of SEQ ID NO: 19, SEQ ID NO: 125 or SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135.

Embodiment 16. A polypeptide comprising a variant IgG2-Fc polypeptide comprising at least one amino acid substitution relative to a wild-type feline IgG2-Fc polypeptide, wherein at least one amino acid substitution is cysteine, and wherein the variant IgG2-Fc polypeptide is capable of the formation of at least one additional interchain disulfide bond relative to the wild-type feline IgG2-Fc polypeptide.

Embodiment 17. The polypeptide of any one of the preceding embodiments, wherein the variant IgG-Fc polypeptide contains at least one amino acid substitution relative to the wild-type feline IgG-Fc polypeptide, wherein the at least one amino acid substitution is cysteine, and wherein the variant polypeptide The IgG-Fc is capable of forming at least one additional interchain disulfide bond relative to the wild-type feline IgG2-Fc polypeptide.

Embodiment 18. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant contains a cysteine at a position corresponding to position 8, position 9, position 10, position 11, position 12, position 13, position 14, position 15, or position 16 in the sequence SEQ ID NO: 16.

Embodiment 19. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant contains a cysteine at a position corresponding to position 14 in SEQ ID NO: 16.

Embodiment 20. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant contains a cysteine at position 14 in SEQ ID NO: 16.

Embodiment 21. A polypeptide according to any of the preceding embodiments, wherein the IgG-Fc polypeptide variant is at least 90% identical, at least 95% identical, at least 97% identical, or at least 99% identical amino acid sequence SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 100, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156 or SEQ ID NO: 157.

Embodiment 22. The polypeptide according to any of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises SEQ ID NO: 17.

Embodiment 23. A polypeptide comprising the amino acid sequence of SEQ ID NO: 17.

Embodiment 24. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at a position corresponding to position 21 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 23 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 25 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 80 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 205 in SEQ ID NO: 1, and/or an amino acid substitution at a position corresponding to position 207 in SEQ ID NO: 1;

b) an amino acid substitution at a position corresponding to position 21 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 23 in SEQ ID NO: 3, and/or an amino acid substitution at a position corresponding to position 24 in SEQ ID NO: 3;

c) an amino acid substitution at a position corresponding to position 21 in SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 23 in SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 25 in SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 80 in SEQ ID NO: 4, and/or an amino acid substitution at a position corresponding to position 207 in SEQ ID NO: 4;

d) an amino acid substitution at a position corresponding to position 15 in SEQ ID NO: 64 and/or an amino acid substitution at a position corresponding to position 203 in SEQ ID NO: 64;

e) an amino acid substitution at a position corresponding to position 199 in SEQ ID NO: 67 and/or an amino acid substitution at a position corresponding to position 200 in SEQ ID NO: 67; and/or

f) an amino acid substitution at a position corresponding to position 199 in SEQ ID NO: 68, an amino acid substitution at a position corresponding to position 200 in SEQ ID NO: 68, an amino acid substitution at a position corresponding to position 201 in SEQ ID NO: 68, and/or an amino acid substitution at a position corresponding to position 202 in SEQ ID NO: 68.

Embodiment 25. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at position 21 in SEQ ID NO: 1, an amino acid substitution at position 23 in SEQ ID NO: 1, an amino acid substitution at position 25 in SEQ ID NO: 1, an amino acid substitution at position 80 in SEQ ID NO: 1, an amino acid substitution at position 205 in SEQ ID NO: 1 and/or an amino acid substitution at position 207 in SEQ ID NO: 1;

b) an amino acid substitution at position 21 in SEQ ID NO: 3, an amino acid substitution at position 23 in SEQ ID NO: 3, and/or an amino acid substitution at position 24 in SEQ ID NO: 3;

c) an amino acid substitution at position 21 in SEQ ID NO: 4, an amino acid substitution at position 23 in SEQ ID NO: 4, an amino acid substitution at position 25 in SEQ ID NO: 4, an amino acid substitution at position 80 in SEQ ID NO: 4, and /or amino acid substitution at position 207 in SEQ ID NO: 4;

d) an amino acid substitution at position 15 in SEQ ID NO: 64 and/or an amino acid substitution at position 203 in SEQ ID NO: 64;

e) an amino acid substitution at position 199 in SEQ ID NO: 67 and/or an amino acid substitution at position 200 in SEQ ID NO: 67; and/or

f) an amino acid substitution at position 199 in SEQ ID NO: 68, an amino acid substitution at position 200 in SEQ ID NO: 68, an amino acid substitution at position 201 in SEQ ID NO: 68, and/or an amino acid substitution at position 202 in SEQ ID NO: 68.

Embodiment 26. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) threonine at a position corresponding to position 21 in SEQ ID NO: 1, leucine at a position corresponding to position 23 in SEQ ID NO: 1, alanine at a position corresponding to position 25 in SEQ ID NO: 1, glycine at a position corresponding to 80 in SEQ ID NO: 1, an alanine at a position corresponding to position 205 in SEQ ID NO: 1, and/or a histidine at a position corresponding to position 207 in SEQ ID NO: 1;

b) threonine at a position corresponding to position 21 in SEQ ID NO: 3, leucine at a position corresponding to position 23 in SEQ ID NO: 3 and/or isoleucine at a position corresponding to position 24 in SEQ ID NO: 3;

c) threonine at a position corresponding to position 21 in SEQ ID NO: 4, leucine at a position corresponding to position 23 in SEQ ID NO: 4, alanine at a position corresponding to position 25 in SEQ ID NO: 4, glycine at a position corresponding to 80 in SEQ ID NO: 4, and/or a histidine at a position corresponding to position 207 in SEQ ID NO: 4;

d) threonine or valine at a position corresponding to position 15 in SEQ ID NO: 64 and/or tyrosine or valine at a position corresponding to position 203 in SEQ ID NO: 64;

f) leucine at a position corresponding to position 199 in SEQ ID NO: 67 and/or histidine at a position corresponding to position 200 in SEQ ID NO: 67; and/or

f) leucine at position corresponding to position 199 in SEQ ID NO: 68, histidine at position corresponding to position 200 in SEQ ID NO: 68, asparagine at position corresponding to position 201 in SEQ ID NO: 68, and/or histidine at position , corresponding to position 202 in SEQ ID NO: 68.

Embodiment 27. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) threonine at position 21 in SEQ ID NO: 1, leucine at position 23 in SEQ ID NO: 1, alanine at position 25 in SEQ ID NO: 1, glycine at position 80 in SEQ ID NO: 1, alanine at position 205 in SEQ ID NO: 1 and/or histidine at position 207 in SEQ ID NO: 1;

b) threonine at position 21 in SEQ ID NO: 3, leucine at position 23 in SEQ ID NO: 3 and/or isoleucine at position 24 in SEQ ID NO: 3;

c) threonine at position 21 in SEQ ID NO: 4, leucine at position 23 in SEQ ID NO: 4, alanine at position 25 in SEQ ID NO: 4, glycine at position 80 in SEQ ID NO: 4 and/or histidine at position 207 in SEQ ID NO: 4;

d) threonine or valine at position 15 in SEQ ID NO: 64 and/or tyrosine or valine at position 203 in SEQ ID NO: 64;

e) leucine at position 199 in SEQ ID NO: 67 and/or histidine at position 200 in SEQ ID NO: 67; and/or

f) leucine at position 199 in SEQ ID NO: 68, histidine at position 200 in SEQ ID NO: 68, asparagine at position 201 in SEQ ID NO: 68, and/or histidine at position 202 in SEQ ID NO: 68.

Embodiment 28. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises the amino acid sequence:

a) SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62 or SEQ ID NO: 84; or

b) SEQ ID NO: 19, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75 or SEQ ID NO: 76.

Embodiment 29. A polypeptide comprising the amino acid sequence SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 84, SEQ ID NO: 19, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75 or SEQ ID NO: 76.

Embodiment 30. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at a position corresponding to position 93 in SEQ ID NO: 2, or an amino acid substitution at a position corresponding to position 93 in SEQ ID NO: 3;

b) an amino acid substitution at a position corresponding to position 87 in SEQ ID NO: 63, an amino acid substitution at a position corresponding to position 87 in SEQ ID NO: 65, an amino acid substitution at a position corresponding to position 87 in SEQ ID NO: 66, or an amino acid substitution in a position corresponding to position 87 in SEQ ID NO: 69; or

c) an amino acid substitution at a position corresponding to position 198 in SEQ ID NO: 80, or an amino acid substitution at a position corresponding to position 198 in SEQ ID NO: 81.

Embodiment 31. The polypeptide according to any of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at position 93 in SEQ ID NO: 2, or an amino acid substitution at position 93 in SEQ ID NO: 3;

b) an amino acid substitution at position 87 in SEQ ID NO: 63, an amino acid substitution at position 87 in SEQ ID NO: 65, an amino acid substitution at position 87 in SEQ ID NO: 66, or an amino acid substitution at position 87 in SEQ ID NO: 69 ; or

c) an amino acid substitution at position 198 in SEQ ID NO: 80, or an amino acid substitution at position 198 in SEQ ID NO: 81.

Embodiment 32. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) arginine at a position corresponding to position 93 in SEQ ID NO: 2, or arginine at a position corresponding to position 93 in SEQ ID NO: 3;

b) a serine at a position corresponding to position 87 in SEQ ID NO: 63, a substitution for a serine at a position corresponding to position 87 in SEQ ID NO: 65, a serine at a position corresponding to position 87 in SEQ ID NO: 66, or a serine at a position corresponding to position 87 in SEQ ID NO: 69; or

c) an alanine at a position corresponding to position 198 in SEQ ID NO: 80, or an alanine at a position corresponding to position 198 in SEQ ID NO: 81.

Embodiment 33. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) arginine at position 93 in SEQ ID NO: 2, or arginine at position 93 in SEQ ID NO: 3;

b) serine at position 87 in SEQ ID NO: 63, serine at position 87 in SEQ ID NO: 65, serine at position 87 in SEQ ID NO: 66, or serine at position 87 in SEQ ID NO: 69; or

c) alanine at position 198 in SEQ ID NO: 80 or alanine at position 198 in SEQ ID NO: 81.

Embodiment 34. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises the amino acid sequence:

a) SEQ ID NO: 78, SEQ ID NO: 79 or SEQ ID NO: 84; or

b) SEQ ID NO: 70, SEQ ID NO: 73, SEQ ID NO: 74 or SEQ ID NO: 77; or

c) SEQ ID NO: 82 or SEQ ID NO: 83.

Embodiment 35. A polypeptide comprising the amino acid sequence of SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 84, SEQ ID NO: 70, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 77, SEQ ID NO: 82 or SEQ ID NO: 83.

Embodiment 36. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at a position corresponding to position 5 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 38 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 39 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 97 in SEQ ID NO: 2, and/or an amino acid substitution at a position corresponding to position 98 in SEQ ID NO: 2; or

b) an amino acid substitution at a position corresponding to position 5 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 38 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 39 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 97 in SEQ ID NO: 3, and/or an amino acid substitution at a position corresponding to position 98 in SEQ ID NO: 3.

Embodiment 37. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at position 5 in SEQ ID NO: 2, an amino acid substitution at position 38 in SEQ ID NO: 2, an amino acid substitution at position 39 in SEQ ID NO: 2, an amino acid substitution at position 97 in SEQ ID NO: 2, and /or amino acid substitution at position 98 in SEQ ID NO: 2; or

b) an amino acid substitution at position 5 in SEQ ID NO: 3, an amino acid substitution at position 38 in SEQ ID NO: 3, an amino acid substitution at position 39 in SEQ ID NO: 3, an amino acid substitution at position 97 in SEQ ID NO: 3, and /or an amino acid substitution at position 98 in SEQ ID NO: 3.

Embodiment 38. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) proline at a position corresponding to position 5 in SEQ ID NO: 2, glycine at a position corresponding to position 38 in SEQ ID NO: 2, arginine at a position corresponding to position 39 in SEQ ID NO: 2, isoleucine at a position corresponding to 97 in SEQ ID NO: 2, and/or glycine at a position corresponding to position 98 in SEQ ID NO: 2; or

b) proline at a position corresponding to position 5 in SEQ ID NO: 3, glycine at a position corresponding to position 38 in SEQ ID NO: 3, arginine at a position corresponding to position 39 in SEQ ID NO: 3, isoleucine at a position corresponding to 97 in SEQ ID NO: 3, and/or glycine at a position corresponding to position 98 in SEQ ID NO: 3.

Embodiment 39. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) proline at position 5 in SEQ ID NO: 2, glycine at position 38 in SEQ ID NO: 2, arginine at position 39 in SEQ ID NO: 2, isoleucine at position 97 in SEQ ID NO: 2 and/or glycine at position 98 of SEQ ID NO: 2; or

b) proline at position 5 in SEQ ID NO: 3, glycine at position 38 in SEQ ID NO: 3, arginine at position 39 in SEQ ID NO: 3, isoleucine at position 97 in SEQ ID NO: 3 and/or glycine at position 98 in SEQ ID NO: 3.

Embodiment 40. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises the amino acid sequence:

a) SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146 or SEQ ID NO: 147; or

b) SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156 or SEQ ID NO: 157.

Embodiment 41. A polypeptide comprising the amino acid sequence of SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO : 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 154 , SEQ ID NO: 155, SEQ ID NO: 156 or SEQ ID NO: 157.

Embodiment 42. A polypeptide comprising a variant IgG-Fc polypeptide comprising:

a) tyrosine or tryptophan at a position corresponding to position 138 in SEQ ID NO: 1, tyrosine or tryptophan at a position corresponding to position 137 in SEQ ID NO: 2, tyrosine or tryptophan at a position corresponding to position 137 in SEQ ID NO: 3, or tyrosine or tryptophan at a position corresponding to position 138 in SEQ ID NO: 4; or

b) tyrosine or tryptophan at a position corresponding to position 154 in SEQ ID NO: 16, tyrosine or tryptophan at a position corresponding to position 154 in SEQ ID NO: 80 or SEQ ID NO: 117, or tyrosine or tryptophan at a position corresponding to position 154 in SEQ ID NO: 81 or SEQ ID NO: 118.

Embodiment 43. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) tyrosine or tryptophan at position 138 in SEQ ID NO: 1, tyrosine or tryptophan at position 137 in SEQ ID NO: 2, tyrosine or tryptophan at position 137 in SEQ ID NO: 3, or tyrosine or tryptophan at position 138 in SEQ ID NO: 4; or

b) tyrosine or tryptophan at position 154 in SEQ ID NO: 16, tyrosine or tryptophan at position 154 in SEQ ID NO: 80 or SEQ ID NO: 117, or tyrosine or tryptophan at a position corresponding to position 154 in SEQ ID NO: 81 or SEQ ID NO: 118.

Embodiment 44. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 115, SEQ ID NO: 119, SEQ ID NO: 121 or SEQ ID NO: 123.

Embodiment 45. A polypeptide comprising the amino acid sequence SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 115, SEQ ID NO: 119, SEQ ID NO: 121 or SEQ ID NO: 123.

Embodiment 46. A continuous polypeptide comprising a polypeptide according to any of the preceding embodiments and a glucagon-like peptide-1 (GLP-1) polypeptide.

Embodiment 47. A continuous polypeptide comprising a polypeptide according to any of the preceding embodiments and a glucagon polypeptide.

Embodiment 48. A polypeptide comprising a variant IgG-Fc polypeptide comprising:

a) serine at a position corresponding to position 138 in SEQ ID NO: 1, serine at a position corresponding to position 137 in SEQ ID NO: 2, serine at a position corresponding to position 137 in SEQ ID NO: 3, serine at a position corresponding to 138 in SEQ ID NO: 4, serine at a position corresponding to position 154 in SEQ ID NO: 16, serine at a position corresponding to position 154 in SEQ ID NO: 80 or SEQ ID NO: 117, or serine at a position corresponding to position 154 in SEQ ID NO: 81 or SEQ ID NO: 118;

b) an alanine at a position corresponding to position 140 in SEQ ID NO: 1, an alanine at a position corresponding to position 139 in SEQ ID NO: 2, an alanine at a position corresponding to position 139 in SEQ ID NO: 3, an alanine at a position corresponding to position 140 in SEQ ID NO: 4, an alanine at a position corresponding to position 156 in SEQ ID NO: 16, an alanine at a position corresponding to position 156 in SEQ ID NO: 80 or SEQ ID NO: 117, or an alanine at a position corresponding to position 156 in SEQ ID NO: 81 or SEQ ID NO: 118; and/or

c) threonine at a position corresponding to position 181 in SEQ ID NO: 1, threonine at a position corresponding to position 180 in SEQ ID NO: 2, threonine at a position corresponding to position 180 in SEQ ID NO: 3, threonine at a position corresponding to 181 in SEQ ID NO: 4, threonine at a position corresponding to position 197 in SEQ ID NO: 16, threonine at a position corresponding to position 197 in SEQ ID NO: 80 or SEQ ID NO: 117, or threonine at a position corresponding to position 197 in SEQ ID NO: 81 or SEQ ID NO: 118.

Embodiment 49. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises:

a) serine at position 138 in SEQ ID NO: 1, serine at position 137 in SEQ ID NO: 2, serine at position 137 in SEQ ID NO: 3, serine at position 138 in SEQ ID NO: 4, serine at position 154 in SEQ ID NO: 16, the serine at position 154 in SEQ ID NO: 80 or SEQ ID NO: 117, or the serine at position 154 in SEQ ID NO: 81 or SEQ ID NO: 118;

b) alanine at position 140 in SEQ ID NO: 1, alanine at position 139 in SEQ ID NO: 2, alanine at position 139 in SEQ ID NO: 3, alanine at position 140 in SEQ ID NO: 4, alanine at position 156 in SEQ ID NO: 16, the alanine at position 156 in SEQ ID NO: 80 or SEQ ID NO: 117, or the alanine at position 156 in SEQ ID NO: 81 or SEQ ID NO: 118; and/or;

c) threonine at position 181 in SEQ ID NO: 1, threonine at position 181 in SEQ ID NO: 2, threonine at position 181 in SEQ ID NO: 3, threonine at position 181 in SEQ ID NO: 4, threonine at position 197 in SEQ ID NO: 16, the threonine at position 197 in SEQ ID NO: 80 or SEQ ID NO: 117, or the threonine at position 197 in SEQ ID NO: 81 or SEQ ID NO: 118.

Embodiment 50. The polypeptide of any one of the preceding embodiments, wherein the IgG-Fc polypeptide variant comprises the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO: 122 or SEQ ID NO: 124.

Embodiment 51. A polypeptide comprising the amino acid sequence SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO: 122 or SEQ ID NO: 124.

Embodiment 52. A polypeptide according to any of the preceding embodiments, wherein said polypeptide is glycosylated.

Embodiment 53. The polypeptide of any one of Embodiments 1 to 51, wherein the polypeptide is aglycosylated.

Embodiment 54. A continuous polypeptide comprising the polypeptide of any one of embodiments 48-53 and a glucagon-like peptide-1 (GLP1) polypeptide.

Embodiment 55. A continuous polypeptide comprising the polypeptide of any one of embodiments 48-53 and a glucagon polypeptide.

Embodiment 56. A heterodimeric protein comprising a continuous polypeptide of Embodiment 46 and a continuous polypeptide of Embodiment 54.

Embodiment 57. A heterodimeric protein comprising a continuous polypeptide of Embodiment 47 and a continuous polypeptide of Embodiment 55.

Embodiment 58. The continuous polypeptide or heterodimeric protein of any one of Embodiments 46, 47, or 54-57, wherein the GLP1 polypeptide is a wild-type GLP1 Polypeptide, optionally comprising the amino acid sequence of SEQ ID NO: 85.

Embodiment 59. The continuous polypeptide or heterodimeric protein of any one of Embodiments 46, 47, or 54-58, wherein the GLP1 polypeptide is a variant of the GLP1 polypeptide.

Embodiment 60. The continuous polypeptide or heterodimeric protein of any one of Embodiments 46, 47, or 54-59, wherein the GLP1 polypeptide comprises the amino acid sequence of SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 98, or SEQ ID NO : 99.

Embodiment 61. The continuous polypeptide or heterodimeric protein of any one of Embodiments 46, 47, or 54-60, wherein the glucagon polypeptide is a wild-type glucagon polypeptide, optionally comprising the amino acid sequence of SEQ ID NO: 21.

Embodiment 62. The continuous polypeptide or heterodimeric protein of any one of Embodiments 46, 47, or 54-61, wherein the glucagon polypeptide is a variant of the glucagon polypeptide.

Embodiment 63. A heterodimeric protein containing:

i) a first variant of a canine IgG-Fc polypeptide containing at least one amino acid modification relative to a first wild-type canine IgG-Fc polypeptide, and a second variant of a canine IgG-Fc polypeptide containing at least one amino acid modification relative to a second canine IgG-Fc polypeptide wild type; or

ii) a first variant feline IgG-Fc polypeptide containing at least one amino acid modification relative to the first wild-type feline IgG-Fc polypeptide, and a second variant feline IgG-Fc polypeptide containing at least one amino acid modification relative to the second feline IgG-Fc polypeptide wild type, where:

a) the first variant of the canine IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 138 in SEQ ID NO: 1, position 137 in SEQ ID NO: 2, position 137 in SEQ ID NO: 3, or position 138 in SEQ ID NO: 4;

b) the second variant of the canine IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 138, position 140 and/or position 181 in SEQ ID NO: 1, position 137, position 139 and/or position 180 in SEQ ID NO: 2, position 137, position 139 and/or position 180 in SEQ ID NO: 3, or position 138, position 140 and/or position 181 in SEQ ID NO: 4;

c) the first variant feline IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 154 in SEQ ID NO: 6, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118; and/or

d) the second variant feline IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 154, position 156 and/or position 197 in SEQ ID NO: 6, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117 or SEQ ID NO: 118.

Embodiment 64. The heterodimeric protein of Embodiment 63, wherein the first wild-type canine IgG-Fc polypeptide and the second wild-type canine IgG-Fc polypeptide are of the same IgG subtype, and/or the first wild-type feline IgG-Fc polypeptide and the second feline IgG-Fc polypeptide are of the same IgG subtype. wild-type IgG-Fc polypeptides belong to one IgG subtype.

Embodiment 65. The heterodimeric protein of Embodiment 63, wherein the first wild-type canine IgG-Fc polypeptide and the second wild-type canine IgG-Fc polypeptide are different IgG subtypes, and/or the first wild-type feline IgG-Fc polypeptide and the second feline IgG-Fc polypeptide are of different IgG subtypes. wild-type IgG-Fc polypeptides belong to one IgG subtype.

Embodiment 66. The heterodimeric protein according to any one of embodiments 63-65, wherein:

a) the first variant canine IgG-Fc polypeptide contains tyrosine or tryptophan at a position corresponding to position 138 in SEQ ID NO: 1, position 137 in SEQ ID NO: 2, position 137 in SEQ ID NO: 3 or position 138 in SEQ ID NO: : 4; and/or

b) the first variant feline IgG-Fc polypeptide contains tryptophan at a position corresponding to position 154 in SEQ ID NO: 6, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117 or SEQ ID NO: 118.

Embodiment 67. The heterodimeric protein according to any one of embodiments 63-66, wherein:

a) the second variant canine IgG-Fc polypeptide contains a serine at a position corresponding to position 138, an alanine at a position corresponding to position 140, and/or a threonine at a position corresponding to position 181 in SEQ ID NO: 1, and a serine at a position corresponding to 137, alanine at a position corresponding to position 139 and/or threonine at a position corresponding to position 180 in SEQ ID NO: 2, serine at a position corresponding to position 137, alanine at a position corresponding to position 139 and/or threonine at a position corresponding to 180 in SEQ ID NO: 3, and/or serine at a position corresponding to position 138, alanine at a position corresponding to position 140, and/or threonine at a position corresponding to position 181 in SEQ ID NO: 4; and/or

b) the second variant feline IgG-Fc polypeptide contains a serine at a position corresponding to position 154, an alanine at a position corresponding to position 156 and/or a threonine at a position corresponding to position 197 in SEQ ID NO: 6, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117 or SEQ ID NO: 118.

Embodiment 68. The heterodimeric protein of any one of embodiments 63-67, wherein:

a) the first variant of the canine IgG-Fc polypeptide contains the amino acid sequence SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113 or SEQ ID NO: 115; and/or

b) the first variant feline IgG-Fc polypeptide contains the amino acid sequence of SEQ ID NO: 119, SEQ ID NO: 121 or SEQ ID NO: 123.

Embodiment 69. The heterodimeric protein according to any one of embodiments 63-68, wherein:

a) the second variant of the canine IgG-Fc polypeptide contains the amino acid sequence SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114 or SEQ ID NO: 116; and/or

b) the second variant feline IgG-Fc polypeptide contains the amino acid sequence of SEQ ID NO: 120, SEQ ID NO: 122 or SEQ ID NO: 123.

Embodiment 70. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-69, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises at least one additional amino acid modification relative to the wild-type IgG-Fc polypeptide and have increased binding affinity to protein A relative to the wild-type IgG-Fc polypeptide.

Embodiment 71. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of embodiments 42 to 70, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at a position corresponding to position 21 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 23 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 25 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 80 in SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 205 in SEQ ID NO: 1, and/or an amino acid substitution at a position corresponding to position 207 in SEQ ID NO: 1;

b) an amino acid substitution at a position corresponding to position 21 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 23 in SEQ ID NO: 3, and/or an amino acid substitution at a position corresponding to position 24 in SEQ ID NO: 3; or

c) an amino acid substitution at a position corresponding to position 21 in SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 23 in SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 25 in SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 80 in SEQ ID NO: 4, and/or an amino acid substitution at a position corresponding to position 207 in SEQ ID NO: 4.

Embodiment 72. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-71, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at position 21 in SEQ ID NO: 1, an amino acid substitution at position 23 in SEQ ID NO: 1, an amino acid substitution at position 25 in SEQ ID NO: 1, an amino acid substitution at position 80 in SEQ ID NO: 1, an amino acid substitution at position 205 in SEQ ID NO: 1 and/or an amino acid substitution at position 207 in SEQ ID NO: 1;

b) an amino acid substitution at position 21 in SEQ ID NO: 3, an amino acid substitution at position 23 in SEQ ID NO: 3, and/or an amino acid substitution at position 24 in SEQ ID NO: 3; or

c) an amino acid substitution at position 21 in SEQ ID NO: 4, an amino acid substitution at position 23 in SEQ ID NO: 4, an amino acid substitution at position 25 in SEQ ID NO: 4, an amino acid substitution at position 80 in SEQ ID NO: 4, and /or an amino acid substitution at position 207 in SEQ ID NO: 4.

Embodiment 73. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-72, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) threonine at a position corresponding to position 21 in SEQ ID NO: 1, leucine at a position corresponding to position 23 in SEQ ID NO: 1, alanine at a position corresponding to position 25 in SEQ ID NO: 1, glycine at a position corresponding to 80 in SEQ ID NO: 1, an alanine at a position corresponding to position 205 in SEQ ID NO: 1, and/or a histidine at a position corresponding to position 207 in SEQ ID NO: 1;

b) threonine at a position corresponding to position 21 in SEQ ID NO: 3, leucine at a position corresponding to position 23 in SEQ ID NO: 3, and/or isoleucine at a position corresponding to position 24 in SEQ ID NO: 3; or

c) threonine at a position corresponding to position 21 in SEQ ID NO: 4, leucine at a position corresponding to position 23 in SEQ ID NO: 4, alanine at a position corresponding to position 25 in SEQ ID NO: 4, glycine at a position corresponding to 80 in SEQ ID NO: 4, and/or a histidine at a position corresponding to position 207 in SEQ ID NO: 4.

Embodiment 74. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-73, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) threonine at position 21 in SEQ ID NO: 1, leucine at position 23 in SEQ ID NO: 1, alanine at position 25 in SEQ ID NO: 1, glycine at position 80 in SEQ ID NO: 1, alanine at position 205 in SEQ ID NO: 1 and/or histidine at position 207 in SEQ ID NO: 1;

b) threonine at position 21 in SEQ ID NO: 3, leucine at position 23 in SEQ ID NO: 3 and/or isoleucine at position 24 in SEQ ID NO: 3; or

c) threonine at position 21 in SEQ ID NO: 4, leucine at position 23 in SEQ ID NO: 4, alanine at position 25 in SEQ ID NO: 4, glycine at position 80 in SEQ ID NO: 4 and/or histidine at position 207 in SEQ ID NO: 4.

Embodiment 75. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-74, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises at least one additional amino acid modification relative to the wild-type IgG-Fc polypeptide and have reduced binding affinity to CD16 relative to the wild-type IgG-Fc polypeptide.

Embodiment 76. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-75, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at a position corresponding to position 5 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 38 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 39 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 97 in SEQ ID NO: 2, and/or an amino acid substitution at a position corresponding to position 98 in SEQ ID NO: 2; or

b) an amino acid substitution at a position corresponding to position 5 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 38 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 39 in SEQ ID NO: 3, an amino acid substitution at a position corresponding to position 97 in SEQ ID NO: 3, and/or an amino acid substitution at a position corresponding to position 98 in SEQ ID NO: 3.

Embodiment 77. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-76, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) an amino acid substitution at position 5 in SEQ ID NO: 2, an amino acid substitution at position 38 in SEQ ID NO: 2, an amino acid substitution at position 39 in SEQ ID NO: 2, an amino acid substitution at position 97 in SEQ ID NO: 2, and /or amino acid substitution at position 98 in SEQ ID NO: 2; or

b) an amino acid substitution at position 5 in SEQ ID NO: 3, an amino acid substitution at position 38 in SEQ ID NO: 3, an amino acid substitution at position 39 in SEQ ID NO: 3, an amino acid substitution at position 97 in SEQ ID NO: 3, and /or an amino acid substitution at position 98 in SEQ ID NO: 3.

Embodiment 78. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-77, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) proline at a position corresponding to position 5 in SEQ ID NO: 2, glycine at a position corresponding to position 38 in SEQ ID NO: 2, arginine at a position corresponding to position 39 in SEQ ID NO: 2, isoleucine at a position corresponding to 97 in SEQ ID NO: 2, and/or glycine at a position corresponding to position 98 in SEQ ID NO: 2; or

b) proline at a position corresponding to position 5 in SEQ ID NO: 3, glycine at a position corresponding to position 38 in SEQ ID NO: 3, arginine at a position corresponding to position 39 in SEQ ID NO: 3, isoleucine at a position corresponding to 97 in SEQ ID NO: 3, and/or glycine at a position corresponding to position 98 in SEQ ID NO: 3.

Embodiment 79. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-78, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises:

a) proline at position 5 in SEQ ID NO: 2, glycine at position 38 in SEQ ID NO: 2, arginine at position 39 in SEQ ID NO: 2, isoleucine at position 97 in SEQ ID NO: 2 and/or glycine at position 98 of SEQ ID NO: 2; or

b) proline at position 5 in SEQ ID NO: 3, glycine at position 38 in SEQ ID NO: 3, arginine at position 39 in SEQ ID NO: 3, isoleucine at position 97 in SEQ ID NO: 3 and/or glycine at position 98 in SEQ ID NO: 3.

Embodiment 80. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-79, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises at least one additional amino acid modification relative to the wild-type canine IgG-Fc polypeptide and have reduced binding affinity to C1q relative to the wild-type canine IgG-Fc polypeptide.

Embodiment 81. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-80, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises an amino acid substitution at a position corresponding to position 93 in SEQ ID NO: 2, or an amino acid substitution at a position corresponding to position 93 in SEQ ID NO: 3.

Embodiment 82. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-81, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises an amino acid substitution at position 93 in SEQ ID NO: 2, or an amino acid substitution at position 93 in SEQ ID NO: 3.

Embodiment 83. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-82, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises an arginine at a position corresponding to 93 in SEQ ID NO: 2, or arginine at a position corresponding to position 93 in SEQ ID NO: 3.

Embodiment 84. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of Embodiments 42-83, wherein the IgG-Fc polypeptide variant, the first IgG-Fc polypeptide variant, and/or the second IgG-Fc polypeptide variant comprises an arginine at position 93 of SEQ ID NO: 2, or arginine at position 93 in SEQ ID NO: 3.

Embodiment 85. The polypeptide, continuous polypeptide, or heterodimeric protein of any one of embodiments 1-84, wherein the polypeptide is an antibody, fusion antibody, or fusion polypeptide.

Embodiment 86. A continuous polypeptide comprising:

a) the first glucagon-like peptide-1 (GLP1) polypeptide (GLP1A);

b) first linker (L1);

c) Fc polypeptide (Fc) from one companion animal species;

d) optionally, a second linker (L2); And

e) optionally, a second GLP-1 polypeptide (GLP1B).

Embodiment 87. The continuous polypeptide of Embodiment 65, comprising:

formula (I): GLP1A-L1-Fc; or

formula (II): Fc-L1-GLP1A.

Embodiment 88. The continuous polypeptide of Embodiment 65, comprising:

formula (III): GLP1A-L1-Fc-L2-GLP1B.

Embodiment 89. The contiguous polypeptide of any one of embodiments 86-88, wherein GLP1B, if present, contains the same amino acid sequence as GLP1A.

Embodiment 90. A continuous polypeptide comprising:

a) glucagon-like peptide-1 polypeptide (GLP1);

b) first linker (L1);

c) Fc polypeptide (Fc);

d) second linker (L2); And

e) glucagon polypeptide (Gluc).

Embodiment 91. The continuous polypeptide of Embodiment 90, comprising:

formula (IV): GLP1-L1-Fc-L2-Gluc; or

formula (V): Gluc-L1-Fc-L2-GLP1.

Embodiment 92. The continuous polypeptide of any one of embodiments 86-91, wherein GLP1A, GLP-1 and/or GLP1B, if present, comprise a wild-type GLP-1 polypeptide.

Embodiment 93. The continuous polypeptide of any one of embodiments 86-92, wherein GLP1A, GLP1 and/or GLP1B, if present, are a variant of the GLP1 polypeptide.

Embodiment 94. The contiguous polypeptide of any one of Embodiments 86-93, wherein GLP1A, GLP1 and/or GLP1B, if present, comprises the amino acid sequence of SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 98 or SEQ ID NO: 99.

Embodiment 95. The continuous polypeptide of any one of Embodiments 86-94, wherein the glucagon polypeptide comprises a wild-type glucagon polypeptide, optionally comprising the amino acid sequence of SEQ ID NO: 21.

Embodiment 96. The continuous polypeptide of any one of Embodiments 86-95, wherein the glucagon polypeptide is a variant of the glucagon polypeptide.

Embodiment 97. The continuous polypeptide of any one of Embodiments 86-96, wherein the Fc polypeptide is a human IgG-Fc.

Embodiment 98. The continuous polypeptide of any one of Embodiments 86-97, wherein the Fc polypeptide is a human IgG1-Fc, IgG2-Fc, IgG3-Fc, or IgG4-Fc.

Embodiment 99. The contiguous polypeptide of any one of embodiments 86-98, wherein the Fc polypeptide is an Fc region from one companion animal species.

Embodiment 100. The continuous polypeptide of any one of Embodiments 86-97 or 99, wherein the Fc polypeptide comprises:

a) canine IgG-A-Fc, IgG-B-Fc, IgG-C-Fc or IgG-D-Fc;

b) equine IgG1-Fc, IgG2-Fc, IgG3-Fc, IgG4-Fc, IgG5-Fc, IgG6-Fc or IgG7-Fc; or

c) Feline IgG1a-Fc, IgG1b-Fc or IgG2-Fc.

Embodiment 101. The contiguous polypeptide of any one of embodiments 86 to 100, wherein the polypeptide is a wild type IgG Fc polypeptide.

Embodiment 102. The continuous polypeptide of any one of embodiments 86-100, wherein the Fc polypeptide is a variant of an IgG-Fc polypeptide.

Embodiment 103. The continuous polypeptide of any one of embodiments 86-102, wherein the polypeptide comprises an Fc polypeptide, a continuous polypeptide, or a heterodimeric protein of any of embodiments 1-84.

Embodiment 104. The continuous polypeptide of any one of embodiments 85-102, wherein the continuous polypeptide has a longer serum half-life than the wild-type GLP1 polypeptide.

Embodiment 105. The contiguous polypeptide of any one of embodiments 86-104, wherein L1 and L2, if present, each independently constitute a flexible linker.

Embodiment 106. The contiguous polypeptide of any one of embodiments 86-105, wherein the amino acid sequences L1 and L2, if present, each independently comprise 100%, at least 95%, at least 90%, at least 85 % amino acid residues of serine and/or glycine.

Embodiment 107. The continuous polypeptide of any one of embodiments 86-106, wherein the continuous polypeptide is extended at its C-terminus.

Embodiment 108. The continuous polypeptide of any one of embodiments 86-107, wherein the continuous polypeptide comprises a glycine residue, two glycine residues, three glycine residues, four glycine residues, five glycine residues, six glycine residues, seven glycine residues, eight glycine residues or more than eight glycine residues at the C-terminus.

Embodiment 109. The contiguous polypeptide of any one of embodiments 86-108, wherein the contiguous polypeptide comprises the amino acid sequence of SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94 or SEQ ID NO: 95 at its C-terminus.

Embodiment 110. The continuous polypeptide of any one of embodiments 86-109, wherein the continuous polypeptide comprises:

a) amino acid sequence SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 27; SEQ ID NO: 28; SEQ ID NO: 29; SEQ ID NO: 30; SEQ ID NO: 31; SEQ ID NO: 32; SEQ ID NO: 33; SEQ ID NO: 34; SEQ ID NO: 35; SEQ ID NO: 36; SEQ ID NO: 37; SEQ ID NO: 38; SEQ ID NO: 39; SEQ ID NO: 40; SEQ ID NO: 41; SEQ ID NO: 42; SEQ ID NO: 43; SEQ ID NO: 44; SEQ ID NO: 45; SEQ ID NO: 46; SEQ ID NO: 47, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105 or SEQ ID NO: 10; or

b) amino acid sequence SEQ ID NO: 52; SEQ ID NO: 53; SEQ ID NO: 54; SEQ ID NO: 55; SEQ ID NO: 56; SEQ ID NO: 57; SEQ ID NO: 58 or SEQ ID NO: 59.

Embodiment 111. A polypeptide comprising the amino acid sequence of SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 27; SEQ ID NO: 28; SEQ ID NO: 29; SEQ ID NO: 30; SEQ ID NO: 31; SEQ ID NO: 32; SEQ ID NO: 33; SEQ ID NO: 34; SEQ ID NO: 35; SEQ ID NO: 36; SEQ ID NO: 37; SEQ ID NO: 38; SEQ ID NO: 39; SEQ ID NO: 40; SEQ ID NO: 41; SEQ ID NO: 42; SEQ ID NO: 43; SEQ ID NO: 44; SEQ ID NO: 45; SEQ ID NO: 46; SEQ ID NO: 47, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 52; SEQ ID NO: 53; SEQ ID NO: 54; SEQ ID NO: 55; SEQ ID NO: 56; SEQ ID NO: 57; SEQ ID NO: 58; SEQ ID NO: 59; SEQ ID NO: 103; SEQ ID NO: 104, SEQ ID NO: 105 or SEQ ID NO: 106.

Embodiment 112. The polypeptide, heterodimeric protein, or continuous polypeptide of any of the preceding embodiments, wherein at least one amino acid modification or substitution comprises an amino acid substitution of an amino acid derivative.

Embodiment 113. An isolated nucleic acid encoding a polypeptide, heterodimeric protein, or continuous polypeptide according to any of the preceding embodiments.

Embodiment 114. A host cell containing the nucleic acid of embodiment 113.

Embodiment 115. A method for producing a polypeptide, comprising culturing a host cell as in embodiment 114 and isolating the polypeptide.

Embodiment 116. A pharmaceutical composition comprising the polypeptide, heterodimeric protein, or continuous polypeptide of any one of embodiments 1-112 and a pharmaceutically acceptable carrier.

Embodiment 117. A method for increasing cAMP production in a cell, the method comprising exposing the cell to a polypeptide, heterodimeric protein, continuous polypeptide or pharmaceutical composition according to any one of embodiments 1-112 or 116 under conditions allowing binding of the polypeptide, heterodimeric protein or continuous polypeptide with GLP1R.

Embodiment 118. The method of Embodiment 117, wherein the cell is exposed to a polypeptide, heterodimeric protein, continuous polypeptide, or pharmaceutical composition ex vivo.

Embodiment 119. The method of Embodiment 117, wherein the cell is exposed to the polypeptide, heterodimeric protein, continuous polypeptide, or pharmaceutical composition in vivo.

Embodiment 120. The method of any one of embodiments 118-119, wherein the cell is a human cell, a canine cell, a feline cell, or an equine cell.

Embodiment 121. A method of delivering a polypeptide to a subject, comprising administering the polypeptide, heterodimeric protein, continuous polypeptide, or pharmaceutical composition of any one of embodiments 1-112 or 116 parenterally.

Embodiment 122. A method of delivering a polypeptide to a subject, comprising administering the polypeptide, heterodimeric protein, continuous polypeptide, or pharmaceutical composition of any one of Embodiments 1-112 or 116 by the intramuscular route, the intraperitoneal route, the intracerebrospinal route, the subcutaneous route, the intra-arterial route, the intra-articular route. route, intrathecal route or inhalation route.

Embodiment 123. A method of treating a subject having diabetes or obesity, the method comprising administering to the subject a therapeutically effective amount of a polypeptide, heterodimeric protein, continuous polypeptide, or pharmaceutical composition of any one of embodiments 1-112 or 116.

Embodiment 124. The method of Embodiment 123, comprising administering insulin, a DPP4 inhibitor, an SGLT2 inhibitor, biguanides, sulfonylureas, meglitinide derivatives, an alpha-glucosidase inhibitor, a thiazolidinedione (TZD), an amylinomimetic, a bile acid sequestrant, a dopamine agonist.

Embodiment 125. The method of any one of embodiments 121-124, wherein the subject is a human.

Embodiment 126. The method of any one of embodiments 121-124, wherein the subject is a companion animal.

Embodiment 127. The method of embodiment 126, wherein the companion animal is a feline, canine, or equine.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1 shows a sequence alignment of the Fc regions of IgG-A, B, C and D in canines. The box contains areas likely to be in contact with protein A.

[0007] Figure 2A shows the SDS-PAGE separation of the polypeptides GLP1-G8/GLP-2G_III_WTfeIgG2 (SEQ ID NO: 23; “GLP1A variant” in this figure) and GLP1-G8_I_WTfeIgG2 (SEQ ID NO: 24; “GLP1B variant” " in this figure) having a wild-type feline IgG2 hinge region with a single disulfide bond, in the absence and presence of a reducing agent (DTT).

[0008] Figure 2B shows the SDS-PAGE separation of the polypeptides GLP1-G8/GLP-2G_III_VARfeIgG2 (SEQ ID NO: 25; “GLP1 MA variant” in this figure) and GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26; “variant GLP1 MB" in this figure) having a variant feline IgG2 hinge region with two disulfide bonds, in the absence and presence of a reducing agent (DTT).

[0009] Figure 3 shows the results of the CHO-K1 GLP1R cAMP kit assay to evaluate the activity of GLP1-G8/GLP1-2G_III_VARfeIgG2 (SEQ ID NO: 25) and GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) compared to control samples (GLP1 (7-37) and Extendin-4).

[0010] Figure 4 shows the results of a cell-based assay to evaluate the activity of GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) (“GLP1-B” in this figure) after 1 year of storage using CHOK1-GLP1R cells and the cAMP-glo kit ( n=2).

[0011] Figure 5 shows the result of immunoblotting analysis for GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) (“GLP1B” in this figure) after incubation in serum for 24 hours at 37°C (lane 1), in PBS at for 24 hours at 37°C (lane 2), in PBS for 24 hours at 4°C (lane 9). Mouse anti-GLP1 antibodies were used.

[0012] Figure 6 is a plot of GLP1-G8_I_VARfeIgG2 (SEQ ID NO:26) serum concentration versus time following subcutaneous administration to 5 cats as measured by quantitative ELISA.

[0013] Figure 7 is a graph of GLP1-G8_I_VARfeIgG2 (SEQ ID NO:26) serum concentration versus time after subcutaneous administration to 5 cats as measured by a cellular activity assay. The mean AUC from 0 to 168 hours was approximately 840 mcg(h)/mL, and the mean t1 _/2 was 36 hours.

DESCRIPTION OF SEQUENCES

[0014] Table 1 provides a list of example sequences provided herein.

Table 1: sequence descriptions SEQ ID NO: SUBSEQUENCE DESCRIPTION 1 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSVDK SRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of wild type canine IgG-A-Fc
Protein A -
C1q-
CD16- 2 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSR WQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of wild type canine IgG-B-Fc
Protein A+
C1q+
CD16+ 107 PKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of wild type canine IgG-B-Fc with hinge region
Protein A+
C1q+
CD16+ 3 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of wild type canine IgG-C-Fc
Protein A -
C1q+
CD16+ 108 AKECECKCNCNNCPCPGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSY FLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of wild type canine IgG-C-Fc with hinge region
Protein A -
C1q+
CD16+ 4 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVD KSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of wild type canine IgG-D-Fc
Protein A -
C1q-
CD16- 5 PVPEPLGGPSVLIFPPKPKD T L L I A RTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPI G HQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSK LSVDKSRWQQGDPFTCAVMHE A L H NHYTDLSLSHSPGK Example of a canine IgG-A-Fc variant
C1q-
Protein A+
I(21)T
R(23)L
T(25)A
E(80)G
T(205)A
Q(207)H 6 PGCGLLGGPSVFIFPPKPKD T L LI ARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLS VDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
C1q+
Protein A+
I(21)T
V(23)L
T(24)I 7 PVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYS KLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGK Example of a canine IgG-D-Fc variant
C1q-
Protein A+
I(21)T
R(23)L
T(25)A
E(80)G
Q(207)H 8 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPPSPKELSSSDTVSI Y CLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSVD KSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of a canine IgG-A-Fc variant
Heterodimeric chain 1 T(138)Y 9 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFL T SKLSVDK SRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of a canine IgG-A-Fc variant
Heterodimeric chain 2
Y(181)T 10 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSL Y CLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Heterodimeric chain 1 T(137)Y eleven PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL T SKLSVDKSR WQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Heterodimeric chain 2
Y(180)T 12 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTL Y CLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Heterodimeric chain 1 T(137)Y 13 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFL T SKLSVD KSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Heterodimeric chain 2
Y(180)T 14 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTL Y CLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSV DKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of a canine IgG-D-Fc variant
Heterodimeric chain 1 T(138)Y 15 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFL T SKLSVD KSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of a canine IgG-D-Fc variant
Heterodimeric chain 2
Y(181)T 109 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPPSPKELSSSDTVSI W CLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSVD KSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of a canine IgG-A-Fc variant
Heterodimeric chain 3
T(138)W 110 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPPSPKELSSSDTVSI S C A IKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFL T SKLSV DKSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of a canine IgG-A-Fc variant
Heterodimeric chain 4
T(138)S
L(140)A
Y(181)T 111 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSL W CLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Heterodimeric chain 3
T(137)W 112 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSL S C A IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL T SKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Heterodimeric chain 4
T(137)S
L(139)A
Y(180)T 113 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTL W CLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Heterodimeric chain 3
T(137)W 114 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTL S C A VKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFL T SKLS VDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Heterodimeric chain 4
T(137)S
L(139)A
Y(180)T 115 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTL W CLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSV DKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of a canine IgG-D-Fc variant
Heterodimeric chain 3
T(138)W 116 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTL S C A IKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFL T SKLS VDKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of a canine IgG-D-Fc variant
Heterodimeric chain 4
T(138)S
L(140)A
Y(181)T 16 PKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYF LYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of wild type feline IgG2-Fc
Protein A+
C1q- 117 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDG TYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of wild type feline IgG1a-Fc
Protein A+
C1q+ 118 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQLDSD GTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of wild type feline IgG1b-Fc
Protein A+
C1q+ 119 PKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSV W CLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTY FLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG2-Fc variant
Heterodimeric chain 1
T(154)W 120 PKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSV S C A IKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDG TYFL T SRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG2-Fc variant
Heterodimeric chain 2
T(154)S
L(156)A
Y(197)T 121 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSV W CLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSD GTYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1a-Fc variant
Heterodimeric chain 1
T(154)W 122 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSV S C A IKSFHPPDIAVEWEITGQPEPENNYRTTPPQLD SDGTYFV T SKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1a-Fc variant
Heterodimeric chain 2
T(154)S
L(156)A
Y(197)T 123 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSV W CLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQLD SDGTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1b-Fc variant
Heterodimeric chain 1
T(154)W 124 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSV S C A IEGFYPSDIAVEWEITGQPEPENNYRTTPPQ LDSDGTYFL T SRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1b-Fc variant
Heterodimeric chain 2
T(154)S
L(156)A
Y(197)T 17 PKTASTIESKTGE C PKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTY FLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG2-Fc variant
Hinge Cys
G(14)C 125 RKTDHPPGPKPCDCPKCPPPEMLGGP SVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDG TYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG2-Fc variant with a feline IgG1 hinge region 126 PKTASTIESKTGEGP P CPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYF LYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG2-Fc variant with a modified hinge region
K(16)P 127 RKTDHPPGPKPCDCP P CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDG TYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1a-Fc variant with a modified hinge region
K(16)P 128 RKTDHPPGPKPCDCP P CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQLDSD GTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1b-Fc variant with a modified hinge region
K(16)P 18 DMSKCPKCPAPELL GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSK LSLETSRWQQVESFTCAVMHEALHNHFTKTDISESLGK Example of equine IgG2-Fc variant (with equine IgG1 hinge region)
Protein A -
C1q- 19 DMSKCPKCPAPELL GGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLY SKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK Example of equine IgG2-Fc variant (with equine IgG1 hinge region)
C1q-
Protein A+
A(29)T
F(217)Y 20 H X EGTFTSDVSSYLEGQAAKEFIAWLVKG Example of GLP1 variant (7-35)
X8 can be G or S 21 HSQGTFTSDYSKYLDSRRAQDFVQWLMNT Glucagon (Gluc) 22 HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS Extendin-4 23 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENK VSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG GLP1-G8/GLP-2G_III_WTfeIgG2 24 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENK VSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK GLP1-G8_I_WTfeIgG2 25 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGE C PKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSEN KVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG GLP1-G8/GLP1-2G_III_ VARfeIgG2 26 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGE C PKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSEN KVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK GLP1-G8_I_VARfeIgG2 27 H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENK VSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG GLP1-S8/GLP1-3G_III_WTfeIgG2 28 H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENK VSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK GLP1-S8_I_WTfeIgG2 29 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKESTSKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSP KELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG GLP1-G8/GLP1-3G_III_ VARcaIgGD thirty H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKESTCKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSPK ELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGK GLP1-G8_I_VARcaIgGD 31 H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKESTSKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSP KELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG GLP1-S8/GLP1-3G_III_ VARcaIgGD 32 H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKESTCKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSPK ELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGK GLP1-S8_I_VARcaIgGD 33 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPSVPDELAKSKV TCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG GLP1-G8/GLPL1-3G_III_VAReqIgG2 34 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPSVPDELAKSKV TCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK GLP1-G8_I_VAReqIgG2 35 H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPSVPDELAKSKV TCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG GLP1-S8/GLP1-3G_III_VAReqIgG2 36 H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPSVPDELAKSKV TCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK GLP1-S8_I_VAReqIgG2 37 MAVLGLLFCLVTFPSCVLS H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEP QVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG ssGLP1-S8/GLP1-3G_III_WTfeIgG2 38 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGE C PKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPH EPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG ssGLP1-G8/GLP1-2G_III_ VARfeIgG2 39 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGE C PKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPH EPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK ssGLP1-G8_I_VARfeIgG2 40 MAVLGLLFCLVTFPSCVLS H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEP QVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK ssGLP1-S8_I_WTfeIgG2 41 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKESTCKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARG QAHQPSVYVLPPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG ssGLP1-G8/GLP1-2G_III_ VARcaIgGD 42 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKEST S KCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKA RGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG ssGLP1-G8/GLP1-2G_III_ VARcaIgGD 43 MAVLGLLFCLVTFPSCVLS H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKEST S KCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKA RGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG ssGLP1-S8/GLP1-3G_III_ VARcaIgGD 44 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQV YVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG ssGLP1-G8/GLP1-3G_III_VAReqIgG2 45 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSSVPKPQCPPYTHSKFLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGP SRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK ssGLP1-G8_I_VAReqIgG2 46 MAVLGLLFCLVTFPSCVLS H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQV YVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG ssGLP1-S8/GLP1-3G_III_VAReqIgG2 47 MAVLGLLFCLVTFPSCVLS H S EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSSVPKPQCPPYTHSKFLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGP SRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK ssGLP1-S8_I_VAReqIgG2 48 MGLVAPVVLLHQDDEEHGQDEGPEDGSGYLLGTLTRFSSDFDSAPEVILAPDDQLQLPHPSSRENFWARTGLCAESFLLRPVGPVGPVMGWSEGFHKRNSRQEFLRRRLFAGGLCAASTQESRNRCSSRGCKSSPADCPELDRTQHLGNSVGPIQAAHQELALGAGGPGDECQCCSVSNSLFIPEPQSTCPYNGYTSWPLEGNLRVACAPPPP PPARTLFGGSRRGAVDKKAGGGNRSPGGGAGTGEFGAPGAGGGLGRRPEVGAWTAAEGTNPADLASSPPPPSTRPPAAPRPPCADFCAASPQTTFPTPSPR RPLPASGGATVSLSETVQKWREYRHQCQRFLTEAPPPATGLFCNRTFDEYACWPDGLPGSFVNVSCPWYLPWASSVLQGHVYRFCTAEGLWLRQDNSSLPWRNLSECEESKRGERSSPEEQLLSFS IIYTVGYTLSFSALVIASAILLSFRHLHCTRNYIHLNLFASFILRALSVFIRDAVLKWMYSTAPQQHQWDGLLSYQDSLGCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCR LAKSTLTLIPLLGTHEVVFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQMEFRRSWERWRLKHLHIQRDSSMKPLKCPTSSLTSGGTVGSSVYAASCQASCS Feline glucagon-like peptide 1 receptor (GLP1R) 49 RPLPASGGATVSLSETVQKWREYRHQCQRFLTEAPPPATGLFCNRTFDEYACWPDGLPGSFVNVSCPWYLPWASSVLQGHVYRFCTAEGLWLRQDNSSLPWRNLSECEESKRGERSSPEEQLLSFS N-terminal domain of the mature feline glucagon-like peptide 1 receptor (GLP1R-N) 50 METDTLLLWVLLLWVPGSTG RPLPASGGATVSLSETVQKWREYRHQCQRFLTEAPPPATGLFCNRTFDEYACWPDGLPGSFVNVSCPWYLPWASSVLQGHVYRFCTAEGLWLRQDNSSLPWRNLSECEESKRGERSSPEEQLLSFSGSENLYFQGPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKHHHHHH ssFeGLP1R-N_huFc_ PolyHis 51 METDTLLLWVLLLWVPGSTG RPLPASGGATVSLSETVQKWREYRHQCQRFLTEAPPPATGLFCNRTFDEYACWPDGLPGSFVNVSCPWYLPWASSVLQGHVYRFCTAEGLWLRQDNSSLPWRNLSECEESKRGERSSPEEQLLSFSGGGSHHHHHH ssFeGLP1R-N_PolyHis 52 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENK VSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHSQGTFTSDYSKYLDSRRAQDFVQWLMNTGGG GLP1-G8/Gluc-3G_IV_WTfeIgG2 53 HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGGGGSGGGGSGGGGSGGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEE LSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG Gluc/GLP1-2G_V_WTfeIgG2 54 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKEST S KCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSP KELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHSQGTFTSDYSKYLDSRRAQDFVQWLMNTGGGG GLP1-G8/Glu-4G_IV_ VARcaIgGD 55 HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGAGGGGGSGGGSGGGSGGSPKEST S KCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYV LPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG Gluc/GLP1-3G_V_ VARcaIgGD 56 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPSVPDELAKSKV TCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHSQGTFTSDYSKYLDSRRAQDFVQWLMNTGGGG GLP1-G8/Gluc-4G_IV_VAReqIgGD 57 HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKS KVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG Gluc/GLP1-3G_V_VAReqIgG2 58 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGHSQGTFTSDYSKYLDSRRAQDFVQWLMNTGGGG GLP1-G8/Glu-4G_IV_huIgG4 59 HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGGGGGSGGGSGGGSGGGSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLP PSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGG Gluc/GLP1-3G_V_huIgG4 60 PVPEPLGGPSVLIFPPKPKD T LRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSV DKSRWQQGDPFTCAVMHETL H NHYTDLSLSHSPGK Example of a canine IgG-A-Fc variant
C1q-
Protein A+
I(21)T
Q(207)H 61 PGCGLLGGPSVFIFPPKPKD T LVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
C1q+
Protein A+
I(21)T 62 PVPESLGGPSVFIFPPKPKD T LRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLS VDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGK Example of a canine IgG-D-Fc variant
C1q-
Protein A+
I(21)T
Q(207)H 63 GGPSVFLFPPNPKDTLMITRTPEVTCVVVDVSQENPDVKFNWYMDGVEVRTATTRPKEEQFNSTYRVVSVLRIQHQDWLSGKEFKCKVNNQALPQPIERTITKTKGRSQEPQVYVLAPHPDESKKSKVSVTCLVKDFYPPEINIEWQSNGQPELETKYSTTQAQQDSDGSYFLYSKLSVDR NRWQQGTTFTCGVMHEALHNHYTQKNVSKNPGK Example of wild type equine IgG1-Fc
Protein A+
C1q+ 64 GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVE SFTCAVMHEALHNHFTKTDISESLGK Example of wild type equine IgG2-Fc
Protein A -
C1q- 65 GGPSVFIFPPKPKDVLMITRMPEVTCLVVDVSHDSSDVLFTWYVDGTEVKTAKTMPNEEQNNSTYRVVSVLRIQHQDWLNGKKFKCKVNNQALPAPVERTISKATGQTRVPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDITVEWQSNEHPEPEGKYRTTEAQKDSDGSYFLYSKLTVEKDRWQQG TTFTCVVMHEALHNHVMQKNISKNPGK Example of wild type equine IgG3-Fc
Protein A+
C1q+ 66 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQFNSTYRVVSVLPIQHKDWLSGKEFKCKVNNKALPAPVERTISAPTGQPREPQVYVLAPHRDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDSDGSYFLYSKLTVETNRWQQGTT FTCAVMHEALHNHYTEKSVSKSPGK Example of wild type equine IgG4-Fc
Protein A+
C1q+ 67 GGPSVFIFPPKPKDVLMISRKPEVTCVVVDLGHDDPDVQFTWFVDGVETHTATTEPKEEQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTSKALPAPVERTISKAKGQLRVPQVYVLAPHPDELAKNTVSVTCLVKDFYPPEIDVEWQSNEHPEPEGKYSTTTPAQLNSDGSYFLYSKLSVETSRWKQ GESFTCGVMHEAVENHYTQKNVSHSPGK Example of wild type equine IgG5-Fc
Protein A -
C1q- 68 GRPSVFIFPPNPKDTLMISRTPEVTCVVVDVSQENPDVKFNWYVDGVEAHTATTKAKEKQDNSTYRVVSVLPIQHQDWRRGKEFKCKVNNRALPAPVERTITKAKGELQDPQVYILAPHPDEVTKNTVSVTCLVKDFYPPDINVEWQSNEEPEPEVKYSTTPAQLDGDGSYFLYSKLTVETDRWEQGESFT CVVMHEAIRHTYRQKSITNFPGK Example of wild type equine IgG6-Fc
Protein A -
C1q- 69 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQNNSTYRVVSILAIQHKDWLSGKEFKCKVNNQALPAPVQKTISKPTGQPREPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDGDGSYFLYSKLTVETNRW QQGTTFTCAVMHEALHNHYTEKSVSKSPGK Example of wild type equine IgG7-Fc
Protein A+
C1q+ 70 GGPSVFLFPPNPKDTLMITRTPEVTCVVVDVSQENPDVKFNWYMDGVEVRTATTRPKEEQFNSTYRVVSVLRIQHQDWLSGKEFKC S VNNQALPQPIERTITKTKGRSQEPQVYVLAPHPDESKKSKVSVTCLVKDFYPPEINIEWQSNGQPELETKYSTTQAQQDSDGSYFLYSKLSV DRNRWQQGTTFTCGVMHEALHNHYTQKNVSKNPGK Example of equine IgG1-Fc variant
Protein A+
C1q-
K(87)S 71 GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQG ESFTCAVMHEALHNH Y TKTDISESLGK Example of equine IgG2-Fc variant
C1q-
Protein A+
F(203)Y 72 GGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQ QVESFTCAVMHEALHNH Y TKTDISESLGK Example of equine IgG2-Fc variant
C1q-
Protein A+
A(15)T
F(203)Y 129 PPCVLSAEGVIPIPSVPKPQCPPYTHSKFL GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYS TTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNHFTKTDISESLGK Example of wild type equine IgG2-Fc with hinge region
Protein A -
C1q- 130 PPCVLSAEGVIPIPSVPKPPCPPYTHSKFL GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTT PAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNHFTKTDISESLGK Example of an equine IgG2-Fc variant with a modified hinge region
Protein A -
C1q-
Q(20)P 131 PPSVLSAEGVIPIPSVPKPQCPPYTHSKFL GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYS TTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNHFTKTDISESLGK Example of an equine IgG2-Fc variant with a modified hinge region
Protein A -
C1q-
C(3)S 132 PPSVLSAEGVIPIPSVPKPPCPPYTHSKFL GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTT PAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNHFTKTDISESLGK Example of an equine IgG2-Fc variant with a modified hinge region
Protein A -
C1q-
C(3)S
Q(20)P 133 PPCVLSAEGVIPIPSVPKPQCPPYTHSKFL GGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGK YSTTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK Example of an equine IgG2-Fc variant with a hinge region
Protein A+
C1q-
A(45)T
F(233)Y 134 PPCVLSAEGVIPIPSVPKPPCPPYTHSKFL GGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKY STTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK Example of an equine IgG2-Fc variant with a modified hinge region
Protein A+
C1q-
Q(20)P
A(45)T
F(233)Y 135 PPSVLSAEGVIPIPSVPKPPCPPYTHSKFL GGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKY STTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK Example of an equine IgG2-Fc variant with a modified hinge region
Protein A+
C1q-
C(3)S
Q(20)P
A(45)T
F(233)Y 73 GGPSVFIFPPKPKDVLMITRMPEVTCLVVDVSHDSSDVLFTWYVDGTEVKTAKTMPNEEQNNSTYRVVSVLRIQHQDWLNGKKFKC S VNNQALPAPVERTISKATGQTRVPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDITVEWQSNEHPEPEGKYRTTEAQKDSDGSYFLYSKLTVEKDRWQQ GTTFTCVVMHEALHNHVMQKNISKNPGK Example of equine IgG3-Fc variant
Protein A+
C1q-
K(87)S 74 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQFNSTYRVVSVLPIQHKDWLSGKEFKC S VNNKALPAPVERTISAPTGQPREPQVYVLAPHRDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDSDGSYFLYSKLTVETNRWQQG TTFTCAVMHEALHNHYTEKSVSKSPGK Example of equine IgG4-Fc variant
Protein A+
C1q-
K(87)S 75 GGPSVFIFPPKPKDVLMISRKPEVTCVVVDLGHDDPDVQFTWFVDGVETHTATTEPKEEQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTSKALPAPVERTISKAKGQLRVPQVYVLAPHPDELAKNTVSVTCLVKDFYPPEIDVEWQSNEHPEPEGKYSTTTPAQLNSDGSYFLYSKLSVETSRWKQ GESFTCGVMHEA LH NHYTQKNVSHSPGK Example of equine IgG5-Fc variant
C1q-
Protein A+
V(199)L
E(200)H 76 GRPSVFIFPPNPKDTLMISRTPEVTCVVVDVSQENPDVKFNWYVDGVEAHTATTKAKEKQDNSTYRVVSVLPIQHQDWRRGKEFKCKVNNRALPAPVERTITKAKGELQDPQVYILAPHPDEVTKNTVSVTCLVKDFYPPDINVEWQSNEEPEPEVKYSTTPAQLDGDGSYFLYSKLTVETDRWEQGESFT CVVMHEA LHNH YRQKSITNFPGK Example of equine IgG6-Fc variant
C1q-
Protein A+
I(199)L
R(200)H
H(201)N
T(202)H 77 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQNNSTYRVVSILAIQHKDWLSGKEFKC S VNNQALPAPVQKTISKPTGQPREPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDGDGSYFLYSKLTVETNR WQQGTTFTCAVMHEALHNHYTEKSVSKSPGK Example of equine IgG7-Fc variant
Protein A+
C1q-
K(87)S 78 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTC R VNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q-
K(93)R 79 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKC R VNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A -
C1q-
K(93)R 80 RKTDDHPPGPKTGEGPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDG TYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of wild type feline IgG1a-Fc
Protein A+
C1q+ 81 RKTDHPPGPKTGEGPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQLDSD GTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of wild type feline IgG1b-Fc
Protein A+
C1q+ 136 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPS P IERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLD SDGTYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1a-Fc variant
Protein A+
C1q-
P(198)A 82 RKTDHPPGPKTGEGPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPS P IERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLD SDGTYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1a-Fc variant
Protein A+
C1q-
P(198)A 137 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPS P IERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQ LDSDGTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1b-Fc variant
Protein A+
C1q-
P(198)A 83 RKTDDHPPGPKTGEGPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPS P IERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQ LDSDGTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of a feline IgG1b-Fc variant
Protein A+
C1q-
P(198)A 84 PGCGLLGGPSVFIFPPKPKD T L LI ARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKC R VNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
C1q-
K(93)R
Protein A+
I(21)T
V(23)L
T(24)I 85 HAEGTFTSDVSSYLEGQAAKEFIAWLVKGAG GLP1(7-37) wild type 86 H S EGTFTSDVSSYLEGQAAKEFIAWLVKG GLP1-S8 (7-35) 87 H G EGTFTSDVSSYLEGQAAKEFIAWLVKG GLP1-G8 (7-35) 88 G 1G extension 89 GG 2G extension 90 GGG 3G extension 91 GGGG 4G extension 92 GGGGG 5G extension 93 GGGGGG 6G extension 94 GGGGGGG 7G extension 95 GGGGGGGG 8G extension 96 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEP QVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK ssGLP1-G8_I_WTfeIgG2 97 MAVLGLLFCLVTFPSCVLS H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSPKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEP QVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG ssGLP1-G8/GLP1-3G_III_WTfeIgG2 98 HAEGTFTSDVSSYLEGQAAKEFIAWLVKGA GLP1 variant (7-36) 99 HAEGTFTSDVSSYLEGQAAKEFIAWLVKG GLP1 variant (7-35) 100 VPKPQCPPYTHSKFL GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSY FLYSKLSLETSRWQQVESFTCAVMHEALHNHFTKTDISESLGK Example of wild-type equine IgG2-Fc (including the equine IgG2 hinge region)
Protein A -
C1q- 101 DMSKCPKCPAPELL Example of a wild-type equine IgG1 hinge region 102 VPKPQCPPYTHSKFL Example of a wild-type equine IgG2 hinge region 138 PPCVLSAEGVIPIPS VPKPQCPPYTHSKFL Example of a wild-type equine IgG2 hinge region 103 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSDMSKCPKCPAPELLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPSVPDELAKSKV TCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGGG GLP1-G8/GLP1-3G_III_VAReqIgG2 104 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGAGGGGGSGGGSGGGSGGGSSVPKPQCPPYTHSKFLGGPSVFIFPPNPKD T LMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELA KSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNH Y TKTDISESLGK GLP1-G8_I_VAReqIgG2 105 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKESTCKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSPK ELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG GLP1-G8/GLP1-2G_III_ VARcaIgGD 106 H G EGTFTSDVSSYLEGQAAKEFIAWLVKGGGGSGGGGSGGGGSGGGGSPKESTSKCISPCPVPESLGGPSVFIFPPKPKD T L L I A RTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSTYRVVSVLPI G HQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPPSP KELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEAL H NHYTDLSLSHSPGKGGGGSGGGGHAEGTFTSDVSSYLEGQAAKEFIAWLVKGGG GLP1-G8/GLP1-2G_III_ VARcaIgGD 139 PAPE P LGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
M(5)P 140 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLD R EDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
P(39)R 141 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDL G PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
D(38)G 142 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNN I ALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
K(97)I 143 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNK G LPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
A(98)G 144 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDL G PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNN IG LPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
D(38)G
K(97)I
A(98)G 145 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDL G PEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTC R VNN IG LPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLS VDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q-
CD16-
D(38)G
K(93)R
K(97)I
A(98)G 146 PAPE P LGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLD R EDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q+
CD16-
M(5)P
P(39)R 147 PAPE P LGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLD R EDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTC R VNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of a canine IgG-B-Fc variant
Protein A+
C1q-
CD16-
M(5)P
P(39)R
K(93)R 148 PGCG P LGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
L(5)P 149 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLD R ENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
P(39)R 150 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDL G PENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
D(38)G 151 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDL D PENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNN I ALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
K(97)I 152 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDL D PENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNK G LPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLS VDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
A(98)G 153 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKC R VNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q-
CD16+
K(93)R 154 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDL G PENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNN IG LPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLS VDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
D(38)G
K(97)I
A(98)G 155 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDL G PENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKC R VNN IG LPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q-
CD16-
D(38)G
K(93)R
K(97)I
A(98)G 156 PGCG P LGGPSVFIFPPKPKDILVTARTPTVTCVVVDLD R ENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLS VDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q+
CD16-
L(5)P
P(39)R 157 PGCG P LGGPSVFIFPPKPKDILVTARTPTVTCVVVDLD R ENPEVQISWFVDSKQVQTANTQPREEQSNGTYRVVSVLPIGHQDWLSGKQFKC R VNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of a canine IgG-C-Fc variant
Protein A+
C1q-
CD16-
M(5)P
P(39)R
K(93)R 158 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFX ₁ GTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSV DKSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of an aglycosylated variant of canine IgG-A-Fc
N(68)X ₁
X ₁ = any amino acid except N 159 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFN P TYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSV DKSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of an aglycosylated variant of canine IgG-A-Fc
G(69)P 160 PVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQSREQQFNGX ₂ YRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLS VDKSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Example of an aglycosylated variant of canine IgG-A-Fc
T(70) _X2
X ₂ = any amino acid except T or S 161 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFX ₁ GTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of an aglycosylated variant of canine IgG-B-Fc
N(68)X ₁
X ₁ = any amino acid except N 162 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFN P TYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of an aglycosylated variant of canine IgG-B-Fc
G(69)P 163 PAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGX ₂ YRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Example of an aglycosylated variant of canine IgG-B-Fc
T(70) _X2
X ₂ = any amino acid except T or S 164 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSX ₁ GTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLS VDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of an aglycosylated variant of canine IgG-C-Fc
N(68)X ₁
X ₁ = any amino acid except N 165 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSN P TYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSV DKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of an aglycosylated variant of canine IgG-C-Fc
G(69)P 166 PGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANTQPREEQSNGX ₂ YRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Example of an aglycosylated variant of canine IgG-C-Fc
T(70) _X2
X ₂ = any amino acid except T or S 167 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFX ₁ STYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLS VDKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of an aglycosylated variant of canine IgG-D-Fc
N(68)X ₁
X ₁ = any amino acid except N 168 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFN P TYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLS VDKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of an aglycosylated variant of canine IgG-D-Fc
S(69)P 169 PVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQPREQQFNSX ₂ YRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSK LSVDKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Example of an aglycosylated variant of canine IgG-D-Fc
T(70) _X2
X ₂ = any amino acid except T or S 170 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFX ₁ STYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLD SDGTYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG1a-Fc
N(85)X ₁
X ₁ = any amino acid except N 171 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFN P TYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLD SDGTYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG1a-Fc
S(86)P 172 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSX ₂ YRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKGQPHEPQVYVLPPAQEELSENKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQ LDSDGTYFVYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG1a-Fc
T(87) _X2
X ₂ = any amino acid except T or S 173 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFX ₁ STYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQ LDSDGTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG1b-Fc
N(85)X ₁
X ₁ = any amino acid except N 174 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFN P TYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPPQ LDSDGTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG1b-Fc
S(86)P 175 RKTDHPPGPKPCDCPKCPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSX ₂ YRVVSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKDKGQPHEPQVYVLPPAQEELSENKVSVTCLIEGFYPSDIAVEWEITGQPEPENNYRTTPP QLDSDGTYFLYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG1b-Fc
T(87) _X2
X ₂ = any amino acid except T or S 176 PKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFX ₁ STYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDG TYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG2-Fc
N(85)X ₁
X ₁ = any amino acid except N 177 PKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFN P TYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDG TYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG2-Fc
S(86)P 178 PKTASTIESKTGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSX ₂ YRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSD GTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPGK Example of an aglycosylated variant of feline IgG2-Fc
T(87) _X2
X ₂ = any amino acid except T or S 179 GGPSVFLFPPNPKDTLMITRTPEVTCVVVDVSQENPDVKFNWYMDGVEVRTATTRPKEEQFX ₁ STYRVVSVLRIQHQDWLSGKEFKCKVNNQALPQPIERTITKTKGRSQEPQVYVLAPHPDESKKSKVSVTCLVKDFYPPEINIEWQSNGQPELETKYSTTQAQQDSDGSYFLYSKLS VDRNRWQQGTTFTCGVMHEALHNHYTQKNVSKNPGK Example of an aglycosylated variant of equine IgG1-Fc
N(62)X ₁
X ₁ = any amino acid except N 180 GGPSVFLFPPNPKDTLMITRTPEVTCVVVDVSQENPDVKFNWYMDGVEVRTATTRPKEEQFN P TYRVVSVLRIQHQDWLSGKEFKCKVNNQALPQPIERTITKTKGRSQEPQVYVLAPHPDESKKSKVSVTCLVKDFYPPEINIEWQSNGQPELETKYSTTQAQQDSDGSYFLYSKLS VDRNRWQQGTTFTCGVMHEALHNHYTQKNVSKNPGK Example of an aglycosylated variant of equine IgG1-Fc
S(63)P 181 GGPSVFLFPPNPKDTLMITRTPEVTCVVVDVSQENPDVKFNWYMDGVEVRTATTRPKEEQFNSX ₂ YRVVSVLRIQHQDWLSGKEFKCKVNNQALPQPIERTITKTKGRSQEPQVYVLAPHPDESKKSKVSVTCLVKDFYPPEINIEWQSNGQPELETKYSTTQAQQDSDGSYFLYSK LSVDRNRWQQGTTFTCGVMHEALHNHYTQKNVSKNPGK Example of an aglycosylated variant of equine IgG1-Fc
T(64) _X2
X ₂ = any amino acid except T or S 182 GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFX ₁ STYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQ QVESFTCAVMHEALHNHFTKTDISESLGK Example of an aglycosylated variant of equine IgG2-Fc
N(62)X ₁
X ₁ = any amino acid except N 183 GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFN P TYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQ QVESFTCAVMHEALHNHFTKTDISESLGK Example of an aglycosylated variant of equine IgG2-Fc
S(63)P 184 GGPSVFIFPPNPKDALMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNSX ₂ YRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRW QQVESFTCAVMHEALHNHFTKTDISESLGK Example of an aglycosylated variant of equine IgG2-Fc
T(64) _X2
X ₂ = any amino acid except T or S 185 GGPSVFIFPPKPKDVLMITRMPEVTCLVVDVSHDSSDVLFTWYVDGTEVKTAKTMPNEEQNX ₁ STYRVVSVLRIQHQDWLNGKKFKCKVNNQALPAPVERTISKATGQTRVPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDITVEWQSNEHPEPEGKYRTTEAQKDSDGSYFLYSKLTVEKDRW QQGTTFTCVVMHEALHNHVMQKNISKNPGK Example of an aglycosylated variant of equine IgG3-Fc
N(62)X ₁
X ₁ = any amino acid except N 186 GGPSVFIFPPKPKDVLMITRMPEVTCLVVDVSHDSSDVLFTWYVDGTEVKTAKTMPNEEQNN P TYRVVSVLRIQHQDWLNGKKFKCKVNNQALPAPVERTISKATGQTRVPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDITVEWQSNEHPEPEGKYRTTEAQKDSDGSYFLYSKLTVEKDRWQQ GTTFTCVVMHEALHNHVMQKNISKNPGK Example of an aglycosylated variant of equine IgG3-Fc
S(63)P 187 GGPSVFIFPPKPKDVLMITRMPEVTCLVVDVSHDSSDVLFTWYVDGTEVKTAKTMPNEEQNNSX ₂ YRVVSVLRIQHQDWLNGKKFKCKVNNQALPAPVERTISKATGQTRVPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDITVEWQSNEHPEPEGKYRTTEAQKDSDGSYFLYSKLTVEKDRWQ QGTTFTCVVMHEALHNHVMQKNISKNPGK Example of an aglycosylated variant of equine IgG3-Fc
T(64) _X2
X ₂ = any amino acid except T or S 188 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQFX ₁ STYRVVSVLPIQHKDWLSGKEFKCKVNNKALPAPVERTISAPTGQPREPQVYVLAPHRDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDSDGSYFLYSKLTVETNRWQQ GTTFTCAVMHEALHNHYTEKSVSKSPGK Example of an aglycosylated variant of equine IgG4-Fc
N(62)X ₁
X ₁ = any amino acid except N 189 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQFN P TYRVVSVLPIQHKDWLSGKEFKCKVNNKALPAPVERTISAPTGQPREPQVYVLAPHRDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDSDGSYFLYSKLTVETNRWQQ GTTFTCAVMHEALHNHYTEKSVSKSPGK Example of an aglycosylated variant of equine IgG4-Fc
S(63)P 190 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQFNSX ₂ YRVVSVLPIQHKDWLSGKEFKCKVNNKALPAPVERTISAPTGQPREPQVYVLAPHRDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDSDGSYFLYSKLTVETNRWQ QGTTFTCAVMHEALHNHYTEKSVSKSPGK Example of an aglycosylated variant of equine IgG4-Fc
T(64) _X2
X ₂ = any amino acid except T or S 191 GGPSVFIFPPKPKDVLMISRKPEVTCVVVDLGHDDPDVQFTWFVDGVETHTATTEPKEEQFX ₁ PTYRVVSVLPIQHQDWLSGKEFKCSVTSKALPAPVERTISKAKGQLRVPQVYVLAPHPDELAKNTVSVTCLVKDFYPPEIDVEWQSNEHPEPEGKYSTTPAQLNSDGSYFLYSKLSVETSRW KQGESFTCGVMHEAVENHYTQKNVSHSPGK Example of an aglycosylated variant of equine IgG5-Fc
N(62)X ₁
X ₁ = any amino acid except N 192 GGPSVFIFPPKPKDVLMISRKPEVTCVVVDLGHDDPDVQFTWFVDGVETHTATTEPKEEQFN P TYRVVSVLPIQHQDWLSGKEFKCSVTSKALPAPVERTISKAKGQLRVPQVYVLAPHPDELAKNTVSVTCLVKDFYPPEIDVEWQSNEHPEPEGKYSTTPAQLNSDGSYFLYSKLSVETSRW KQGESFTCGVMHEAVENHYTQKNVSHSPGK Example of an aglycosylated variant of equine IgG5-Fc
S(63)P 193 GGPSVFIFPPKPKDVLMISRKPEVTCVVVDLGHDDPDVQFTWFVDGVETHTATTEPKEEQFNSX ₂ YRVVSVLPIQHQDWLSGKEFKCSVTSKALPAPVERTISKAKGQLRVPQVYVLAPHPDELAKNTVSVTCLVKDFYPPEIDVEWQSNEHPEPEGKYSTTPAQLNSDGSYFLYSKLSVETSR WKQGESFTCGVMHEAVENHYTQKNVSHSPGK Example of an aglycosylated variant of equine IgG5-Fc
T(64) _X2
X ₂ = any amino acid except T or S 194 GRPSVFIFPPNPKDTLMISRTPEVTCVVVDVSQENPDVKFNWYVDGVEAHTATTKAKEKQDX ₁ STYRVVSVLPIQHQDWRRGKEFKCKVNNRALPAPVERTITKAKGELQDPQVYILAPHPDEVTKNTVSVTCLVKDFYPPDINVEWQSNEEPEPEVKYSTTPAQLDGDGSYFLYSKLTVETDRWEQ GESFTCVVMHEAIRHTYRQKSITNFPGK Example of an aglycosylated variant of equine IgG6-Fc
N(62)X ₁
X ₁ = any amino acid except N 195 GRPSVFIFPPNPKDTLMISRTPEVTCVVVDVSQENPDVKFNWYVDGVEAHTATTKAKEKQDN P TYRVVSVLPIQHQDWRRGKEFKCKVNNRALPAPVERTITKAKGELQDPQVYILAPHPDEVTKNTVSVTCLVKDFYPPDINVEWQSNEEPEPEVKYSTTPAQLDGDGSYFLYSKLTVETDRWEQGES FTCVVMHEAIRHTYRQKSITNFPGK Example of an aglycosylated variant of equine IgG6-Fc
S(63)P 196 GRPSVFIFPPNPKDTLMISRTPEVTCVVVDVSQENPDVKFNWYVDGVEAHTATTKAKEKQDNSX ₂ YRVVSVLPIQHQDWRRGKEFKCKVNNRALPAPVERTITKAKGELQDPQVYILAPHPDEVTKNTVSVTCLVKDFYPPDINVEWQSNEEPEPEVKYSTTPAQLDGDGSYFLYSKLTVETDRWEQG ESFTCVVMHEAIRHTYRQKSITNFPGK Example of an aglycosylated variant of equine IgG6-Fc
T(64) _X2
X ₂ = any amino acid except T or S 197 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQNX ₁ STYRVVSILAIQHKDWLSGKEFKCKVNNQALPAPVQKTISKPTGQPREPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDGDGSYFLYSKLTV ETNRWQQGTTFTCAVMHEALHNHYTEKSVSKSPGK Example of an aglycosylated variant of equine IgG7-Fc
N(62)X ₁
X ₁ = any amino acid except N 198 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQNN P TYRVVSILAIQHKDWLSGKEFKCKVNNQALPAPVQKTISKPTGQPREPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDGDGSYFLYSKLTVETNR WQQGTTFTCAVMHEALHNHYTEKSVSKSPGK Example of an aglycosylated variant of equine IgG7-Fc
S(63)P 199 VGPSVFIFPPKPKDVLMISRTPTVTCVVVDVGHDFPDVQFNWYVDGVETHTATTEPKQEQNNSX ₂ YRVVSILAIQHKDWLSGKEFKCKVNNQALPAPVQKTISKPTGQPREPQVYVLAPHPDELSKNKVSVTCLVKDFYPPDIDIEWKSNGQPEPETKYSTTPAQLDGDGSYFLYSKLTVET NRWQQGTTFTCAVMHEALHNHYTEKSVSKSPGK Example of an aglycosylated variant of equine IgG7-Fc
T(64) _X2
X ₂ = any amino acid except T or S

DESCRIPTION OF IMPLEMENTATION OPTIONS

[0015] Variants of IgG-Fc polypeptides in companion animals such as dogs, horses and cats are described. In some embodiments, variant IgG-Fc polypeptides have increased binding to protein A, decreased binding to C1q, decreased binding to CD16, increased stability, increased production in a recombinant system, increased formation of disulfide bonds at the hinge region, and/or increased ability to form heterodimeric polypeptides . In some embodiments, the antibodies, antibody fragments, or fusion proteins comprise a variant IgG-Fc polypeptide. Also provided are methods for producing or purifying variants of IgG-Fc polypeptides and methods for administering variants of IgG-Fc polypeptides to domestic animals.

[0016] Various embodiments are also provided relating to continuous polypeptides and heterodimeric polypeptides comprising one or more variants of GLP-1 polypeptide(s) having a longer serum half-life. In some embodiments of the present invention, the continuous polypeptides or heterodimeric polypeptides comprise a GLP1 polypeptide and a glucagon polypeptide as a dual agonist of the GLP1 receptor and the glucagon receptor. In some embodiments, such polypeptides may be used to treat, for example, diabetes, obesity, or related diseases in companion animals such as dogs, cats, and horses.

[0017] For the convenience of the reader, the following definitions of terms used in this description are provided.

[0018] Numerical terms used herein, such as K _D , are calculated based on scientific measurements and thus may have associated measurement uncertainty. In some cases, a numerical term may include numerical values that are rounded to the nearest significant digit.

[0019] As used herein, the singular number means “at least one” or “one or more” unless otherwise indicated. As used herein, the term “or” means “and/or” unless otherwise indicated. In the context of multiple claim dependency, the use of “or” when referring to other claims refers to such claims only as an alternative.

Examples of IgG-Fc polypeptide variants

[0020] New variants of IgG-Fc polypeptides have been proposed, for example, variants of IgG-Fco polypeptides for increased binding to protein A, for reduced binding to C1q, for reduced binding to CD16, for increased stability, for increased production in a recombinant system, for increased formation of disulfide bonds in the hinge region and/or for the formation of heterodimeric proteins.

[0021] "Amino acid sequence" means the sequence of amino acid residues in a peptide or protein. The terms "polypeptide" and "protein" are used interchangeably to refer to a polymer of amino acid residues, and are not limited by a minimum length. Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers and multimers of amino acid residues. Both full-length proteins and their fragments are included in the definition. The terms also include post-expression modifications of the polypeptide, such as glycosylation, acetylation, sialylation, phosphorylation, and the like. Moreover, as used herein, “polypeptide” refers to a protein that includes modifications, such as deletions, additions and substitutions (generally conservative in nature), in the native sequence, as long as the protein retains the desired activity. These modifications may be targeted, such as by site-directed mutagenesis, or may be random, such as due to mutations in the hosts that produce the proteins or errors in PCR amplification.

[0022] A "crystallizable fragment" or "Fc polypeptide" is a region of an antibody molecule that interacts with effector molecules and cells. It includes the C-terminal region of the heavy chains of immunoglobulins. As used herein, an Fc polypeptide includes Fc domain fragments having one or more of the biological activities of a full-length Fc polypeptide. In some embodiments, the biological activity of the Fc polypeptide is the ability to bind to FcRn. In some embodiments, the biological activity of the Fc polypeptide is the ability to bind to C1q. In some embodiments, the biological activity of the Fc polypeptide is the ability to bind to CD16. In some embodiments, the biological activity of an Fc polypeptide is the ability to bind protein A. An "effector function" of an Fc polypeptide is an action or activity performed in whole or in part by any antibody in response to a stimulus, and may include complement fixation and/or induction of ADCC (antibody-dependent cellular cytotoxicity).

[0023] “IgX-Fc” refers to an Fc polypeptide derived from a specific antibody isotype (eg, IgG, IgA, IgD, IgE, IgM, etc.), where “X” denotes the antibody isotype. Thus, "IgG-Fc" means that the Fc polypeptide is derived from the γ chain, "IgA-Fc" means that the Fc polypeptide is derived from the α chain, "IgD-Fc" means that the Fc polypeptide is derived from β chain, "IgE-Fc" means that the Fc polypeptide is derived from the ε chain, "IgM-Fc" means that the Fc polypeptide is derived from the μ chain, etc. In some embodiments, the IgG-Fc polypeptide contains hinge, CH2 and CH3 regions, but does not include CH1 or CL. In some embodiments, the IgG-Fc polypeptide contains CH2 and CH3, but does not include CH1, hinge, or CL regions. In some embodiments, the IgG Fc polypeptide contains CH1, hinge, CH2, CH3 regions with or without CL. "IgX-N Fc" or "IgGXN Fc" means that the Fc polypeptide is derived from a specific antibody isotype subclass (such as canine IgG subclasses: IgG-A, IgG-B, IgG-C, or IgG-D; feline IgG subclasses: IgG1a , IgG1b or IgG2; or equine IgG subclasses: IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 or IgG7, etc.), where "N" denotes the subclass.

[0024] “Hinge region” refers to any region of an Fc polypeptide or Fc polypeptide variant that is proline-rich and contains at least one cysteine residue located between CH1 and CH2 of the full-length heavy chain constant region.

[0025] In some embodiments, the hinge region is capable of forming disulfide bonds within the same hinge region, within the same Fc polypeptide, with the hinge region of a separate Fc polypeptide, or with a separate Fc polypeptide. In some embodiments, the hinge region comprises at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least at least nine or at least ten proline residues.

[0026] The term "companion animals" refers to animals suitable to be a companion to a person. In some embodiments, the companion animal is a canid (or dog), a feline (or feline), or an equine (or horse). In some embodiments, the companion animal is a small mammal such as a canine, a feline, a dog, a cat, a rabbit, a ferret, a guinea pig, a rodent, or the like. In some embodiments, the companion animal is a farm animal such as a horse, cow, pig, and the like.

[0027] In some embodiments, the IgX-Fc polypeptide or IgX-N Fc polypeptide is derived from a companion animal such as a dog, cat, or horse. In some embodiments, IgG-Fc polypeptides are isolated from canine immunoglobulin gamma heavy chains, such as IgG-A, IgG-B, IgG-C, or IgG-D. In some cases, IgG-Fc polypeptides are isolated from feline immunoglobulin gamma heavy chains such as IgG1a, IgG1b or IgG2. In other cases, IgG-Fc polypeptides are isolated from equine immunoglobulin gamma heavy chains such as IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 or IgG7.

[0028] The terms “IgX-Fc” and “IgX-Fc polypeptide” include wild-type IgX-Fc polypeptides and variant IgX-Fc polypeptides unless otherwise noted.

[0029] “Wild type” refers to an unmutated version of a polypeptide that occurs in nature, or a fragment thereof. A wild-type polypeptide can be produced recombinantly.

[0030] In some embodiments, a wild-type IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 16, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 100, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 117, SEQ ID NO: 118.

[0031] A "variant" is a polypeptide that differs from the reference polypeptide by one or more non-native amino acid substitutions, deletions and/or additions. In some embodiments, the variant retains at least one biological activity of the reference polypeptide. In some embodiments, the variant (e.g., canine IgG-A Fc variant, canine IgG-C Fc variant, canine IgG-D-Fc variant, equine IgG2-Fc variant, equine IgG5-Fc variant, or equine IgG6-Fc variant) has activity , which is essentially absent from the reference polypeptide. For example, in some embodiments, the canine IgG-A Fc variant, the canine IgG-C Fc variant, the canine IgG-D-Fc variant, the equine IgG2-Fc variant, the equine IgG5-Fc variant, or the equine IgG6-Fc variant binds to protein A.

[0032] As used herein, "percentage (%) amino acid sequence identity" and "homology" with respect to a nucleic acid molecule or polypeptide sequence are defined as the percentage of nucleotides or amino acid residues in a reference sequence that are identical to nucleotide or amino acid residues in a particular nucleic acid molecule or polypeptide sequence after sequence alignment and introduction of breaks if necessary to achieve the maximum percentage of sequence identity, and without considering conservative substitutions as part of the sequence identity. Alignment to determine percent sequence identity can be accomplished in a variety of ways known to those skilled in the art, for example, using publicly available computer programs such as the BLAST, BLAST-2, ALIGN, or MEGALINE™ (DNASTAR) programs. Those skilled in the art can determine appropriate parameters for performing the alignment, including any algorithms necessary to achieve maximum alignment over the entire length of the sequences being compared.

[0033] In some embodiments, the variant has at least about 50% sequence identity with a reference nucleic acid or polypeptide molecule after sequence alignment and introduction of breaks as necessary to achieve the maximum percentage of sequence identity, and without regard to any conservative substitutions such as parts of sequence identity. Such variants include, for example, polypeptides in which one or more amino acid residues are added, deleted at the N- or C-terminus of the polypeptide. In some embodiments, the variant has at least about 50% sequence identity, at least about 60% sequence identity, at least about 65% sequence identity, at least about 70% sequence identity, at least about 75% sequence identity, at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence identity to a reference nucleic acid or polypeptide sequence.

[0034] A "point mutation" is a mutation that involves a single amino acid residue. A mutation can be the loss of an amino acid, the replacement of one amino acid residue with another, or the introduction of an additional amino acid residue.

[0035] The term "amino acid substitution" refers to the replacement of one amino acid in a polypeptide with another amino acid. In some embodiments, the amino acid substitution is a conservative substitution. Non-limiting examples of conservative amino acid substitutions are presented in Table 2. Amino acid substitutions can be introduced into the molecule of interest and the products analyzed for the desired activity, for example, preservation/improvement of antigen binding, reduced immunogenicity or improved ADCC or CDC or improved pharmacokinetic parameters.

[0036] Table 2.

Original balance Examples of substitutions Ala (A) Val; Leu; Ile Arg(R) Lys; Gln; Asn Asn(N) Gln; His; Asp; Lys; Arg Asp (D) Glu; Asn Cys(C) Ser; Ala Gln(Q) Asn; Glu Glu(E) Asp; Gln Gly (G) Ala His(H) Asn; Gln; Lys; Arg Ile (I) Leu; Val; Met; Ala; Ph; norleucine Leu (L) Norleucine; Ile; Val; Met; Ala; Phe Lys (K) Arg; Gln; Asn Met(M) Leu; Ph; Ile Phe (F) Trp; Leu; Val; Ile; Ala; Tyr Pro (P) Ala Ser (S) Thr Thr (T) Val; Ser Trp(W) Tyr; Phe Tyr (Y) Trp; Ph; Thr; Ser Val(V) Ile; Leu; Met; Ph; Ala; norleucine

[0037] Amino acids can be grouped according to general side chain properties:

(1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile;

(2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;

(3) acidic: Asp, Glu;

(4) basic: His, Lys, Arg;

(5) residues that affect chain orientation: Gly, Pro;

(6) aromatic: Trp, Tyr, Phe.

[0038] Non-conservative substitutions are the replacement of a member of one of these classes with an amino acid from another class.

[0039] The term "IgG-Fc variant" as used herein refers to an IgG-Fc polypeptide that differs from the reference IgG-Fc polypeptide by one or more amino acid substitutions, deletions and/or additions and substantially retains at least one biological activity of the reference IgG-Fc polypeptide.

[0040] The term “amino acid derivative” as used herein refers to any amino acid, modified amino acid, and/or amino acid analogue that is not one of the 20 commonly known naturally occurring amino acids found in the human body. Examples of amino acid derivatives include naturally occurring amino acids not found in humans (eg, selenocysteine and pyrrolysine, which may occur in some microorganisms) and unnatural amino acids. Typical amino acid derivatives include, but are not limited to, amino acid derivatives commercially available from chemical manufacturers (for example, available at sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16274965 as of May 6, 2017, which is included in this description by reference). One or more amino acid derivatives can be introduced into a polypeptide at a specific location by a translation system that uses host cells, orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNA and the amino acid derivative. For a more detailed description, see, for example, US Pat. No. 9,624,485.

[0041] In some embodiments, the IgG-Fc polypeptide variant comprises an amino acid substitution with an amino acid derivative. In some embodiments, the amino acid derivative is an alanine derivative, a cysteine derivative, an aspartic acid derivative, a glutamic acid derivative, a phenylalanine derivative, a glycine derivative, a histidine derivative, an isoleucine derivative, a lysine derivative, a leucine derivative, a methionine derivative, an asparagine derivative, a proline derivative, a derivative glutamine, arginine derivative, serine derivative, threonine derivative, valine derivative, tryptophan derivative or tyrosine derivative.

[0042] In some embodiments, the variant IgG-Fc polypeptide includes a variant of a companion animal IgG-Fc polypeptide. In some embodiments, the variant IgG-Fc polypeptide comprises a variant canine IgG-Fc polypeptide, a variant equine IgG-Fc polypeptide, or a variant feline IgG-Fc polypeptide.

Examples of IgG-Fc polypeptide variants with altered protein A binding

[0043] In some embodiments, the variant IgG-Fc polypeptide has a modified binding affinity for Protein A. In some embodiments, the variant IgG-Fc polypeptide has increased binding affinity for Protein A. In some embodiments, the variant IgG-Fc polypeptide may be purified with using protein A column chromatography.

[0044] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 21, position 23, position 25, position 80, position 205, and/or position 207 in SEQ ID NO: 1. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 21, position 23, and/or position 24 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 21, position 23 , position 25, position 80 and/or position 207 in SEQ ID NO: 4.

[0045] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 15 and/or position 203 in SEQ ID NO: 64. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to 199 and/or position 200 in SEQ ID NO: 67. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 199, position 200, position 201 and/or 202 in SEQ ID NO: 68.

[0046] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 21, position 23, position 25, position 80, position 205, and/or position 207 in SEQ ID NO: 1. In some embodiments, the variant polypeptide The IgG-Fc contains an amino acid substitution at position 21, position 23, and/or position 24 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 21, position 23, position 25, position 80, and/or or position 207 in SEQ ID NO: 3.

[0047] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 15 and/or position 203 in SEQ ID NO: 64. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 199 and/or position 200 in SEQ ID NO: 67. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 199, position 200, position 201, and/or position 202 in SEQ ID NO: 68.

[0048] In some embodiments, a variant IgG-Fc polypeptide comprises threonine at a position corresponding to position 21 in SEQ ID NO: 1, a leucine at a position corresponding to position 23 in SEQ ID NO: 1, an alanine at a position corresponding to position 25 in SEQ ID NO: 1, a glycine at a position corresponding to position 80 in SEQ ID NO: 1, an alanine at a position corresponding to position 205 in SEQ ID NO: 1, and/or a histidine at a position corresponding to position 207 in SEQ ID NO: 1. In some embodiments, the IgG-Fc polypeptide variant comprises threonine at a position corresponding to position 21 in SEQ ID NO: 3, a leucine at a position corresponding to position 23 in SEQ ID NO: 3, and/or isoleucine at a position corresponding to position 24 in SEQ ID NO: 3. In some embodiments, a variant IgG-Fc polypeptide contains threonine at a position corresponding to position 21 in SEQ ID NO: 4, a leucine at a position corresponding to position 23 in SEQ ID NO: 4, an alanine at a position corresponding to 25 in SEQ ID NO: 4, glycine at a position corresponding to position 80 in SEQ ID NO: 3, and/or histidine at a position corresponding to position 207 in SEQ ID NO: 4.

[0049] In some embodiments, the variant IgG-Fc polypeptide contains threonine or valine at a position corresponding to position 15 in SEQ ID NO: 64, and/or tyrosine or valine at a position corresponding to position 203 in SEQ ID NO: 64. In some In embodiments, the variant IgG-Fc polypeptide comprises a leucine at a position corresponding to position 199 in SEQ ID NO: 67 and/or a histidine at a position corresponding to position 200 in SEQ ID NO: 67. In some embodiments, a variant IgG-Fc polypeptide contains an isoleucine at a position corresponding to position 199 in SEQ ID NO: 68, a histidine at a position corresponding to position 200 in SEQ ID NO: 68, an asparagine at a position corresponding to position 201 in SEQ ID NO: 68, and/or a histidine at a position corresponding to provision 202 in SEQ ID NO: 68.

[0050] In some embodiments, the variant IgG-Fc polypeptide contains threonine at position 21 in SEQ ID NO: 1, leucine at position 23 in SEQ ID NO: 1, alanine at position 25 in SEQ ID NO: 1, glycine at position 80 in SEQ ID NO: 1, an alanine at position 205 in SEQ ID NO: 1, and/or a histidine at position 207 in SEQ ID NO: 1. In some embodiments, the IgG-Fc polypeptide variant includes a threonine at position 21 in SEQ ID NO: 1. 3, leucine at position 23 in SEQ ID NO: 3 and/or isoleucine at position 24 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains threonine at position 21 in SEQ ID NO: 4, leucine at position 23 in SEQ ID NO: 4, alanine at position 25 in SEQ ID NO: 4, glycine at position 80 in SEQ ID NO: 4, and/or histidine at position 207 in SEQ ID NO: 4.

[0051] In some embodiments, the variant IgG-Fc polypeptide contains threonine or valine at position 15 in SEQ ID NO: 64 and/or tyrosine or valine at position 203 in SEQ ID NO: 64. In some embodiments, the variant IgG-Fc polypeptide The Fc contains a leucine at position 199 in SEQ ID NO: 67 and/or a histidine at position 200 in SEQ ID NO: 67. In some embodiments, a variant IgG-Fc polypeptide contains an isoleucine at position 199 in SEQ ID NO: 68, a histidine at 200 in SEQ ID NO: 68, asparagine at position 201 in SEQ ID NO: 68, and/or histidine at position 202 in SEQ ID NO: 68.

[0052] In some embodiments, a variant IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62 or SEQ ID NO: 84. In some embodiments, the IgG-Fc polypeptide variant comprises SEQ ID NO: 19, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, or SEQ ID NO: 76.

Examples of IgG-Fc polypeptide variants with modified CD16 binding

[0053] In some embodiments, the variant IgG-Fc polypeptide has a modified binding affinity for CD16. In some embodiments, the variant IgG-Fc polypeptide has reduced binding affinity for CD16. In some embodiments, the IgG-Fc variant may produce reduced antibody-dependent cellular cytotoxicity (ADCC).

[0054] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 5, position 38, position 39, position 97, and/or position 98 in SEQ ID NO: 2. In some embodiments, the variant IgG polypeptide -Fc contains an amino acid substitution at a position corresponding to position 5, position 38, position 39, position 97 and/or position 98 in SEQ ID NO: 3.

[0055] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 5, position 38, position 39, position 97, and/or position 98 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid replacement at position 5, position 38, position 39, position 97 and/or position 98 in SEQ ID NO: 3.

[0056] In some embodiments, a variant IgG-Fc polypeptide comprises proline at position 5, glycine at position 38, arginine at position 39, isoleucine at position 97, and/or glycine at position corresponding to position 98 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains proline at position corresponding to position 5, glycine at position corresponding to position 38, arginine at position corresponding to position 39, isoleucine at position corresponding to position 97, and/or glycine at a position corresponding to position 98 in SEQ ID NO: 3.

[0057] In some embodiments, the variant IgG-Fc polypeptide contains proline at position 5, glycine at position 38, arginine at position 39, isoleucine at position 97, and/or glycine at position 98 in SEQ ID NO: 2. In some embodiments, the IgG-Fc polypeptide variant contains proline at position 5, glycine at position 38, arginine at position 39, isoleucine at position 97, and/or glycine at position 98 in SEQ ID NO: 3.

[0058] In some embodiments, the variant IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144 , SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156 or SEQ ID NO: 157.

Examples of IgG-Fc polypeptide variants with modified binding to C1q

[0059] In some embodiments, the variant IgG-Fc polypeptide has a modified binding affinity for C1q. In some embodiments, the variant IgG-Fc polypeptide has reduced binding affinity for C1q. In some embodiments, a variant IgG-Fc polypeptide may have reduced complement fixation. In some embodiments, the IgG-Fc variant may have a reduced complement-mediated immune response.

[0060] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 93 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 93 in SEQ ID NO: : 3. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 87 in SEQ ID NO: 63. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 87 in SEQ ID NO: : 65. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 87 in SEQ ID NO: 66. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 198 in SEQ ID NO: : 80. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 198 in SEQ ID NO: 81.

[0061] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 93 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 93 in SEQ ID NO: 3. In some embodiments a variant IgG-Fc polypeptide comprises an amino acid substitution at position 87 in SEQ ID NO: 63. In some embodiments, a variant IgG-Fc polypeptide comprises an amino acid substitution at position 87 in SEQ ID NO: 65. In some embodiments, a variant IgG-Fc polypeptide contains an amino acid substitution at position 87 in SEQ ID NO: 66. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 198 in SEQ ID NO: 80. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 198 in SEQ ID NO: 81.

[0062] In some embodiments, the variant IgG-Fc polypeptide contains arginine at a position corresponding to position 93 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains arginine at a position corresponding to position 93 in SEQ ID NO: 3 In some embodiments, the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 87 in SEQ ID NO: 63. In some embodiments, the variant IgG-Fc polypeptide contains a serine substitution at a position corresponding to position 87 in SEQ ID NO: 65. In some embodiments, the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 87 of SEQ ID NO: 66. In some embodiments, the variant IgG-Fc polypeptide contains an alanine at a position corresponding to position 198 of SEQ ID NO: 80. B In some embodiments, the variant IgG-Fc polypeptide contains an alanine at a position corresponding to position 198 in SEQ ID NO: 81.

[0063] In some embodiments, the variant IgG-Fc polypeptide contains an arginine at position 93 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 93 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 93 in SEQ ID NO: 3. the variant IgG-Fc polypeptide contains a serine at position 87 in SEQ ID NO: 63. In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 87 in SEQ ID NO: 65. In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 87 in SEQ ID NO: 66. In some embodiments, the variant IgG-Fc polypeptide contains an alanine at position 198 in SEQ ID NO: 80. In some embodiments, the variant IgG-Fc polypeptide contains an alanine at position 198 in SEQ ID NO: 81 .

[0064] In some embodiments, the variant IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 78, SEQ ID NO: 79, or SEQ ID NO: 84. In some embodiments, the variant IgG-Fc polypeptide contains the amino acid sequence of SEQ ID NO: 70 , SEQ ID NO: 73, SEQ ID NO: 74, or SEQ ID NO: 77. In some embodiments, the variant IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 82 or SEQ ID NO: NO: 83.

Examples of IgG-Fc polypeptide variants with a modified interchain disulfide bond

[0065] In some embodiments, the variant feline IgG-Fc polypeptide has at least one additional interchain disulfide bond relative to the wild-type feline IgG-Fc polypeptide. In some embodiments, the feline IgG-Fc polypeptide variant has at least one additional interchain disulfide bond in the hinge region. In some embodiments, a variant feline IgG2-Fc polypeptide with at least one additional interchain disulfide bond has increased interchain stability compared to a wild-type feline IgG-Fc polypeptide. In some embodiments, the variant IgG polypeptide has at least one amino acid modification in the hinge region relative to the wild-type IgG-Fc polypeptide. In some embodiments, the wild-type IgG-Fc polypeptide is a wild-type feline or equine IgG-Fc polypeptide. In some embodiments, a variant IgG-Fc polypeptide comprises a hinge region or a hinge region portion from a different isotype IgG-Fc polypeptide. In some embodiments, the variant IgG-Fc polypeptide comprises a hinge region from a wild-type feline IgG-1a-Fc polypeptide, a wild-type feline IgG-1b-Fc polypeptide, or a wild-type equine IgG1-Fc polypeptide. In some embodiments, the variant IgG2-Fc polypeptide has increased production in recombinant systems and/or increased disulfide bond formation at the hinge region relative to the wild-type IgG-Fc polypeptide. In some embodiments, increased production in the recombinant system and/or increased formation of disulfide bonds at the hinge region can be determined by SDS-PAGE under reducing and/or non-reducing conditions.

[0066] In some embodiments, the variant IgG-Fc polypeptide contains a cysteine at a position corresponding to position 8, position 9, position 10, position 11, position 12, position 13, position 14, position 15, or position 16 in SEQ ID NO: 16 In some embodiments, the variant IgG-Fc polypeptide contains a cysteine at position 8, position 9, position 10, position 11, position 12, position 13, position 14, position 15, or position 16 in SEQ ID NO: 16. In some embodiments, the IgG-Fc polypeptide variant contains the sequence SEQ ID NO: 17.

[0067] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118. In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at a position corresponding to position 3 and/or at a position corresponding to position 20 in SEQ ID NO: 129.

[0068] In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118. B In some embodiments, the variant IgG-Fc polypeptide contains an amino acid substitution at position 3 and/or at a position corresponding to position 20 in SEQ ID NO: 129.

[0069] In some embodiments, the variant IgG-Fc polypeptide contains a proline at a position corresponding to position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118 In some embodiments, the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 3 and/or a proline at a position corresponding to position 20 in SEQ ID NO: 129.

[0070] In some embodiments, the variant IgG-Fc polypeptide contains a proline at position 16 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118. In some In embodiments, the variant IgG-Fc polypeptide contains a serine at position 3 and/or a proline at position 20 in SEQ ID NO: 129.

[0071] In some embodiments, a variant IgG-Fc polypeptide comprises the sequence SEQ ID NO: 19, SEQ ID NO: 125 or SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135.

Examples of IgG-Fc polypeptide variants for heterodimeric polypeptides

[0072] In some embodiments, the heterodimeric polypeptide provided by the present invention is a bispecific antibody. A bispecific antibody specifically binds to two different epitopes or target molecules. In some embodiments, bispecific antibodies bind to two different epitopes of the same target molecule. Bispecific antibodies can be full-length antibodies or antibody fragments.

[0073] In some embodiments, the heterodimeric polypeptide comprises a first variant of an IgG-Fc polypeptide containing a knob mutation and a second variant of an IgG-Fc polypeptide containing a trench mutation. Non-limiting examples of peak-to-groove mutations are described, for example, in Merchant, A. M. et al. An efficient route to human bispecific IgG. Nat Biotechnol, 16(7):677-81 (1998).

[0074] In some embodiments, the canine variant or feline variant IgG-Fc polypeptide includes an overhang mutation. In some embodiments, the variant IgG-Fc polypeptide includes tyrosine or tryptophan at a position corresponding to position 138 in SEQ ID NO: 1. In some embodiments, the variant IgG-Fc polypeptide includes tyrosine or tryptophan at a position corresponding to position 137 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide includes tyrosine or tryptophan at a position corresponding to position 137 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide includes tyrosine or tryptophan at a position corresponding to position 138 in SEQ ID NO: 4. In some embodiments, the variant IgG-Fc polypeptide contains tryptophan at a position corresponding to position 154 in S SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO : 118.

[0075] In some embodiments, the variant IgG-Fc polypeptide contains tyrosine or tryptophan at position 138 in SEQ ID NO: 1. In some embodiments, the variant IgG-Fc polypeptide contains tyrosine or tryptophan at position 137 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains tyrosine or tryptophan at position 137 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains tyrosine or tryptophan at position 138 in SEQ ID NO: 4. In some embodiments, the variant The IgG-Fc polypeptide contains tryptophan at position 154 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118.

[0076] In some embodiments, the overhang mutation variant IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 115, SEQ ID NO: 119, SEQ ID NO: 121 or SEQ ID NO: 123.

[0077] In some embodiments, the canine variant or feline variant IgG-Fc polypeptide contains a dimple mutation. In some embodiments, the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 138, an alanine at a position corresponding to position 140, and/or a threonine at a position corresponding to position 181 in SEQ ID NO: 1. In some embodiments, the variant The IgG-Fc polypeptide contains a serine at a position corresponding to position 137, an alanine at a position corresponding to position 139, and/or a threonine at a position corresponding to position 180 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 137, an alanine at a position corresponding to position 139, and/or a threonine at a position corresponding to position 180 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains a serine at a position corresponding to position 138 , an alanine at a position corresponding to position 140, and/or a threonine at a position corresponding to position 181, in SEQ ID NO: 4. In some embodiments, a variant IgG-Fc polypeptide contains a serine at a position corresponding to position 154, an alanine at a position corresponding to at position 156, and/or threonine at a position corresponding to position 197 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118.

[0078] In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 138, an alanine at position 140, and/or threonine at position 181 in SEQ ID NO: 1. In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 137 , an alanine at position 139, and/or a threonine at position 181 in SEQ ID NO: 2. In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 137, an alanine at position 139, and/or a threonine at position 181 in SEQ ID NO: 3. In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 138, an alanine at position 140, and/or threonine at position 181 in SEQ ID NO: 4. In some embodiments, the variant IgG-Fc polypeptide contains a serine at position 154, an alanine at position 156 and/or a threonine at position 197 in SEQ ID NO: 16, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 118.

[0079] In some embodiments, a dimple mutant variant of an IgG-Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114, SEQ ID NO: 116, SEQ ID NO: 120, in SEQ ID NO: 122 or SEQ ID NO: 124.

[0080] In some embodiments, the continuous polypeptide comprises a GLP1 polypeptide and a variant of a canine or feline IgG-Fc polypeptide containing a knob mutation. In some embodiments, the continuous polypeptide comprises a glucagon polypeptide and a variant canine or feline IgG-Fc polypeptide containing a knob mutation. In some embodiments, the contiguous polypeptide comprises a GLP1 polypeptide and a variant canine or feline IgG-Fc polypeptide containing a dimple mutation. In some embodiments, the continuous polypeptide comprises a glucagon polypeptide and a variant of a canine or feline IgG-Fc polypeptide containing a dimple mutation.

[0081] In some embodiments, the heterodimeric polypeptide comprises a first continuous polypeptide comprising a GLP1 polypeptide and a variant of a canine or feline IgG-Fc polypeptide containing a knob mutation, and a second continuous polypeptide comprising a glucagon polypeptide and a variant of a canine or feline IgG-Fc polypeptide Fc containing the "hole" mutation. In some embodiments, the heterodimeric polypeptide comprises a first continuous polypeptide comprising a glucagon polypeptide and a canine or feline IgG-Fc polypeptide variant containing a knob mutation, and a second continuous polypeptide comprising a GLP1 polypeptide and a canine or feline IgG-Fc polypeptide variant containing "hole" mutation.

Examples of GLP-1 polypeptides and glucagon polypeptides

[0082] “GLP1” or “GLP1 polypeptide” as used herein is a polypeptide comprising full-length glucagon-like peptide-1 or a fragment thereof that binds to the glucagon-like peptide 1 receptor (GLP1R).

[0083] For example, "GLP1" refers to the GLP1 polypeptide of any vertebrate animal, including mammals such as primates (eg, humans and cynomolgus monkeys), rodents (eg, mice and rats), and companion animals (eg, dogs, cats and horses) unless otherwise stated. In some embodiments, the GLP1 polypeptide is a wild-type GLP1 polypeptide, such as GLP1(7-37) (SEQ ID NO: N: 85). In some embodiments, the GLP1 polypeptide is a variant of a GLP1 polypeptide, such as GLP1(7-36) (SEQ ID NO: 98), GLP1(7-35) (SEQ ID NO: 99), GLP1-S8(7-35) (SEQ ID NO: 86) or GLP1-G8 (7-35) (SEQ ID NO: 87). In some embodiments, GLP1 comprises the amino acid sequence of SEQ ID NO: 20.

[0084] "GLP1R" as used herein is a polypeptide containing a full-length glucagon-like peptide-1 receptor or a fragment thereof that is capable of binding to wild-type GLP1.

[0085] For example, "GLP1R" refers to the GLP1R polypeptide of any vertebrate animal, including mammals such as primates (eg, humans and cynomolgus monkeys), rodents (eg, mice and rats), and companion animals (eg, dogs, cats and horses) unless otherwise stated. In some embodiments, GLP1R is a fragment of an extracellular domain that binds a wild-type GLP1 polypeptide. In some embodiments, feline GLP1R contains the amino acid sequence of SEQ ID NO: 49. In some embodiments, feline GLP1R contains the amino acid sequence of SEQ ID NO: 48.

[0086] An “extracellular domain” (“ECD”) is a region of a polypeptide that extends from the transmembrane domain into the extracellular space. The term “extracellular domain” as used herein may include a full-length extracellular domain or may include a truncated extracellular domain missing one or more amino acids that binds its ligand. The composition of the extracellular domain may depend on the algorithm used to determine which amino acids are embedded in the membrane. Different extracellular domains for a given protein can be predicted using different algorithms and expressed using different systems.

[0087] “Glucagon” or “glucagon polypeptide” as used herein is a polypeptide containing full-length glucagon or a fragment thereof that binds to the glucagon receptor.

[0088] For example, “glucagon” refers to the glucagon polypeptide of any vertebrate animal, including mammals such as primates (e.g., humans and cynomolgus monkeys), rodents (e.g., mice and rats), and companion animals (e.g., dogs, cats and horses) unless otherwise stated. In some embodiments, the glucagon polypeptide is a wild-type glucagon polypeptide, for example, SEQ ID NO: 21.

Examples of IgG-Fc polypeptide variants and fusion molecules

[0089] Polypeptides and other molecules may contain a variant IgG-Fc polypeptide. In some embodiments, the fusion molecule comprises a variant IgG-Fc polypeptide, such as the variants of the IgG-Fc polypeptides described herein. In some embodiments, the antibody or antibody fragment comprises an IgG-Fc polypeptide variant, such as the IgG-Fc polypeptide variants described herein.

[0090] A "fusion molecule" as used herein refers to a molecule containing one or more "fusion partners". In some embodiments, the fusion partners are covalently linked (“fused”). If the two fusion partners are both polypeptides, the fusion partner polypeptides may be part of a contiguous amino acid sequence (ie, a contiguous polypeptide). The first fusion partner polypeptide may be linked to the N-terminus or C-terminus of the second fusion partner. In some embodiments, the fusion partners are translated as a single polypeptide with a coding sequence that encodes both fusion partners. Fusion partners, in addition to the peptide bond, can be covalently linked by other means, such as, for example, a chemical bond. Many known methods for covalently linking polypeptides to other molecules (eg, fusion partners) can be used. In other embodiments, the fusion partners are connected through a “linker” that consists of at least one amino acid or chemical moiety. In some embodiments, the fusion partners are non-covalently linked to each other. In some such embodiments, they may be linked, for example, using linking pairs. Typical binding pairs include, but are not limited to, biotin and avidin or streptavidin, an antibody and its antigen, and the like.

[0091] In some embodiments, the fusion partners comprise an IgG-Fc polypeptide, and at least one GLP1 polypeptide. In some embodiments, the fusion partners comprise an IgG-Fc polypeptide, a GLP1 polypeptide, and a glucagon polypeptide. In some embodiments, the GLP1 polypeptide may be linked to the N-terminus or C-terminus of an IgG-Fc polypeptide. In some embodiments, the glucagon polypeptide may be linked to either the N-terminus or C-terminus of an IgG-Fc polypeptide.

[0092] The term “continuous polypeptide” is used herein to refer to a contiguous sequence of amino acids. A contiguous polypeptide is usually translated from one contiguous DNA sequence. This can be accomplished using genetic engineering techniques, for example by removing a stop codon from the DNA sequence of the first protein and then adding the DNA sequence of a second protein while maintaining the reading frame, so that the DNA sequences are expressed as a single protein. Typically this is achieved by cloning the cDNA into an expression vector in the same reading frame as the existing gene.

[0093] "Linker" refers to one or more amino acid residues that connect a first polypeptide to a second polypeptide.

[0094] In some embodiments, the linker is a flexible, unstructured linker. In some embodiments, the linker is a glycine-rich, serine-rich, or glycine and serine-rich linker. In some embodiments, the linker contains 100%, at least 95%, at least 90%, or at least 85% serine and/or glycine amino acid residues.

[0095] "Extension" in the context of the present invention refers to one or more amino acid residues that are associated with the polypeptide at its C-terminus or at its N-terminus.

[0096] In some embodiments, this extension is flexible. In some embodiments, the extension imparts flexibility to the polypeptide without interfering with the biological activity of the polypeptide. In some embodiments of the present invention, extension increases the solubility of the polypeptide. In some embodiments of the present invention, the extension includes one or more glycine residues. In some embodiments, the extension includes a glycine residue (SEQ ID NO: 88), two glycine residues (SEQ ID NO: 89), three glycine residues (SEQ ID NO: 90), four glycine residues (SEQ ID NO: 91) , five glycine residues (SEQ ID NO: 92), six glycine residues (SEQ ID NO: 93), seven glycine residues (SEQ ID NO: 94), eight glycine residues (SEQ ID NO: 95) or more glycine residues.

[0097] In some embodiments, the continuous polypeptide comprises an IgG-Fc polypeptide comprising the amino acid sequence of any of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , 14, 15, 16, 17, 18, 19, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 , 79, 80, 81, 82, 83, 84, 100, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124 , 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 1 50 , 151, 152, 153, 154, 155, 156, 167, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 1 75 and a GLP1 polypeptide comprising the amino acid sequence of SEQ ID NO: 85. In some embodiments, the contiguous polypeptide comprises an IgG-Fc polypeptide comprising the amino acid sequence of any of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 100, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145 , 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 167, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170 , 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195 , 196, 197, 198, or 199, and a GLP1 polypeptide comprising the amino acid sequence of SEQ ID NO: 86. In some embodiments, the continuous polypeptide comprises an IgG-Fc polypeptide comprising the amino acid sequence of any of SEQ ID NO: 1, 2, 3, 4 , 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 , 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 100, 107, 108, 109, 110, 111, 112, 113, 114, 115 , 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 1 41 , 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 167, 158, 159, 160, 161, 162, 163, 164, 165, 1 66 , 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 1 91 , 192, 193, 194, 195, 196, 197, 198, or 199, and a GLP1 polypeptide comprising the amino acid sequence of SEQ ID NO: 87. In some embodiments, the contiguous polypeptide comprises an IgG-Fc polypeptide comprising the amino acid sequence of any of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 100, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135 , 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 167, 158, 159, 160, 161 , 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186 , 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, or 199, and a GLP1 polypeptide comprising the amino acid sequence of SEQ ID NO: 98. In some embodiments, the continuous polypeptide comprises an IgG- Fc containing the amino acid sequence of any of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 60 , 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 100 , 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 1 31 , 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 1 67 , 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 1 82 , 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, or 199, and a GLP1 polypeptide containing the amino acid sequence of SEQ ID NO: 99.

[0098] In some embodiments, the continuous polypeptide comprises an IgG-Fc polypeptide comprising the amino acid sequence of any of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , 14, 15, 16, 17, 18, 19, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 , 79, 80, 81, 82, 83, 84, 100, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124 , 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 1 50 , 151, 152, 153, 154, 155, 156, 167, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 1 75 and glucagon polypeptide containing the amino acid sequence SEQ ID NO: 21.

[0099] In some embodiments, the contiguous polypeptide comprises a first GLP1 polypeptide (GLP1A), a first linker (L1), a companion animal Fc polypeptide, optionally a second linker (L2), and optionally a second GLP1 polypeptide (GLP1B). In some embodiments, the continuous polypeptide comprises:

formula (I): GLP1A-L1-Fc;

formula (II): Fc-L1-GLP1A; or

formula (III): GLP1A-L1-Fc-L2-GLP1B.

[00100] In some embodiments, the contiguous polypeptide comprises a GLP1 polypeptide, a first linker (L1), an Fc polypeptide, a second linker (L2), and a glucagon polypeptide (Gluc). In some embodiments, the continuous polypeptide comprises:

formula (IV): GLP1-L1-Fc-L2-Gluc; or

formula (V): Gluc-L1-Fc-L2-GLP1.

[00101] In some embodiments, the GLP1 fusion molecule has a longer serum half-life compared to the wild-type GLP1 polypeptide. The increased half-life of the GLP1 fusion molecules described herein may require lower dosages and less frequent administration than the wild-type GLP1 polypeptide dosing schedule.

[00102] In some embodiments, GLP1B, if present, contains the same amino acid sequence as GLP1A.

[00103] In some embodiments, GLP1, GLP1A, or GLP1B, if present, comprises a wild-type GLP1 polypeptide. In some embodiments, GLP1, GLP1A, or GLP1B, if present, comprise a GLP1 polypeptide variant. In some embodiments, GLP1, GLP1A, or GLP1B, if present, comprises the amino acid sequence of SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 98, or SEQ ID NO: 99.

[00104] In some embodiments, the glucagon polypeptide comprises a wild-type glucagon polypeptide. In some embodiments, the glucagon polypeptide comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments, the glucagon polypeptide comprises a variant glucagon polypeptide.

[00105] In some embodiments, the Fc polypeptide is a human IgG-Fc. In some embodiments, the Fc polypeptide is a human IgG1-Fc, a human IgG2-Fc, a human IgG3-Fc, or a human IgG4-Fc. In some embodiments, the Fc polypeptide is a human IgG-Fc variant.

[00106] In some embodiments, the Fc polypeptide is a companion animal IgG-Fc. In some embodiments, the Fc polypeptide is canine IgG-A-Fc, canine IgG-B-Fc, canine IgG-C-Fc, canine IgG-D-Fc. In some embodiments, the Fc is equine IgG1-Fc, equine IgG2-Fc, equine IgG3-Fc, equine IgG4-Fc, equine IgG5-Fc, equine IgG6-Fc, or equine IgG7-Fc. In some embodiments, the Fc is a feline IgG1a-Fc, a feline IgG1b-Fc, or a feline IgG2-Fc.

[00107] In some embodiments, the Fc polypeptide is an IgG-Fc variant. In some embodiments, the Fc polypeptide is a canine IgG-A-Fc variant, a canine IgG-B-Fc variant, a canine IgG-C-Fc variant, a canine IgG-D-Fc variant. In some embodiments, the Fc is an IgG1-Fc variant Equine Fc, equine IgG2-Fc variant, equine IgG3-Fc variant, equine IgG4-Fc variant, equine IgG5-Fc variant, equine IgG6-Fc variant, or equine IgG7-Fc variant. In some embodiments, the Fc is a feline IgG1a-Fc variant, a feline IgG1b-Fc variant, or a feline IgG2-Fc variant.

[00108] In some embodiments, L1 and L2, if present, are each independently a flexible linker. In some embodiments, the amino acid sequence of L1 and L2, if present, each independently contains 100%, at least 95%, at least 90%, at least 85% serine and/or glycine amino acid residues.

[00109] In some embodiments, the continuous polypeptide contains an extension at its C-terminus. In some embodiments, the contiguous polypeptide contains a glycine residue, two glycine residues, three glycine residues, four glycine residues, five glycine residues, six glycine residues, seven glycine residues, eight glycine residues, or more than eight glycine residues at its C-terminus. In some embodiments, the contiguous polypeptide comprises the amino acid sequence of SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94 or SEQ ID NO: 95 at its C-terminus.

[00110] In some embodiments, the contiguous polypeptide comprises the amino acid sequence of SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 27; SEQ ID NO: 28; SEQ ID NO: 29; SEQ ID NO: 30; SEQ ID NO: 31; SEQ ID NO: 32; SEQ ID NO: 33; SEQ ID NO: 34; SEQ ID NO: 35; SEQ ID NO: 36; SEQ ID NO: 37; SEQ ID NO: 38; SEQ ID NO: 39; SEQ ID NO: 40; SEQ ID NO: 41; SEQ ID NO: 42; SEQ ID NO: 43; SEQ ID NO: 44; SEQ ID NO: 45; SEQ ID NO: 46; SEQ ID NO: 47, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 52; SEQ ID NO: 53; SEQ ID NO: 54; SEQ ID NO: 55; SEQ ID NO: 56; SEQ ID NO: 57; SEQ ID NO: 58; SEQ ID NO: 59; SEQ ID NO: 103; SEQ ID NO: 104; SEQ ID NO: 105 or SEQ ID NO: 106.

[00111] A nucleotide sequence encoding a polypeptide of interest, such as an IgG-Fc polypeptide variant or other polypeptide described herein, can be inserted into an expression vector suitable for expression in a selected host cell. A variant IgG-Fc polypeptide or other polypeptide described herein can be expressed by culturing a host cell transfected with an expression vector containing the nucleotide sequence.

[00112] A "vector" is a plasmid that can be used to transfer a DNA sequence from one organism to another or to express a gene of interest. The vector typically includes an origin of replication and regulatory sequences that regulate expression of the gene of interest, and may or may not carry a selectable marker gene, such as an antibiotic resistance gene. The vector is suitable for the host cell in which it is to be expressed. A vector may be called a "recombinant vector" when the gene of interest is present in the vector.

[00113] The term “host cell” refers to a cell that can be or is the recipient of a vector or isolated polynucleotide. The host cells can be prokaryotic cells or eukaryotic cells. Examples of eukaryotic cells include mammalian cells, such as primate or other animal cells; fungal cells such as yeast; plant cells; and insect cells. Non-limiting examples of mammalian cells include, but are not limited to, NS0 cells, PER.C6® cells (Crucell), 293 cells and CHO cells, and derivatives thereof such as 293-6E, DG44, CHO-S and CHO-K cells. Host cells include the progeny of a single host cell, and the progeny need not be completely identical (in morphology or genomic DNA match) to the original parent cell due to natural, random, or targeted mutations. The host cell includes cells transfected in vivo with polynucleotide(s) encoding the amino acid sequence(s) provided herein.

[00114] The term “isolated” as used herein refers to a molecule that has been separated from at least some of the components with which it typically occurs in nature or is produced. For example, a polypeptide is referred to as “isolated” when it is separated from at least some of the components of the cell in which it was produced. If a polypeptide is secreted by a cell after expression, then the physical separation of the supernatant containing the polypeptide from the cells that produce the peptide is considered to be “secreting” the polypeptide. Likewise, a polynucleotide is referred to as “isolated” when it is not part of a larger polynucleotide (e.g., genomic DNA or mitochondrial DNA, in the case of a DNA polynucleotide) in which it normally occurs in nature, or is separated from at least some from components of the cell in which it was produced, for example in the case of an RNA polynucleotide. Thus, a DNA polynucleotide that is contained in a vector within a host cell may be referred to as “isolated.”

[00115] The term “signal sequence” refers to a sequence of amino acid residues or polynucleotide encoding it that facilitates secretion of the polypeptide of interest and is typically cleaved after export of the polypeptide from the outer surface of the cell membrane.

[00116] In some embodiments, a variant IgG-Fc polypeptide or a continuous polypeptide containing a variant Fc polypeptide is isolated using chromatography, such as size exclusion chromatography, ion exchange chromatography, Protein A column chromatography, hydrophobic interaction chromatography, and CHT chromatography.

[00117] A label may be attached to IgG-Fc variant polypeptides or a continuous polypeptide containing a variant Fc polypeptide. "Label" means a group attached to a molecule to enable its detection. In some embodiments, a variant IgG-Fc polypeptide or a continuous polypeptide containing a variant Fc polypeptide is labeled with a detectable moiety, including, but not limited to, radioisotopes, fluorescent tags, and various enzyme-substrate tags known in the art. In some embodiments, the label is a detectable marker that can produce a visually or instrumentally detectable signal, for example, by introducing a radiolabeled amino acid or by attaching biotin moieties to the polypeptide that can be detected by labeled avidin (e.g., streptavidin containing a fluorescent marker or enzymatic activity that can be detected using optical or colorimetric methods). Examples of labels for polypeptides include, but are not limited to, the following labels: radioisotopes or radionuclides (e.g., 3 ³ H, ¹⁴ C, ³⁵ S, ⁹⁰ Y, ⁹⁹ Tc, ¹¹¹ In, ¹²⁵ I, ¹³¹ I, ¹⁷⁷ Lu, ¹⁶⁶ Ho or ¹⁵³ Sm); chromogens, fluorescent tags (eg, FITC, rhodamine, lanthanide phosphors), enzymatic tags (eg, β-galactosidase, horseradish peroxidase, luciferase, alkaline phosphatase); chemiluminescent markers; biotinyl groups; specified polypeptide epitopes recognized by a secondary reporter (eg, paired leucine zipper sequences, secondary antibody binding sites, metal binding domains, epitope tags); and magnetic agents such as gadolinium chelates. Typical examples of labels commonly used for immunoassays include moieties that produce light, such as acridinium compounds, as well as moieties that produce fluorescence, such as fluorescein. Thus, the fragment itself may not be a detectable label, but may become detectable when reacted with another fragment. The general techniques to be used when performing the various immunoassays mentioned above are known to those skilled in the art.

Examples of the affinity of IgG-Fc polypeptide variants for protein A and/or C1q and/or CD16

[00118] Variants of the IgG-Fc polypeptides described herein may have altered binding affinities for protein A and/or C1q and/or CD16. In some embodiments, the variant IgG-Fc polypeptide has increased protein A binding affinity relative to the wild-type IgG-Fc polypeptide. Such variant IgG-Fc polypeptides can be purified by Protein A column chromatography. In some embodiments, the variant IgG-Fc polypeptide has a reduced binding affinity for C1q relative to the wild-type IgG-Fc polypeptide. Such variants of IgG-Fc polypeptides may have a reduced complement-mediated immune response. In some embodiments, the variant IgG-Fc polypeptide has reduced binding affinity for CD16 relative to the wild-type IgG-Fc polypeptide. Such IgG-Fc polypeptide variants may have a reduced ADCC immune response. In some embodiments, a variant IgG-Fc polypeptide has increased binding affinity for Protein A relative to a wild-type IgG-Fc polypeptide and/or reduced binding affinity for C1q relative to a wild-type IgG-Fc polypeptide, and/or reduced binding affinity for CD16 relative to an IgG polypeptide -Fc wild type.

[00119] "Protein A" as used herein is a polypeptide containing full-length Protein A or a portion thereof that is capable of binding wild-type canine IgG-B-Fc, wild-type equine IgG1-Fc, wild-type equine IgG3-Fc, wild-type type IgG4-Fc equine, wild type IgG7-Fc equine, wild type IgG1a-Fc feline, wild type IgG1b-Fc feline or wild type IgG2-Fc feline.

[00120] The terms “C1q” or “C1q complex” are used interchangeably to refer to a complement protein complex or portion thereof that can bind wild-type canine IgG-B-Fc, wild-type canine IgG-C-Fc, wild-type canine type equine IgG1-Fc, wild type equine IgG3-Fc, wild type equine IgG4-Fc, wild type equine IgG7-Fc, wild type feline IgG1a-Fc, or wild type feline IgG1b-Fc.

[00121] "CD16" as used herein is a polypeptide comprising full-length CD16 or a portion thereof that is capable of binding wild-type canine IgG-A-Fc or wild-type canine IgG-Fc-D. The term "binds to a substance" is a term that is well known in the art, and methods for determining such binding are also well known in the art. A molecule is said to exhibit "binding" if it reacts with, associates with, or has an affinity for a particular cell or substance, and the reaction, association, or affinity is detected by one or more methods known in the art, such as, for example, immunoblotting, ELISA, KinEx A, biolayer interferometry (BLI), surface plasmon resonance, etc.

[00122] The term “Protein A+” as used herein means that an Fc polypeptide has an affinity for protein A. In some embodiments, the “Protein A+” Fc polypeptide contains at least one amino acid modification that increases binding affinity to protein A.

[00123] The term "Protein A -" as used herein means that an Fc polypeptide has low or no affinity for Protein A.

[00124] The term “C1q+” as used herein means that the Fc polypeptide has an affinity for C1q.

[00125] The term "C1q -" as used herein means that the Fc polypeptide has little or no affinity for C1q. In some embodiments, the C1q-Fc polypeptide has at least one amino acid modification that reduces binding affinity for C1q.

[00126] The term “CD16+” as used herein means that the Fc polypeptide has an affinity for CD16.

[00127] The term "CD16 -" as used herein means that the Fc polypeptide has low or no affinity for CD16. In some embodiments, the "CD16 -" Fc polypeptide has at least one amino acid modification that reduces binding affinity for CD16.

[00128] The term "affinity" refers to the strength of the total sum of non-covalent interactions between one binding site of a molecule (eg, a receptor) and its binding partner (eg, a ligand). The affinity of a molecule X and its partner Y can generally be represented by the dissociation constant (K _D ). Affinity can be measured by conventional methods known in the art, such as, for example, immunoblotting, ELISA, KinEx A, biolayer interferometry (BLI) or surface plasmon resonance.

[00129] The term “surface plasmon resonance” refers to an optical phenomenon that allows the analysis of biospecific interactions in real time by detecting changes in protein concentrations in a biosensor matrix, for example, using the BIAcore™ system (BIAcore International AB, a GE Healthcare company, Uppsala, Sweden and Piscataway, N.J.). A more detailed description is given in Jonsson et al. (1993) Ann. Biol. Clin. 51: 19-26.

[00130] The term "biolayer interferometry" refers to an optical analytical technique that analyzes the interference pattern of light reflected from the immobilized protein layer at the tip of the biosensor and the internal reference layer. Changing the number of molecules associated with the biosensor tip causes shifts in the interference pattern that can be measured in real time. A non-limiting example of a device for biolayer interferometry is the Octet® system (Pall ForteBio LLC). See, for example, Abdiche et al., 2008, Anal. Biochem. 377: 209-277.

[00131] The terms " _KD ", " _Kd ", "Kd" or "Kd value" are used interchangeably to refer to the equilibrium dissociation constant of a ligand-receptor or antibody-antigen interaction.

[00132] In some embodiments, a variant IgG-Fc polypeptide binds to protein A with a dissociation constant (K _D ) below 5×10 ^-6 M, below 1×10 ^-6 M, below 5×10 ^-7 M, below 1 ×10 ^-7 M, below 5×10 ^-8 M, below 1×10 ^-8 M, below 5×10 ^-9 M, below 1×10 -9 M, below 5× ^{10 -10 M} , below 1×10 ^-10 M, below 5×10 ^-11 M, below 1×10 ^-11 M, below 5×10 ^-12 M or below 1×10 ^-12 M, which is measured by biolayer interferometry.

[00133] In some embodiments, a variant IgG-Fc polypeptide binds to C1q or CD16 with a dissociation constant (K _D ) greater than 5×10 ^-6 M, greater than 1×10 ^-5 M, greater than 5×10 ^-5 M, greater 1×10 ^-4 M, above 5×10 ^-4 M or above 1×10 ^-3 M, which is measured by biolayer interferometry.

[00134] In some embodiments, the K _D of binding of an IgG-Fc polypeptide, such as a variant IgG-Fc polypeptide, to protein A or C1q or CD16 is measured using a biolayer interferometry assay using a biosensor, such as the ^Octet® System (Pall ForteBio LLC, Fremont, CA), in accordance with the supplier's instructions. Briefly, biotinylated protein A or C1q or CD16 is associated with the sensor tip and the association of the IgG-Fc polypeptide is monitored for a certain time or until equilibrium is reached. Dissociation can be controlled over a period of time or until equilibrium is reached. The values of the background curve obtained using the buffer are subtracted to eliminate the influence of the background. Data were fit to a 2:1 binding model using ForteBio analytical software to determine the association rate constant (k _on ), dissociation rate constant (k _off ) and K _d . The equilibrium dissociation constant (K _D ) is calculated as the ratio k _off /k _on . The term "k _on " refers to the rate constant of association of molecule X and its partner Y, and the term "k _off " refers to the rate constant of dissociation of molecule X and its partner Y from the molecule of the X/Y partner complex.

[00135] “Increase” or “stimulation” means an increase, improvement, or enhancement of activity, function, or quantity relative to a reference. In some embodiments, by "increase" or "boost" is meant the ability to cause an overall increase of about 5% or more, about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 100% or more, about 125% or more, approximately 200% or more compared to the reference value. In some embodiments, by “increase” or “boost” is meant the ability to cause an overall increase of about 5-50%, about 10-20%, about 50-100%, about 25-70%, relative to a reference value. . In some embodiments, by “increase” or “stimulation” is meant the ability to cause an overall increase of 50% or more. In some embodiments, by “increase” or “boost” is meant the ability to cause an overall increase of 75%, 85%, 90%, 95% or more. In some embodiments, the amount specified above is stimulated or increased over a period of time compared to a control dose (eg, placebo) over the same period of time.

[00136] In some embodiments, the variant IgG-Fc polypeptide is capable of binding to protein A with an affinity increased by about 5% or more, about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 100% or more, about 125 % or more, about 150% or more, about 200% or more relative to the reference IgG-Fc polypeptide. In some embodiments, the variant IgG-Fc polypeptide is capable of binding to protein A with an affinity increased by about 5-50%, about 10-20%, about 50-100%, about 25-70% compared to the control IgG polypeptide -Fc. In some embodiments, the reference IgG-Fc polypeptide is a wild-type IgG-Fc polypeptide. In some embodiments, the reference IgG-Fc polypeptide is another variant of the IgG-Fc polypeptide.

[00137] “Decrease” or “inhibition” means a decrease, decrease or stop of activity, function or amount compared to a reference. In some embodiments, by “reducing” or “inhibiting” is meant the ability to cause an overall reduction of about 5% or more, about 10% or more, about 20% or more, about 30% or more, about 40% or more. more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 90% or more compared to the reference IgG-Fc polypeptide. In some embodiments, by “reduction” or “inhibition” is meant the ability to cause an overall reduction of about 5-50%, about 10-20%, about 50-100%, about 25-70% compared to a reference value . In some embodiments, “reduction” or “inhibition” refers to the ability to cause an overall reduction of 50% or more. In some embodiments, “reduction” or “inhibition” refers to the ability to cause an overall reduction of 75%, 85%, 90%, 95%, or greater. In some embodiments, the amount specified above is inhibited or reduced over a period of time compared to a control dose (eg, placebo) over the same period of time.

[00138] In some embodiments, a variant IgG-Fc polypeptide is capable of binding to C1q or CD16 with an affinity reduced by about 5% or more, about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more relative to the reference IgG-Fc polypeptide. In some embodiments, the variant IgG-Fc polypeptide is capable of binding to C1q or CD16 with an affinity reduced by about 5-50%, about 10-20%, about 50-100%, about 25-70% compared to the reference IgG-Fc polypeptide. In some embodiments, the reference IgG-Fc polypeptide is a wild-type IgG-Fc polypeptide. In some embodiments, the reference IgG-Fc polypeptide is another variant of the IgG-Fc polypeptide.

[00139] The term "reference (reference)" as used herein refers to any sample, standard, or level that is used for comparison purposes. The reference may be a wild-type reference or a variant reference. The reference may be derived from a sample from a healthy or a non-diseased individual. In some examples, the standard is obtained from a sample from a healthy or non-diseased companion animal. In some examples, the standard is obtained from one or more healthy animals of a particular species that are not being tested or treated.

Examples of biological activity of GLP1 fusion variants

[00140] In some embodiments, the GLP1 fusion molecule binds to GLP1R and activates cAMP production. In some embodiments, the GLP1 fusion polypeptide increases cAMP production in the cell by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% compared to the signal in the absence of the GLP1 fusion polypeptide.

Examples of Pharmaceutical Compositions

[00141] The terms "pharmaceutical preparation" and "pharmaceutical composition" refer to a preparation that is in such a form as to provide the biological activity of the active ingredient(s), and which does not contain any additional components that are unacceptably toxic to the subject to whom the composition will be administered.

[00142] The term "pharmaceutically acceptable carrier" refers to a non-toxic solid, semi-solid or liquid excipient, diluent, encapsulating material, excipient or carrier commonly used in the art for use with a therapeutic agent, which together form a "pharmaceutical composition" for administration subject. The pharmaceutically acceptable carrier is non-toxic to recipients at the dosages and concentrations used and is compatible with the other ingredients of the composition. A pharmaceutically acceptable carrier is suitable for the composition used. Examples of pharmaceutically acceptable carriers include alumina; aluminum stearate; lecithin; serum proteins such as human serum albumin, canine or other animal serum albumin; buffers such as phosphate, citrate, tromethamine or HEPES buffers; glycine; sorbic acid; potassium sorbate; mixtures of partial glycerides of saturated vegetable fatty acids; water; salts or electrolytes such as protamine sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silicon dioxide, or magnesium trisilicate; polyvinylpyrrolidone, cellulose-based substances; polyethylene glycol; sucrose; mannitol; or amino acids, including, but not limited to, arginine.

[00143] The pharmaceutical composition may be stored in lyophilized form. Thus, in some embodiments of the invention, the production method includes a lyophilization step. The lyophilized composition can then be converted into another form, typically an aqueous composition suitable for parenteral administration, before administration to the dog, cat or horse. In other embodiments of the invention, particularly if the IgG-Fc polypeptide variant or other polypeptide described herein is highly stable to thermal and oxidative denaturation, the pharmaceutical composition may be presented in the form of a liquid, that is, in the form of an aqueous composition, which can be administered to a dog, cat or horse directly or with appropriate dilution. The lyophilized composition can be reconstituted with sterile water for injection (WFI). Bacteriostatic reagents such as benzyl alcohol may be included. Thus, the invention relates to pharmaceutical compositions in solid or liquid form.

[00144] Upon administration, the pH of the pharmaceutical compositions may range from about pH 5 to about pH 8. The compositions of the present invention are sterile if they are to be used for therapeutic purposes. Sterility can be achieved by any of several methods known in the art, including filtration through sterile filtration membranes (eg, 0.2 μm pore size membranes). Sterility can be maintained in the presence and absence of antibacterial agents.

Some uses of Fc polypeptides and pharmaceutical compositions

[00145] A polypeptide containing a variant Fc polypeptide, such as an IgG-Fc variant polypeptide of the invention, or pharmaceutical compositions containing a variant Fc polypeptide of the present invention may be useful for increasing the in vivo life of the product in a companion animal, including , but not limited to, canine, feline or equine.

[00146] As used herein, the term “treatment” is an approach to obtain useful or desired clinical results. The term "treatment" as used herein includes any administration or use of a therapeutic agent against a disease in a mammal, including a companion animal. For the purposes of this description, beneficial or desired clinical results include, but are not limited to, any one or more of the following: alleviation of one or more symptoms, reduction of disease severity, prevention or delay of disease spread, prevention or delay of disease recurrence, delay or delay of disease progression disease, improvement of the patient's condition, inhibition of the disease or development of the disease, inhibition or slowing of the disease or its development, cessation of the development of the disease and remission (partial or complete). Also, the term “treatment” includes the reduction of the pathological consequences of a proliferative disease. The methods provided herein provide for any one or more of these aspects of treatment. In connection with the above, the term treatment does not require one hundred percent elimination of all aspects of the disease.

[00147] The "therapeutically effective amount" of a substance/molecule, agonist, or antagonist may vary depending on factors such as the type of disease being treated, the disease state, the severity and course of the disease, the type of therapeutic targets, any prior therapy, clinical history, response to previous treatment, the judgment of the treating veterinarian, the age, sex and weight of the animal, and the ability of the substance/molecule, agonist or antagonist, to produce the desired response in the animal. A therapeutically effective amount is also one in which any toxic or harmful effects of the substance/molecule, agonist or antagonist are outweighed by the therapeutically beneficial effects. A therapeutically effective amount may be administered in one or more administrations. A therapeutically effective amount refers to an amount effective in dosages and for periods of time necessary to achieve the desired therapeutic or prophylactic result.

[00148] In some embodiments, a variant IgG-Fc polypeptide or other polypeptide described herein, or a pharmaceutical composition containing same, is administered parenterally, by subcutaneous administration, intravenous infusion, or intramuscular injection. In some embodiments, a variant IgG-Fc polypeptide or other polypeptide described herein, or a pharmaceutical composition containing same, is administered as a bolus injection or by continuous infusion over a period of time. In some embodiments, a variant IgG-Fc polypeptide or other polypeptide described herein, or a pharmaceutical composition containing them, is administered by the intramuscular route, intraperitoneal route, intracerebrospinal route, subcutaneous route, intra-arterial route, intra-articular route, intrathecal route, or inhalation way.

[00149] In some embodiments, a GLP1 fusion polypeptide or pharmaceutical compositions containing it can be used in accordance with the methods of the present invention for the treatment of diseases associated with high blood glucose levels. In some embodiments, the GLP1 fusion polypeptide or pharmaceutical compositions are administered to a companion animal, such as a canine, feline, or equine, to treat a disease associated with high blood glucose.

[00150] In some embodiments, a variant IgG-Fc polypeptide or other polypeptide described herein, or a pharmaceutical composition containing same, is administered in an amount ranging from 0.0001 mg/kg body weight to 100 mg/kg body weight per dose . In some embodiments, the GLP1 analogue may be administered in an amount ranging from 0.005 mg/kg body weight to 20 mg/kg body weight per dose. In some embodiments, the GLP1 analogue may be administered in an amount ranging from 1 mg/kg body weight to 10 mg/kg body weight per dose. In some embodiments, the GLP1 analogue may be administered in an amount ranging from 0.5 mg/kg body weight to 100 mg/kg body weight, ranging from 1 mg/kg body weight to 100 mg/kg body weight, ranging from 5 mg/kg body weight to 100 mg/kg body weight, in the range from 10 mg/kg body weight to 100 mg/kg body weight, in the range from 20 mg/kg body weight to 100 mg/kg body weight, in range from 50 mg/kg body weight to 100 mg/kg body weight, in the range from 1 mg/kg body weight to 10 mg/kg body weight, in the range from 5 mg/kg body weight to 10 mg/kg body weight, in the range from 0.5 mg/kg body weight to 10 mg/kg body weight or in the range from 5 mg/kg body weight to 50 mg/kg body weight.

[00151] In some embodiments, a variant IgG-Fc polypeptide or other polypeptide described herein, or a pharmaceutical composition containing same, is administered to a companion animal in a single or serial manner. In some embodiments, doses are administered once per week for at least two or three weeks, and in some embodiments, this treatment cycle is repeated two or more times, optionally one or more weeks apart without treatment. In other embodiments, the therapeutically effective dose is administered once daily for 2-5 days, and in some embodiments, this treatment cycle is repeated two or more times, optionally spaced one or more days or weeks apart without treatment.

[00152] Administration “in combination with” one or more additional therapeutic agents includes simultaneous (parallel) and sequential or alternate administration in any order. The term “simultaneous” is used herein to mean the administration of two or more therapeutic agents when the administrations at least partially overlap in time, or when the administration of one therapeutic agent occurs within a short period of time relative to the administration of another therapeutic agent. For example, two or more therapeutic agents are administered at a time interval not exceeding approximately a predetermined number of minutes. The term “sequentially” is used herein to mean the administration of two or more therapeutic agents, where the administration of one or more agents continues after the administration of one or more other agents has ceased, or where the administration of one or more other agents begins before the administration of one or more other agents. For example, the administration of two or more therapeutic agents occurs at a time interval greater than approximately a predetermined number of minutes. As used herein, the term “in combination with” refers to the use of one treatment modality in addition to another treatment modality. Thus, "in combination with" refers to the use of one treatment method before, during, or after the use of another treatment method on the animal.

[00153] In some embodiments, the dosage is administered once per week for at least two or three weeks, and in some embodiments, this treatment cycle is repeated two or more times, optionally one or more weeks apart without treatment. In other embodiments, the therapeutically effective dose is administered once daily for 2-5 days, and in some embodiments, this treatment cycle is repeated two or more times, optionally spaced one or more days or weeks apart without treatment.

[00154] Administration “in combination with” one or more additional therapeutic agents includes simultaneous (parallel) and sequential or alternate administration in any order. The term “simultaneous” is used herein to mean the administration of two or more therapeutic agents when the administrations at least partially overlap in time, or when the administration of one therapeutic agent occurs within a short period of time relative to the administration of another therapeutic agent. For example, two or more therapeutic agents are administered at a time interval not exceeding approximately a predetermined number of minutes. The term “sequentially” is used herein to mean the administration of two or more therapeutic agents, where the administration of one or more agents continues after the administration of one or more other agents has ceased, or where the administration of one or more other agents begins before the administration of one or more other agents. For example, the administration of two or more therapeutic agents occurs at a time interval greater than approximately a predetermined number of minutes. As used herein, the term “in combination with” refers to the use of one treatment modality in addition to another treatment modality. Thus, "in combination with" refers to the use of one treatment method before, during, or after the use of another treatment method on the animal.

[00155] In some embodiments, the method includes administering, in combination with a GLP1 fusion polypeptide, an insulin, a DPP4 inhibitor, an SGLT2 inhibitor, an A biguanide, a sulfonylurea, a meglitinide derivative, an alpha-glucosidase inhibitor, a thiazolidinedione (TZD), an amylinomimetic, a bile acid sequestrant, a dopamine agonist .

[00156] The following examples illustrate certain aspects of the invention and are not intended to limit the invention in any way.

EXAMPLES

Example 1

Canine IgG-Fc polypeptide variant with increased protein A binding and/or decreased complement binding and/or decreased CD16 binding

[00157] Antibody purification using protein A affinity is a well-established process. However, among the four canine IgG subtypes, only IgG-B-Fc (e.g., SEQ ID NO: 2 or SEQ ID NO: 107) has affinity for protein A. IgG-A Fc (e.g., SEQ ID NO: 1), IgG- C Fc (e.g., SEQ ID NO: 3 or SEQ ID NO: 108) and IgG-D-Fc (e.g., SEQ ID NO: 4) have weak or undetectable binding to Protein A. To produce polypeptides with altered binding to Protein A Canine polypeptide variants IgG-A-Fc, IgG-C-Fc and IgG-D-Fc were developed.

[00158] Additionally, canine IgG-B-Fc and IgG-C-Fc activate complement and bind to C1q, while canine IgG-A-Fc and IgG-D-Fc have weak or undetectable binding to C1q. To potentially reduce binding to C1q and/or potentially reduce the complement-mediated immune response, canine IgG-B-Fc and IgG-C-Fc polypeptide variants have been developed.

[00159] In addition, canine IgG-B-Fc and IgG-C-Fc are capable of binding to CD16. To potentially reduce IgG-B-Fc and IgG-C-Fc binding to CD16 and/or potentially reduce ADCC, canine IgG-B-Fc and IgG-C-Fc polypeptide variants have been developed.

[00160] Table 3 below shows the protein A and C1q binding characteristics for canine IgG-Fc subtypes. Notably, none of the wild-type canine IgG-Fc subtypes both lack C1q binding and have protein A binding.

[00161] Table 3.

Canine IgG Fc wild type Protein A binding Binding to C1q Binding to CD16 IgG-A-Fc - - - IgG-B-Fc + + + IgG-C-Fc - + + IgG-D-Fc - - -

(-) indicates low or undetectable binding activity.

[00162] Using 3D protein modeling and protein sequence analysis, canine IgG-B-Fc sequences that are likely to contact protein A were identified. Figure 1 shows a sequence alignment of the Fc regions of canine IgG-A, B, C, and D. The box indicates areas likely to contact protein A.

[00163] Two approaches have been used to create variants of canine IgG-A-, IgG-C- and IgG-D-Fc polypeptides with increased protein A binding. In the first approach, variants of canine IgG-A-, IgG-C-, and IgG-D-Fc polypeptides were generated that had the same protein A binding motif sequence from canine IgG-B-Fc (e.g., SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7, respectively). In the second approach, a canine IgG-A-Fc variant I(21)T/Q(207)H (SEQ ID NO: 60), a canine IgG-C-Fc variant I(21)T (SEQ ID NO: 61) were created and a canine IgG-D-Fc variant I(21)T/Q(207)H (SEQ ID NO: 62) having one or two amino acid substitutions in the protein A binding region to match the canine IgG-B-Fc sequence.

[00164] In addition, increased protein A binding variants of canine IgG-A-Fc, IgG-C-Fc, and IgG-D-Fc polypeptides can be produced that have one or more of the amino acid substitutions listed in Table 4.

[00165] Table 4.

Variants of amino acid substitutions* in canine IgG-Fc (Protein A +) Canine IgG-A-Fc
(SEQ ID NO: 1) Canine IgG-C-Fc
(SEQ ID NO: 3) Canine IgG-D-Fc
(SEQ ID NO: 4) Ile (21) Thr Ile (21) Thr Ile (23) Thr Arg (23) Leu Val (23) Leu Arg (23) Leu Thr (25) Ala Thr (24) Ile Thr (25) Ala Glu(80)Gly Glu(80)Gly Thr (205) Ala Gln(207)His Gln(207)His

*Amino acid positions are relative to SEQ ID NO.

[00166] In order to potentially reduce the binding of C1q to canine IgG-B-Fc and IgG-C-Fc and/or potentially reduce the complement-mediated immune response, variants of canine IgG-B-Fc and IgG-C-Fc polypeptides can be produced Fc having a Lys substitution with any amino acid other than Lys at a position corresponding to position 93 in SEQ ID NO: 2 or SEQ ID NO: 3, respectively. These amino acid substitutions were identified after protein sequence analysis and 3D structural modeling of canine IgG-B-Fc and IgG-C-Fc compared to canine IgG-A-Fc and IgG-D-Fc, which do not activate complement. For example, a canine IgG-B-Fc K(93)R variant (SEQ ID NO: 78) and a canine IgG-C-Fc K(93)R variant (SEQ ID NO: 79) can be produced. Decreased binding was observed between human C1q and the fusion protein containing the canine I IgG-B-Fc variant K(93)R compared to the fusion protein containing wild-type canine IgG-Fc-B.

[00167] In order to potentially reduce CD16 binding to IgG-B-Fc and IgG-C-Fc and/or potentially reduce ADCC, variants of canine IgG-B-Fc and IgG-C-Fc polypeptides having one or more of the amino acid substitutions listed in Table 5. The amino acid substitutions were identified after protein sequence analysis and 3D structural modeling of canine IgG-B and IgG-C compared to IgG-A and IgG-D, which are not known to activate ADCC .

[00168] Table 5.

Initial amino acid position* Substitutions Canine IgG-B-Fc
(SEQ ID NO: 2) Canine IgG-C-Fc
(SEQ ID NO: 3) Met (5) Leu (5) Any amino acid other than the parent residue such as Pro Asp (38) Asp (38) Any amino acid other than the parent residue such as Gly Pro (39) Pro (39) Any amino acid other than the parent residue such as Arg Lys (97) Lys (97) Any amino acid other than the parent residue such as Ile Ala (98) Ala (98) Any amino acid other than the parent residue such as Gly

*Amino acid positions are relative to SEQ ID NO.

[00169] Since the wild type canine IgG-C-Fc lacks protein A binding and has binding to C1q, a dual variant canine IgG-C-Fc that binds to protein A and has reduced binding to C1q can be produced by combining one or more of the amino acid substitutions listed in Table 4 with a K(93)R or K(93)X substitution, where X is any amino acid other than Lys. Dual canine IgG-B-Fc or IgG-C-Fc variants with reduced binding to C1q and reduced binding to CD16 can be prepared by combining one or more of the amino acid substitutions listed in Table 5 with a K(93)R substitution or K(93)X, where X represents any amino acid other than Lys. A canine IgG-C-Fc triple variant that binds protein A and has reduced binding to C1q and CD16 can be prepared by combining one or more of the amino acid substitutions listed in Table 4 and one or more of the amino acid substitutions listed in Table 5. with a K(93)R or K(93)X substitution, where X represents any amino acid other than Lys.

[00170] The binding of any variant canine IgG-Fc to protein A, CD16 and/or C1q can be determined and compared with the binding of another IgG-Fc to protein A, CD16 and/or C1q (e.g., the wild type of the corresponding canine IgG-Fc). Fc, with wild type or variant of another canine IgG-Fc or wild type or variant of another companion animal IgG-Fc, etc.).

[00171] Binding analysis can be performed using an Octet biosensor. Briefly, the target molecule (eg, protein A, C1q, CD16, etc.) is biotinylated, and free unreacted biotin is removed (eg, by dialysis). The biotinylated target molecule is captured by streptavidin at the sensor tip. The association of the target molecule with various concentrations (eg, 10 μg/ml) of IgG-Fc polypeptide is recorded over time or until steady state is reached. Dissociation can be controlled over time or until equilibrium is reached. The background curve values obtained using the buffer are subtracted to eliminate background influence. Data are fit to a 1:1 binding model using ForteBio™ analytical software to determine k _on , k _off and K _d .

Example 2

Equine IgG-Fc polypeptide variants to increase protein A binding and/or reduce complement fixation

[00172] Of the seven subtypes of equine IgG, IgG1-Fc (e.g., SEQ ID NO: 63), IgG3-Fc (e.g., SEQ ID NO: 65), IgG4-Fc (e.g., SEQ ID NO: 66) bind to protein A ), IgG7-Fc (eg, SEQ ID NO: 69). Equine IgG2-Fc (e.g., SEQ ID NO: 18, SEQ ID NO: 64), IgG5-Fc (e.g., SEQ ID NO: 67), and IgG6-Fc (e.g., SEQ ID NO: 68) have weak or undetectable binding with protein A. Variants of equine polypeptides IgG2-Fc, IgG5-Fc and IgG-Fc were created that have altered binding to protein A.

[00173] In addition, equine IgG2-Fc, IgG5-Fc and IgG6-Fc have weak or undetectable binding to C1q, while equine IgG1-Fc, IgG-Fc3, IgG4-Fc and IgG7-Fc bind to C1q. To potentially reduce binding to C1q and/or potentially reduce the complement-mediated immune response, variants of the equine polypeptides IgG1-Fc, IgG3-Fc, IgG4-Fc and IgG7-Fc were developed.

[00174] Table 6 shows the protein A and C1q binding characteristics of the equine IgG-Fc subtypes. Notably, none of the wild-type equine IgG-Fc subtypes have both a lack of C1q binding and protein A binding.

[00175] Table 6.

Wild-type equine IgG-Fc Protein A binding Binding to C1q IgG1-Fc + + IgG2-Fc - - IgG3-Fc + + IgG4-Fc + + IgG5-Fc - - IgG6-Fc - - IgG7-Fc + +

(-) indicates low or undetectable binding activity.

[00176] Using 3D protein modeling and protein sequence analysis, equine IgG1-Fc, IgG3-Fc, IgG4-Fc, and IgG7-Fc sequences that are likely to contact protein A have been identified. Equine IgG2-Fc polypeptide variants can be generated , IgG5-Fc, and IgG6-Fc having one or more amino acid substitutions listed in Table 7.

[00177] Table 7.

Variants of amino acid substitutions* in horse IgG-Fc (Protein A +) Equine IgG2-Fc
(SEQ ID NO: 64) Equine IgG5-Fc
(SEQ ID NO: 67) Equine Ig6-Fc
(SEQ ID NO: 68) Ala (15) Thr Val (199) Leu Ile (199) Leu Phe (203) Tyr Glu (200) Tyr Arg(200)His His (201) Asn Thr(202)His

*Amino acid positions are relative to SEQ ID NO.

[00178] For example, variants of the equine IgG2-Fc, IgG5-Fc, and IgG6-Fc polypeptides have been developed with one or more amino acid substitutions in the protein A binding region to match the sequence of wild-type equine IgG-Fc that binds protein A. May equine IgG2-Fc variant F(203)Y (SEQ ID NO: 71) be obtained; equine IgG2-Fc variant A(15)T/F(203)Y (SEQ ID NO: 72); equine IgG5-Fc variant V(199)L/E(200)Y (SEQ ID NO: 75); and an equine IgG6-Fc I(199)L/R(200)H/H(201)N/T(202)H variant (SEQ ID NO: 76) with increased protein A binding.

[00179] In order to potentially reduce the binding of C1q to equine IgG1-Fc, IgG3-Fc, IgG4-Fc and IgG7-Fc, and/or potentially reduce the complement-mediated immune response, variants of equine IgG1-Fc, IgG3 polypeptides can be produced -Fc, IgG4-Fc and IgG7-Fc having a Lys substitution with any amino acid other than Lys at a position corresponding to position 87 in SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO : 69, respectively. These amino acid substitutions were determined after protein sequence analysis and three-dimensional modeling of the structure of equine IgG1-Fc, IgG3-Fc, IgG4-Fc and IgG7-Fc in comparison with equine IgG2-Fc, IgG5-Fc and IgG6-Fc, which are known to be , do not activate complement. For example, the horse IgG1-Fc K(87)S variant (SEQ ID NO: 70), the horse IgG 3-Fc K(87)S variant (SEQ ID NO: 73), the horse IgG4-Fc K(87) variant )S (SEQ ID NO: 74) and the equine IgG7-Fc variant K(87)S (SEQ ID NO: 77).

[00180] The binding of any variant of equine IgG-Fc to protein A and/or C1q can be determined and compared with the binding of another IgG-Fc to protein A and/or C1q (e.g., wild type of the corresponding equine IgG-Fc, wild type type or variant of another equine IgG-Fc or wild type or variant of another companion animal IgG-Fc, etc.). The binding assay described in Example 1 can be used.

Example 3

Variant of feline IgG-Fc polypeptides with reduced complement fixation

[00181] Each of the three subtypes of feline IgG, IgG1a-Fc (SEQ ID NO: 80 or SEQ ID NO: 117), IgG1b-Fc (SEQ ID NO: 81 or SEQ ID NO: 118) and IgG2-Fc (SEQ ID NO: 118) NO: 16) binds to protein A. However, only feline IgG2-Fc has weak or undetectable binding to C1q, while feline IgG1a-Fc, IgG1b-Fc bind to C1q. To potentially reduce binding to C1q and/or potentially reduce the complement-mediated immune response, feline IgG1a-Fc and IgG1b-Fc polypeptide variants have been developed.

[00182] Table 8 below shows the protein A and C1q binding characteristics of the feline IgG-Fc subtypes. Notably, none of the wild-type feline IgG-Fc subtypes both lack C1q binding and have protein A binding.

[00183] Table 8.

Wild-type feline IgG-Fc Protein A binding Binding to C1q IgG1a-Fc + + IgG1b-Fc + + IgG2-Fc + -

(-) indicates low or undetectable binding activity.

[00184] In order to potentially reduce the binding of C1q to feline IgG1a-Fc and IgG1b-Fc and/or potentially reduce the complement-mediated immune response, variants of the feline IgG1a-Fc and IgG1b-Fc polypeptides can be produced having a Pro substitution of any amino acid , except Pro, in a position corresponding to position 198 in SEQ ID NO: 80 or SEQ ID NO: 81, respectively. These amino acid substitutions were identified after protein sequence analysis and 3D structural modeling of feline IgG1a-Fc and IgG1b-Fc in comparison with feline IgG2-Fc, which does not activate complement. For example, a feline IgG1a-Fc P(198)A variant (SEQ ID NO: 82) and a feline IgG1b-Fc P(198)A variant (SEQ ID NO: 83) can be obtained.

[00185] The binding of any variant feline IgG-Fc to C1q can be determined and compared with the binding of another IgG-Fc to C1q (e.g., wild type of the corresponding feline IgG-Fc, wild type or variant of another feline IgG-Fc or wild type or IgG-Fc variant of another companion animal, etc.). The binding assay described in Example 1 can be used.

Example 4

Canine and feline IgG-Fc polypeptide variants for heterodimeric proteins

[00186] To enable the production of a canine or feline bispecific antibody or bifunctional protein fused to a canine or feline Fc using a knob-valley heterodimerization method, pairing studies were conducted between variants of canine and feline IgG-Fc polypeptides.

[00187] Amino acid substitution of threonine at position corresponding to position 138 of canine IgG-A (SEQ ID NO: 1), at position corresponding to position 137 of canine IgG-B-Fc (SEQ ID NO: 2), at position corresponding to position 137 canine IgG-C-Fc (SEQ ID NO: 3), or at a position corresponding to position 138 of canine IgG-D-Fc (SEQ ID NO: 4), on a tyrosine (T138Y or T137Y) can be introduced into one Fc chain ( heterodimer chain 1). Examples of amino acid sequences for canine IgG-A-Fc, IgG-B-Fc, IgG-C-Fc, and IgG-D-Fc heterodimeric chain 1 variants are SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12 and SEQ ID NO: 14, respectively.

[00188] Amino acid substitution of tyrosine at position corresponding to position 181 of canine IgG-A (SEQ ID NO: 1), at position corresponding to position 180 of canine IgG-B-Fc (SEQ ID NO: 2), at position corresponding to position 180 canine IgG-C-Fc (SEQ ID NO: 3), or at a position corresponding to position 181 of canine IgG-D-Fc (SEQ ID NO: 4), a threonine (Y181T or Y180T) may be introduced into the second Fc chain ( heterodimeric chain 2). Examples of amino acid sequences for canine IgG-A-Fc, IgG-B-Fc, IgG-C-Fc, and IgG-D-Fc heterodimeric chain 2 variants are SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13 , and SEQ ID NO: 15, respectively.

[00189] A second option for pairing between heterodimeric chains 3 and 4 of canine IgG-Fc was also investigated. Amino acid substitution of threonine for tryptophan at position corresponding to position 138 of canine IgG-A (SEQ ID NO: 1) or canine IgG-D (SEQ ID NO: 4) (T138W), or at position corresponding to position 137 of canine IgG-Fc- B (SEQ ID NO: 2) or canine IgG-Fc-c (SEQ ID NO: 3) (T137W) can be introduced into a single Fc chain (heterodimeric chain 3). Examples of amino acid sequences for canine IgG-A-Fc, IgG-B-Fc, IgG-C-Fc, and IgG-D-Fc heterodimer chain 3 variants are SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113 and SEQ ID NO: 115.

[00190] Amino acid substitution of threonine to serine at position 138, leucine to alanine at position 140, and tyrosine to threonine at position 181 of canine IgG-A (SEQ ID NO: 1) or IgG-D (SEQ ID NO: 4) (T138S, L140A, Y181T), or threonine to serine at position corresponding to position 137, leucine to alanine at position corresponding to position 139, and tyrosine to threonine at position corresponding to position 180 of canine IgG-B -Fc (SEQ ID NO: 2) or IgG-C (SEQ ID NO: 3) (T137S, L139A, Y180T) may be introduced into the second Fc chain (heterodimeric chain 4). Examples of the amino acid sequences of the canine IgG-A-Fc, IgG-B-Fc, IgG-C-Fc and IgG-D-Fc heterodimer chain variants 4 are SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114 and SEQ ID NO: 116.

[00191] Amino acid substitution of threonine for tryptophan at position corresponding to position 154 of feline IgG2 (SEQ ID NO: 16), feline IgG1a-Fc (SEQ ID NO: 80 or SEQ ID NO: 117) or feline IgG1b-Fc (SEQ ID NO : 81 or SEQ ID NO: 118) (T154W), can be introduced into one Fc chain (heterodimeric chain 1). Exemplary amino acid sequences of feline IgG2-Fc, IgG1a-Fc, and IgG1b-Fc heterodimeric chain 1 variants are SEQ ID NO: 119, SEQ ID NO: 121, and SEQ ID NO: 123, respectively.

[00192] Amino acid substitution of threonine to serine at position 154, leucine to alanine at position 156, and tyrosine to threonine at position 197 of feline IgG2-Fc (SEQ ID NO: 16), IgG-1a (SEQ ID NO: 80 or SEQ ID NO: 117) or IgG-1b-Fc (SEQ ID NO: 81 or SEQ ID NO: 118) (T154S, L156A, Y197T), can be introduced into the second Fc chain (heterodimeric chain 4). Exemplary amino acid sequences of feline IgG2-Fc, IgG1a-Fc, and IgG1b-Fc heterodimeric chain 4 variants are SEQ ID NO: 120, SEQ ID NO: 122, and SEQ ID NO: 124.

[00193] Pairs between canine IgG-Fc heterodimeric chain variants 1 and 2, pairs between canine IgG-Fc heterodimeric chain variants 3 and 4, or Pairings between feline IgG-Fc heterodimeric chain variants 1 and 2 may promote Fc chain heterodimerization and prevent or reduce homodimerization of Fc chains. Heterodimeric chain 1 of one canine IgG subtype can be combined with heterodimeric chain 2 of the same or another canine IgG subtype. Heterodimeric chain 3 of one canine IgG subtype can be combined with heterodimeric chain 4 of the same or another canine IgG subtype. Heterodimeric chain 1 of one feline IgG subtype can be combined with heterodimeric chain 2 of the same or another feline IgG subtype. The design may allow dimerization of canine or feline bispecific antibodies. In addition, two different peptides or proteins or a combination of different proteins can be fused to heterodimeric Fc chains. For example, a GLP1 and glucagon dual molecule may be created using canine IgG-Fc heterodimeric chain variants or feline IgG-Fc heterodimeric chain variants, e.g., a molecule in which the GLP1 polypeptide is combined (e.g., SEQ ID NO: SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90 or SEQ ID NO: 91) fused to canine IgG-D-Fc heterodimeric chain 1 variant ( e.g., SEQ ID NO: 14), and a glucagon polypeptide (e.g., SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, or SEQ ID NO: 95) fused to a canine IgG-D heterodimer chain 2 variant -Fc (eg SEQ ID NO: 15).

Example 5

GLP1 fusion proteins

[00194] The amino acid sequence of GLP1 is conserved in humans, cats, dogs and horses, as well as among other species. The proteolysis products of GLP1 (e.g., GLP1 (amino acids 7-37) (SEQ ID NO: 85) are rapidly degraded by dipeptidyl peptidase-4 (DPP-4) and are known to have a short serum half-life of a couple of minutes.

[00195] Research has been conducted to create contiguous polypeptides containing at least one GLP1 polypeptide and feline, canine or equine IgG-Fc polypeptides have been investigated to create GLP1 fusion proteins having a long lifetime. The following designs have been developed:

formula (I): GLP1A-L1-Fc;

formula (II): Fc-L1-GLP1A; or

formula (III): GLP1A-L1-Fc-L2-GLP1B.

Where GLP1A is the first GLP1 polypeptide, GLP1B is the second GLP1 polypeptide, L1 and L2 are linkers; and Fc is an IgG-Fc polypeptide from a companion animal.

[00196] GLP1 was modified to confer resistance to DPP-4 by replacing the alanine with glycine or serine at a position corresponding to position 8 of wild type GLP1 (7-37) (SEQ ID NO: 85). The minimal sequence of wild-type GLP1(7-37) (SEQ ID NO: 87) for binding to the N-terminal domain of feline mature GLP1R (SEQ ID NO: 49) was analyzed using 3D modeling of the protein complex. Based on this modeling, the two C-terminal amino acids were removed from DPP-4-resistant GLP1 to generate the polypeptides GLP1-S8(7-35) (SEQ ID NO: 86) and GLP1-G8(7-35) (SEQ ID NO: 87).

[00197] GLP1 polypeptides, when located at the C-terminus of the construct, such as in formulas II and III, are not subject to degradation by DPP-4. Thus, substitution of alanine for glycine or serine is not necessary for GLP1 polypeptides located at the C-terminus. Accordingly, wild type GLP1(7-37) (SEQ ID NO: 85) can be used at the C-terminus of the construct.

[00198] The linker may be a flexible, unstructured linker, such as a glycine- and serine-rich linker. The C-terminus of a continuous polypeptide may be extended by a flexible sequence. The extension may contain a glycine residue (SEQ ID NO: 88), two glycine residues (SEQ ID NO: 89), three glycine residues (SEQ ID NO: 90), four glycine residues (SEQ ID NO: 91), five glycine residues ( SEQ ID NO: 92), six glycine residues (SEQ ID NO: 93), seven glycine residues (SEQ ID NO: 94), eight glycine residues (SEQ ID NO: 95) or more glycine residues.

Example 6

GLP1 and feline IgG-Fc fusion proteins

[00199] Nucleotide sequences encoding (1) a continuous polypeptide of Formula I containing a signal sequence, GLP1-G8 (7-35) (SEQ ID NO: 87), a flexible linker and wild-type feline IgG2-Fc (ssGLP1-G8_I_WTfeIgG2; SEQ ID NO: 96); and (2) a continuous polypeptide of formula III containing the signal sequence, GLP1-G8 (7-35) (SEQ ID NO: 87), GLP1 (7-35) (SEQ ID NO: 89), two flexible linkers, 2G- C-terminal extension and wild-type feline IgG2-Fc (ssGLP1-G8/GLP1-2G_III_WTfeIgG2; SEQ ID NO: 97) were synthesized and cloned into separate vectors for expression in mammalian cells. Wild-type feline IgG2-Fc (SEQ ID NO: 16) was selected based on its low or absent C1q binding to reduce complement activity and protein A binding for ease of purification.

[00200] The resulting vectors were individually transfected into CHO cells. The supernatant containing continuous polypeptides without signal peptide (SEQ ID NOs: 24 and 23) was collected and filtered. Both proteins were affinity purified using a Protein A column (CaptivA® Protein A Affinity Resin, Repligen). Using gel filtration HPLC, the proteins were determined to be monomeric. However, SDS-PAGE analysis showed that the percentage of both continuous polypeptides migrated to the same position in the gel in the absence and presence of reducing agent (DTT) (Figure 2A). This result suggests that the hinge region of wild-type feline IgG2-Fc, which has only one pair of cysteine residues, may be insufficient to form an effective disulfide bond.

[00201] Three-dimensional protein modeling analysis of several hinge orthologs was used to determine the location of exemplary modifications of the feline IgG2 hinge region to increase disulfide bond formation. To increase the formation of disulfide bonds in the hinge region of feline IgG2, its sequence can be changed by replacing an amino acid with cysteine. For example, a variant of feline IgG2-Fc (SEQ ID NO: 17), having a modified hinge region, was obtained by replacing Gly with Cys at a position corresponding to position 14 in SEQ ID NO: 16. The corresponding continuous polypeptides ssGLP1-G8_I_VARfeIgG2 (SEQ ID NO: 39) and ssGLP1-G8/GLP1-2G_III_WTfeIgG2 (SEQ ID NO: 38), containing the feline IgG-Fc variant SEQ ID NO: 17, were designed, expressed in CHO cells and purified by protein A chromatography. the sequences of these secreted proteins after cleavage of the signal sequence are SEQ ID NO: 26 and 25, respectively. SDS-PAGE analysis of the feline IgG2 variant constructs showed a decrease in the amount of protein in the lower molecular weight band in the absence of a reducing agent compared to the wild-type feline IgG2 constructs (compare Figure 2B with Figure 2A). These results indicate that covalent pairing between Fc polypeptides was improved for both constructs with the feline IgG2 variants.

[00202] In addition, differential scanning fluorimetry was used to evaluate the stability of continuous polypeptides at different pH based on the average melting point temperature (n=3) (Table 9, below). The increased stability of the feline IgG2 hinge region variant is most pronounced at pH 6. For example, constructs containing the feline IgG2 variant (SEQ ID NOs: 25 and 26) had a higher Tm at pH 6 (56.9 and 59.7°C) than the corresponding wild-type feline IgG2 constructs (SEQ ID NOs: 23 and 24), which had Tm of 55.2 and 56.9°c, respectively.

[00203] Table 9.

Construction (10 mcg) Average melting point (Tm°C) (n=3) pH 3 pH 4 pH 5 pH 6 pH 7 pH 8 GLP1-G8/GLP1-2G_III_WTfeIgG2 (SEQ ID NO:23) NK NK NK 55.2 55.7 54.2 GLP1-G8_I_WTfeIgG2 (SEQ ID NO:24) NK NK 48.5 56.9 59.9 59 GLP1-G8/GLP1-2G_III_WTfeIgG2 (SEQ ID NO:25) NK NK NK 56.9 55 52.5 GLP1-G8_I_VARfeIgG2 (SEQ ID NO:26) NK NK 53.1 59.7 59.9 58.2

NC=no curve because no clear transition point was found.

[00204] Continuous polypeptides of formulas I, II, and III containing GLP1-S8 (7-35) (SEQ ID NO: 86) instead of GLP1-G8 (7-35) (SEQ ID NO: 87) may be similar manner developed and obtained. For example, ssGLP1-S8_I_WTfeIgG2 (SEQ ID NO: 40), GLP1-S8_I_WTfeIgG2 (SEQ ID NO: 28), ssGLP1-S8/GLP1-3G_III_WTfeIgG2 (SEQ ID NO: 37) and GLP1-S8/GLP1-3G_III_WTfeIgG2 ( SEQ ID NO: 27). Similar constructs having a variant instead of wild type feline IgG-Fc, such as GLP1-S8_I_VARfeIgG2, GLP1-S8_I_VARfeIgG2, GLP1-S8/GLP1-2G_III_VARfeIgG2 and GLP1-S8/GLP1-3G_III_VARfeIgG2, can also be generated.

[00205] Although feline IgG2-Fc was used in this example, continuous polypeptides of formulas I, II and III can be designed and produced containing feline IgG1a-Fc or IgG1b-Fc instead of IgG2. For example, similar continuous polypeptides comprising wild-type feline IgG1a-Fc, wild-type feline IgG1b-Fc, variant feline IgG1a-Fc, or variant feline IgG1b-Fc (SEQ ID NOs: 80-83, respectively) can be designed and produced.

Example 7

GLP1 and canine IgG-Fc fusion proteins

[00206] Various continuous polypeptides of Formulas I, II, III containing GLP1 variant and canine IgG-Fc can be designed and produced. For example, a canine IgG-D-Fc variant (eg, SEQ ID NO: 7 or SEQ ID NO: 62) may be selected based on its low or no binding to C1q to reduce complement activity and binding to protein A for ease of purification. In addition, a flexible, unstructured linker such as a glycine and/or a serine-rich linker may be used.

[00207] GLP1-G8_I_VARcaIgGD (SEQ ID NO: 30) and GLP1-S8_I_VARcaIgGD (SEQ ID NO: 32) are examples of continuous polypeptides of Formula I containing (1) GLP1-G8 (7-35) or GLP1-S8 (7 -35), (2) a flexible linker, and (3) a canine IgG-D-Fc variant (eg, SEQ ID NO: 7). GLP1-G8/GLP1-3G_III_VARcaIgGD (SEQ ID NO: 29) and GLP1-S8/GLP1-3G_III_VARcaIgGD (SEQ ID NO: 31) are continuous polypeptides of formula III containing (1) GLP1-G8 (SEQ ID NO: 87) or GLP1-S8 (SEQ ID NO: 86), (2) GLP1 (7-35) (SEQ ID NO: 61), (3) two flexible linkers, (4) C-terminal 3G extension, and (5) Canine IgG-D-Fc variant.

[00208] Continuous polypeptides can be designed with a signal sequence, another GLP1 polypeptide (eg, SEQ ID NO: 85, 86, 87, 98 or 99) or various modifications in canine IgG-Fc. Examples with such variations include ssGLP1-S8/GLP1-2G_III_VARcaIgGD (SEQ ID NO: 41), ssGLP1-G8/GLP1-2G_III_VARcaIgGD (SEQ ID NO: 42), ssGLP1-S8/GLP1-3G_III_VARcaIgGD (SEQ ID NO: 43), GLP1-S8/GLP1-2G_III_VARcaIgGD (SEQ ID NO: 105), and GLP1-G8/GLP1-2G_III_VARcaIgGD (SEQ ID NO: 106).

[00209] Additionally, the continuous polypeptides of Formulas I, II, and III may contain wild-type or wild-type canine IgG-D or a variant of canine IgG-A, IgG-B, or IgG-C instead of a canine IgG-D variant. For example, similar continuous polypeptides can be designed and produced with canine IgG-A-Fc, IgG-B-Fc, wild-type IgG-C-Fc, or IgG-D-Fc (e.g., SEQ ID NO: 1, 2, 3, or 4, respectively). Additional examples include continuous polypeptides comprising a canine IgG-A-Fc variant (e.g., SEQ ID NO: 5 or 60), a canine IgG-B-Fc variant (e.g., SEQ ID NO: 78), or a canine IgG-C-variant Fc (eg SEQ ID NO: 6, 61, 79 or 84).

[00210] GLP1-G8/GLP1-3G_III_VARcaIgGD (SEQ ID NO: 29) and GLP1-G8_I_VARcaIgGD (SEQ ID NO: 30) were expressed separately in CHO cells, and the supernatant containing the proteins was collected and filtered. Both continuous polypeptides were purified by affinity chromatography on a Protein A column. The SDS-PAGE profiles of the two continuous polypeptides were compared in the absence and presence of a reducing agent (DTT), and the results indicated that the disulfide bonds between the Fc polypeptides were efficiently formed in both polypeptides (data not shown).

Example 8

GLP1 and equine IgG-Fc fusion proteins

[00211] Various continuous polypeptides of Formulas I, II, III containing GLP1 variant and equine IgG-Fc can be designed and produced. For example, a canine IgG2-Fc variant (eg, SEQ ID NO: 19, 71, or 72) may be selected based on its low or no binding to C1q to reduce complement activity and binding to protein A for ease of purification. In addition, a flexible, unstructured linker such as a glycine and/or a serine-rich linker may be used.

[00212] GLP1-G8_I_VAReqIgG2 (SEQ ID NO: 34) and GLP1-S8_I_VAReqIgG2 (SEQ ID NO: 36) are examples of continuous polypeptides of Formula I containing (1) GLP1-G8 or GLP1-S8, (2) a flexible linker, and (3) an equine IgG2-Fc variant (eg, SEQ ID NO: 19). GLP1-G8/GLP1-3G_III_VAReqIgG2 (SEQ ID NO: 33) and GLP1-S8/GLP1-3G_III_VAReqIgG2 (SEQ ID NO: 35) are examples of continuous Formula III polypeptides containing (1) GLP1-G8 (7-35) ( SEQ ID NO: 87) or GLP1-S8 (7-35) (SEQ ID NO: 86), (2) GLP1 (7-35) (SEQ ID NO: 61), (3) two flexible linkers, (4) C-terminal 3G extension and (5) equine IgG-D-Fc variant.

[00213] Continuous polypeptides can be designed with a signal sequence, another GLP1 analog (eg, SEQ ID NO: 85, 86, 87, 98 or 99) or various modifications in equine IgG-Fc. Examples with such variations include ssGLP1-G8/GLP1-3G_III_VAReqIgG2 (SEQ ID NO: 44), ssGLP1-G8_I_VAReqIgG2 (SEQ ID NO: 45), ssGLP1-S8/GLP1-3G_III_VAReqIgG2 (SEQ ID NO: 46) and ssGLP1-S8_I_VA ReqIgG2 ( SEQ ID NO: 47).

[00214] In addition, the continuous polypeptides of Formulas I, II, and III may contain wild-type equine IgG2, or wild-type or variant equine IgG1, IgG3, IgG4, IgG5, IgG6, IgG7 instead of the equine IgG2 variant. For example, similar continuous polypeptides can be designed and produced with wild type equine IgG1-Fc (e.g., SEQ ID NO: 63), IgG2-Fc (e.g., SEQ ID NO: 18 or 64), IgG3-Fc (e.g., SEQ ID NO: 18 or 64) NO: NO: 65), IgG4-Fc (eg, SEQ ID NO: 66), IgG5-Fc (eg, SEQ ID NO: 67), IgG6-Fc (eg, SEQ ID NO: 68) or IgG7-Fc ( e.g. SEQ ID NO: 69). Additional examples include continuous polypeptides comprising an equine IgG1-Fc variant (e.g., SEQ ID NO: 70), an equine IgG3-Fc variant (e.g., SEQ ID NO: 73), an equine IgG4-Fc variant (e.g., SEQ ID NO: 74 ), an equine IgG5-Fc variant (e.g., SEQ ID NO: 75), an equine IgG6-Fc variant (e.g., SEQ ID NO: 76), or an equine IgG7-Fc variant (e.g., SEQ ID NO: 77).

[00215] Nucleotide sequences encoding ssGLP1-G8/GLP1-3G_III_VAReqIgG2 (SEQ ID NO: 44) and ssGLP1-G8_I_VAReqIgG2 (SEQ ID NO: 45) were synthesized and cloned into separate vectors for expression in mammalian cells. The resulting vectors were separately transfected into CHO cells. The supernatant containing continuous polypeptides after signal peptide cleavage (SEQ ID NOs: 103 and 104) was collected and filtered. Both proteins were affinity purified using a protein A column (CaptivA® Protein A Affinity Resin, Repligen). The proteins were expressed individually in CHO cells, and the supernatant containing the proteins was collected and filtered. Both continuous polypeptides were affinity purified on a Protein A column. The SDS-PAGE profiles of the two continuous polypeptides were compared in the absence and presence of a reducing agent (DTT), and the results indicated that disulfide bonds between Fc polypeptides were efficiently formed at both polypeptides (data not shown).

Example 9

Expression and purification of the N-terminal soluble domain of feline GLP1R

[00216] The N-terminal domain of feline mature GLP1R (SEQ ID NO: 49), responsible for binding GLP1 to GLP1R, was identified in the full-length amino acid sequence of feline GLP1R (SEQ ID NO: 48). Nucleotide sequences encoding (1) signal sequence, feline N-terminal domain of GLP1R, human Fc and poly-His tag (ssFeGLP1R-N-huFc_PolyHis; SEQ ID NO: 50) and (2) signal sequence, feline N-terminal domain of GLP1R , and a poly-His tag (ssFeGLP1R-N_polyHis; SEQ ID NO: 51), were synthesized and cloned into separate vectors for expression in mammalian cells. The resulting vectors were separately transfected into CHO cells. The supernatant containing the polypeptides was collected and filtered. Proteins were affinity purified using Ni-Sepharose or a protein A column (CaptivA® Protein A Affinity Resin, Repligen) for the huFc construct. Both proteins were used for functional GLP1 binding and ELISA.

Example 10

Binding kinetics of GLP1 fusion protein

[00217] The binding affinity of GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) to FeGLP1R-N-huFc_PolyHis was assessed using biolayer interferometry (Octet). Briefly, FeGLP1R-N-huFc_PolyHis was biotinylated, free unreacted biotin was removed, and the biotinylated protein was captured by streptavidin at the sensor tip. The association with different concentrations of GLP1-G8_I_VARfeIgG2 was recorded for 90 seconds. Dissociation was recorded for 600 seconds. The values of the background curve obtained using the buffer are subtracted to eliminate the influence of the background. Data were fit to a 1:1 binding model using ForteBio™ analytical software to determine k _on , k _off and K _d The dilution buffer and all required steps were as follows: 20 mM phosphate, 150 mM NaCl, pH 7.2. The K _d of binding between the feline N-terminal domain of GLP1R and GLP1-G8_I_VARfeIgG2 ranged between 8.0×10 ^-9 and 16×10 ^-9 M.

Example 11

Biological activity of GLP1 fusion protein in cell-based assay

[00218] The CHOK-1-GL1R cell line (Discoverx, cat. no. 95-0062C2), a hamster ovary cell line that overexpresses Gs-coupled human glucagon ligand peptide-1 receptors (GLP1R) on the cell surface, was used to measure cellular GLP1 activity using the cAMP Hunter Bioassay kit (Discoverx, cat. no. 95-0062Y2). Cells were seeded into a 96-well plate and incubated at 37°C, 5% CO ₂ for 24 hours. The cells were then treated with an agonist control, either human GLP1 (37 aa) (Prospec, cat. no. HOR-236) or Extendedin-4 (Discoverx, cat. no. 92-1115), or a continuous polypeptide containing the GLP1 variant, in series of 3- multiple dilutions, followed by incubation at 37°C for 30 minutes. The continuous polypeptides tested were GLP1-G8/GLP1-2G_III_VARfeIgG2 (SEQ ID NO: 25) and GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26).

[00219] When GLP1 binds to the Gs-linked GLP1R, the Gs stimulate the production of cAMP by adenylate cyclase. At the end of incubation, cAMP antibody and a cAMP detection working solution, which contains lysis buffer conjugated to a small β-galactosidase (β-GAL) fragment of cAMP and substrates, were added to the cells. Cells were incubated in the dark for 1 hour at room temperature to allow an immunocompetitive reaction to occur between endogenously generated cAMP and cAMP conjugated to a small fragment of β-galactosidase (β-gal) for cAMP-antibody binding.

[00220] At the end of the 1 hour incubation, cAMP solution A containing a large β-gal fragment, which can complement the free (unbound to antibody) small cAMP-conjugated β-gal fragment, is added to the cell lysate to form a functional enzyme. The lysate was incubated for 3–6 h in the dark at room temperature to allow β-gal to hydrolyze the substrate and generate a luminescent signal.

[00221] The more free small β-gal fragment conjugated to cAMP remains unbound, the more functional β-gal enzyme is produced. Thus, the level of the resulting signal is directly proportional to the amount of cAMP in the cell lysate. At the end of incubation, luminescence was read on a Synergy HT microplate reader (Biotek, Winooski, VT). EC50s were calculated using GraphPad Prism software (GraphPad Software, Inc. La Jolla, USA).

[00222] Figure 3 shows a graph of relative light units (RLU) versus concentration for each test sample. The EC50 are listed in Table 10 below. Both constructs, GLP1-G8/GLP1-2G_III_VARfeIgG2 (SEQ ID NO: 25) and GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26), are more active than GLP1 (7-37) and Extendin-4. GLP1-G8/GLP1-2G_III_VARfeIgG2 (SEQ ID NO: 25) is more potent than GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26), suggesting that the C-terminal GLP1 may confer additional activity.

[00223] Table 10.

Sample EC 50 (nM) GLP1 (7-37) 0.1449 Extendin-4 0.4596 GLP1-G8/GLP1-2G_III_VARfeIgG2
(SEQ ID NO: 25) 0.01751 GLP1-G8_I_VARfeIgG2
(SEQ ID NO: 26) 0.02806

Example 12

Long-term stability of GLP1 fusion protein

[00224] GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) was stored in PBS, pH 7.2, at a concentration of 1.3 mg/ml, placed in 1.5 ml Eppendorf tubes, at a temperature of 2-8°C for one year (batch 2-29-2016). GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) was also stored in PBS, pH 7.2, at a concentration of 10 mg/ml, placed in 1.5 ml Eppendorf tubes at 2-8°C for one day (lot 2 -2-2017). To assess stability, samples after storage were analyzed in a cellular assay using the same CHOK-1-GL1R cell line (Discoverx, cat. no. 95-0062C2) described in Example 11, but cellular activity was assessed using the cAMP-Glo™ Max Assay (Promega, cat. no. PAV1682).

[00225] CHOK-1-GL1R cells were seeded in a 96-well plate (Corning, cat. no. 3610) at a density of 20,000 cells per well in F-12K medium (ATCC, cat. no. 30-2004 ATCC®) supplemented with 10% heat-inactivated fetal bovine serum (Sigma, cat. no. 2868) and incubated at 37°C, 5% CO ₂ for 24 hours. Cells were then stimulated with control human GLP1 agonist (37 aa) (Prospec, cat. no. HOR-236), lot 2-20-2016 or lot 2-2-2017 in a series of 3-fold dilutions in serum-free medium followed by the addition of Complete Induction Buffer, which contains MgCl ₂ to a final concentration of 20 mM, isobutyl-l-methylxanthine (IBMX) (Sigma-Aldrich, cat. no. 17018) to a final concentration of 500 μΜ and Ro 20-1724 [4-(3-butoxy-4 -methoxy-benzyl)imidazolidone] (Sigma Aldrich, cat. # B8279) to a final concentration of 100 μΜ.

[00226] Cells were incubated at room temperature for 30 minutes. In this process, upon binding of GLP1 to Gs-bound GLP1R, Gs stimulates the production of cAMP by adenylate cyclase. At the end of incubation, cAMP Detection Solution, which contains inactive protein kinase A holoenzyme, protein kinase A substrate, and lysis buffer, is added to the cells. The plates were placed on an orbital shaker for 1-2 minutes and then incubated at room temperature (23°C) for 20 minutes. Cellular cAMP activates protein kinase A by binding its regulatory inhibitory subunit and releasing the catalytic subunits. The free catalytic subunits catalyze the transfer of the terminal phosphate of ATP to the protein kinase A substrate, consuming cellular ATP in the process. At the end of incubation, Kinase-Glo® luciferase reagent was added to the cell lysates and the plates were shaken on an orbital shaker for 2 minutes, followed by incubation in the dark at room temperature for 10 minutes.

[00227] Luciferin monooxidation was catalyzed by luciferase in the presence of Mg ²⁺ and ATP, which was present in the cell lysate, resulting in a luminescent signal proportional to the amount of ATP in the cells. At the end of the 10-minute incubation, the plate was read on a Synergy HT microplate reader (Biotek, Winooski, VT). Luminescence was proportional to the ATP level but inversely proportional to the cAMP level. Thus, as the concentration of cAMP increases, the luminescence decreases.

[00228] Figure 4 shows the results of the cellular assay as a plot of luminescence versus concentration for batch 2-29-2016 compared to batch 2-2-2017 and GLP1 (31 aa). Sample GLP1-G8_I_VARfeIgG2 retained cellular activity after storage in PBS at 2-8°C for one year.

Example 13

Serum stability of GLP1 fusion protein

[00229] GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) was stored in PBS, pH 7.2 with cat serum at 37°C for 24 hours to test serum stability in vitro. Cellular assays were performed as described in Example 12 and the results indicated that activity was maintained (data not shown). In addition, no visible degradation was observed by Western blot analysis (Figure 5).

Example 14

In vivo pharmacokinetics of GLP1 fusion protein

[00230] GLP1-G8_I_VARfeIgG2 (SEQ ID NO: 26) was administered as a single dose (2 mg/kg) by subcutaneous injection to 5 cats. Serum samples were collected before administration (time 0) and after 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours and 168 hours. The concentration of GLP1-G8_I_VARfeIgG2 in serum samples was measured using quantitative ELISA. The GLP1-G8_I_VARfeIgG2 polypeptide with a detection limit of 4 ng/ml was used as a standard. Serum concentrations of GLP1-G8_I_VARfeIgG2 were plotted against time (Figure 6). The mean serum half-life ( _t½ ) of GLP1-G8_I_VARfeIgG2 was 39 hours. The mean T _max was 22 hours, the mean C _max was 12 μg/mL, and the mean area under the curve (AUC) was approximately 950 μg μg(h)/mL.

[00231] The quantitative ELISA used anti-GLP1 antibodies (4F3, Novus Biologicals, cat. no. NBP1-97413) and HRP-conjugated goat anti-feline IgG-Fc antibodies (Bethyl Laboratories, Inc, cat. no. A20-117P) to quantify GLP1-G8_I_VARfeIgG2 in feline serum samples in in vivo pharmacokinetic studies. A 96-well plate was coated with anti-GLP1 antibodies (5 μg/ml in coating buffer, 100 μl/well). The plate was sealed and incubated overnight at 4°C. The plate was washed three times with 1xTBST (10X TBST, Teknova, catalog no. T9511) and blocking buffer was added. After removing the blocking buffer, serial dilutions of the standard and samples in blocking buffer (100 well/well) were added and the plates were incubated for 2 hours at room temperature. The plate was washed three times with 1xTBST and goat anti-feline IgG-Fc (0.1 μg/ml in blocking buffer, 100 μl/well) was added. After incubation for 1 hour at room temperature, the plates were washed 5 times with 1xTBST. TMB substrate (ScyTek, cat. no. TM1999) was added (100 μl/well) and incubated at room temperature for 1 minute. The reaction was stopped by adding 2M H ₂ SO ₄ (50 µl/well). The absorbance at 450 nm was measured, and the concentration of GLP1-G8_I_VARfeIgG2 in serum samples was calculated.

[00232] Additionally, the concentration of GLP1-G8_I_VARfeIgG2 in the same serum samples (without the addition of DPP-4 inhibitor) was assessed using a cellular activity assay. The same CHOK-1-GL1R cell line (Discoverx, cat. no. 95-0062C2) and cAMP-Glo™ Max Assay (Promega, cat. no. PAV1682) described in Example 12 were used. In this example, however, these cells were stimulated with control human GLP1 agonist (37 aa) (Prospec, cat. no. HOR-236) or feline serum samples collected pre-administration (time 0) and after 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours , 168 hours and diluted in serum-free medium (dilutions up to 5%, 0.5% and 0.05%). The concentration of GLP1-G8_I_VARfeIgG2 in each sample was calculated using SoftMax Pro 7 (Molecular Devices, Sunnyvale, CA). The average concentration of GLP1-G8_I_VARfeIgG2 for 5 cats was plotted against time (Figure 7). The mean AUC was approximately 840 mcg(h)/ml, and the mean T1 _/2 was 36 hours.

Example 15

GLP1, glucagon and IgG-Fc fusion proteins

[00233] To investigate a dual agonist of the GLP1 receptor and the glucagon receptor with a long-lasting action, continuous polypeptides were created containing a GLP1 polypeptide, a glucagon polypeptide and an IgG-Fc polypeptide and having the following constructs:

formula (IV): GLP1-L1-Fc-L2-Gluc; And

formula (V): Gluc-L1-Fc-L2-GLP1,

where GLP1 is a GLP1 polypeptide, Gluc is a glucagon polypeptide, L1 and L2 are linkers, and Fc is an Fc polypeptide.

[00234] As described above, GLP1 was modified to be resistant to DPP-4 by replacing the alanine with glycine or serine at a position corresponding to position 8 of wild type GLP1 (7-37) (SEQ ID NO: 85). In addition, DPP-4-resistant GLP1 was further modified by removing the two C-terminal amino acids to generate the polypeptide variants GLP1-S8(7-35) (SEQ ID NO: 86) and the variant GLP1-G8(7-35) (SEQ ID NO: 87).

[00235] GLP1 polypeptides, when located at the C-terminus of the construct, for example, as in formula (V), are refractory to degradation by DPP-4. Thus, substitution of alanine for glycine or serine is not necessary for GLP1 polypeptides located at the C-terminus. Accordingly, wild-type GLP1 (7-37) (SEQ ID NO: 85) can be used at the C-terminus.

[00236] The linker may be a flexible, unstructured linker, such as a glycine- and serine-rich linker. The C-terminus of a continuous polypeptide may be extended by a flexible sequence. The extension may contain a glycine residue (SEQ ID NO: 88), two glycine residues (SEQ ID NO: 89), three glycine residues (SEQ ID NO: 90), four glycine residues (SEQ ID NO: 91), five glycine residues ( SEQ ID NO: 92), six glycine residues (SEQ ID NO: 93), seven glycine residues (SEQ ID NO: 94), eight glycine residues (SEQ ID NO: 95) or more glycine residues.

[00237] The continuous polypeptide may include a wild-type glucagon polypeptide (eg, SEQ ID NO: 21) or a variant glucagon polypeptide.

[00238] The continuous polypeptide may comprise a human or companion animal IgG-Fc, such as a canine, feline, or equine. The IgG-Fc subtype used may be selected based on low or absent binding to C1q and/or binding to protein A. For example, wild type or variant human, canine, equine or feline IgG-Fc having low or absent binding to C1q may be used. and/or having binding to protein A (for example, SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 , 19, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 , 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83 or 84).

[00239] Examples of continuous polypeptides containing a GLP1 polypeptide, a glucagon polypeptide, and a feline IgG-Fc polypeptide include GLP1-G8/Gluc-3G_IV_WTfeIgG2 (SEQ ID NO: 52) and Gluc/GLP1-2G_V_WTfeIgG2 (SEQ ID NO: 53).

[00240] Examples of continuous polypeptides containing a GLP1 polypeptide, a glucagon polypeptide, and a canine IgG-Fc polypeptide include GLP1-G8/Gluc-4G_IV_VARcaIgGD (SEQ ID NO: 54) and Gluc/GLP1-3G_V_VARcaIgGD (SEQ ID NO: 55).

[00241] Examples of continuous polypeptides containing a GLP1 polypeptide, a glucagon polypeptide, and an equine IgG-Fc polypeptide include GLP1-G8/Gluc-4G_IV_VAReqIgGD (SEQ ID NO: 56) and Gluc/GLP1-3G_V_VAReqIgG2 (SEQ ID NO: 57).

[00242] Examples of continuous polypeptides comprising a GLP1 polypeptide, a glucagon polypeptide and a human IgG-Fc polypeptide include GLP1-G8/Gluc-4G_IV_huIgG4 (SEQ ID NO: 8) and Gluc/GLP1-3G_V_huIgG4 (SEQ ID NO: 59).

Example 16

Variants of IgG-Fc polypeptides to enhance disulfide bond formation at the hinge region

[00243] Additional 3D modeling of several hinge orthologs was used to modify the hinge regions of feline and horse IgG to increase disulfide bond formation. To enhance the formation of disulfide bonds in the hinge region of feline IgG, the sequence of the hinge region can be changed by replacing a lysine with a proline at position corresponding to position 16 of feline IgG2 (SEQ ID NO: 16), feline IgG1a (SEQ ID NO: 80 or SEQ ID NO : 117) or feline IgG1b (SEQ ID NO: 81 or SEQ ID NO: 118) (eg, K16P). Exemplary amino acid sequences of variant feline IgG polypeptides having a modified hinge region include SEQ ID NO: 125, SEQ ID NO: 126 and SEQ ID NO: 127.

[00244] To enhance the formation of disulfide bonds in the hinge region of equine IgG, the sequence of the hinge region can be modified by replacing cysteine with serine at a position corresponding to position 3 in equine IgG (for example, IgG2-Fc (SEQ ID NO: 129)) and/ or replacing glutamine with proline at a position corresponding to position 20 in equine IgG (e.g., IgG2-Fc (SEQ ID NO: 129) (e.g., C3S, Q20P) Examples of amino acid sequences of variant equine IgG polypeptides having a modified hinge region are included in SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 134 and SEQ ID NO: 135.

Example 17

Variants of IgG-Fc polypeptides to enhance recombinant production and/or enhanced disulfide bond formation at the hinge region

[00245] Three-dimensional modeling was used to generate variant feline and equine IgG-Fc polypeptides containing hinge region sequences from a different IgG isotype to improve production in the recombinant system and improve disulfide bond formation at the hinge region. Variant feline IgG2-Fc polypeptides can be produced that contain sequences from the hinge region of feline IgG1a or IgG1b (eg, SEQ ID NO: 125). In addition, variant equine IgG2-Fc polypeptides can be produced that contain sequences from the hinge region of equine IgG1 (eg, SEQ ID NO: 19).

[00246] The level of production of IgG-Fc variant polypeptides in a recombinant system and/or the level of disulfide bond formation at the hinge region can be determined and compared to other IgG-Fcs by SDS-PAGE analysis under reducing and non-reducing conditions (e.g. with a corresponding wild-type IgG-Fc from the same or a different isotype, or a wild-type or variant IgG-Fc from another companion animal, etc.).

--->

LIST OF SEQUENCES

<110> KINDRED BIOSCIENCES, INC.

<120> IGG-FC OPTIONS FOR VETERINARY USE

<130> 01157-0011-00PCT

<150>US 62/545,858

<151> 2017-08-15

<160> 199

<170> Patent In version 3.5

<210> 1

<211> 221

<212> Protein

<213> Unknown origin

<220>

<223> Wild type canine IgG-A-Fc, Protein A -, C1q -, CD16

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Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

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Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

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Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

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Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

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His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

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Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

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Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

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Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe

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Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

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Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

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Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

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His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

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<223> Wild type canine IgG-B-Fc, Protein A+, C1q+, CD16+

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Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

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Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

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<213> Unknown origin

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Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

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Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

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His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

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Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

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<213> Unknown origin

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<223> Wild type canine IgG-D-Fc, Protein A -, C1q -, CD16

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Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

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Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

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His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

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Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

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<223> Synthetic sequence: Canine IgG-A-Fc variant,

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Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

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Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

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Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

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His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

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Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

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Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

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Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

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Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

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<212> Protein

<213> Artificial sequence

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<223> Synthetic sequence: Canine IgG-C-Fc variant,

C1q+, Protein A+, I(21)T,

V(23)L, T(24)I

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85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 7

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-D-Fc variant,

C1q -, Protein A +, I(21)T,

R(23)L, T(25)A, E(80)G, Q(207)H

<400> 7

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 8

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-A-Fc variant,

Heterodimeric chain 1 T(138)Y

<400> 8

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Tyr Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 9

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-A-Fc variant,

Heterodimeric chain 2, Y(181)T

<400> 9

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 10

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-B-Fc variant,

Heterodimeric chain 1 T(137)Y

<400> 10

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Tyr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 11

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-B-Fc variant,

Heterodimeric chain 2, Y(180)T

<400> 11

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 12

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-C-Fc variant,

Heterodimeric chain 1 T(137)Y

<400> 12

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Tyr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 13

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-C-Fc variant,

Heterodimeric chain 2, Y(180)T

<400> 13

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 14

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-D-Fc variant,

Heterodimeric chain 1 T(138)Y

<400> 14

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Tyr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 15

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-D-Fc variant,

Heterodimeric chain 2, Y(181)T

<400> 15

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 16

<211> 237

<212> Protein

<213> Unknown origin

<220>

<223> Wild type feline IgG2-Fc, Protein A+, C1q -

<400> 16

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 17

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Feline IgG2-Fc variant,

Replacement with Cys in the hinge region, G(14)C

<400> 17

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Cys Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 18

<211> 228

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG2-Fc variant

(with hinge region from equine IgG1),

Protein A - , C1q -

<400> 18

Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly

1 5 10 15

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile

20 25 30

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

35 40 45

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

50 55 60

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

65 70 75 80

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

85 90 95

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

100 105 110

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

115 120 125

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

130 135 140

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

145 150 155 160

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

165 170 175

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

180 185 190

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

195 200 205

Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu

210 215 220

Ser Leu Gly Lys

225

<210> 19

<211> 228

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG2-Fc variant

(with hinge region from equine IgG1), C1q

-, Protein A +, A(29)T, F(217)Y

<400> 19

Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly

1 5 10 15

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile

20 25 30

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

35 40 45

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

50 55 60

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

65 70 75 80

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

85 90 95

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

100 105 110

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

115 120 125

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

130 135 140

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

145 150 155 160

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

165 170 175

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

180 185 190

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

195 200 205

Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu

210 215 220

Ser Leu Gly Lys

225

<210> 20

<211> 29

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1 variant (7-35)

<220>

<221> other signs

<222> (2)..(2)

<223> X may be G or S

<400> 20

His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

20 25

<210> 21

<211> 29

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Glucagon (Gluc)

<400> 21

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser

1 5 10 15

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr

20 25

<210> 22

<211> 39

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Extendin-4

<400> 22

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 23

<211> 325

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLP-2G_III_WTfeIgG2

<400> 23

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

50 55 60

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

65 70 75 80

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

85 90 95

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

100 105 110

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

115 120 125

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

130 135 140

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

145 150 155 160

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

165 170 175

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

180 185 190

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

195 200 205

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

210 215 220

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

225 230 235 240

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

245 250 255

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

260 265 270

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys Gly Gly Gly

275 280 285

Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val

290 295 300

Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu

305 310 315 320

Val Lys Gly Gly Gly

325

<210> 24

<211> 285

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8_I_WTfeIgG2

<400> 24

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

50 55 60

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

65 70 75 80

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

85 90 95

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

100 105 110

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

115 120 125

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

130 135 140

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

145 150 155 160

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

165 170 175

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

180 185 190

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

195 200 205

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

210 215 220

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

225 230 235 240

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

245 250 255

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

260 265 270

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

275 280 285

<210> 25

<211> 325

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLP1-2G_III_

VARfeIgG2

<400> 25

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Cys Pro Lys

50 55 60

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

65 70 75 80

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

85 90 95

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

100 105 110

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

115 120 125

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

130 135 140

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

145 150 155 160

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

165 170 175

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

180 185 190

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

195 200 205

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

210 215 220

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

225 230 235 240

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

245 250 255

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

260 265 270

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys Gly Gly Gly

275 280 285

Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val

290 295 300

Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu

305 310 315 320

Val Lys Gly Gly Gly

325

<210> 26

<211> 285

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8_I_VARfeIgG2

<400> 26

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Cys Pro Lys

50 55 60

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

65 70 75 80

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

85 90 95

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

100 105 110

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

115 120 125

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

130 135 140

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

145 150 155 160

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

165 170 175

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

180 185 190

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

195 200 205

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

210 215 220

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

225 230 235 240

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

245 250 255

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

260 265 270

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

275 280 285

<210> 27

<211> 327

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8/GLP1-3G_III_

WTfeIgG2

<400> 27

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro

50 55 60

Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe

65 70 75 80

Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val

85 90 95

Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile

100 105 110

Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro

115 120 125

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro

130 135 140

Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val

145 150 155 160

Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala

165 170 175

Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln

180 185 190

Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly

195 200 205

Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro

210 215 220

Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp

225 230 235 240

Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp

245 250 255

Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His

260 265 270

Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys Gly Gly

275 280 285

Gly Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp

290 295 300

Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp

305 310 315 320

Leu Val Lys Gly Gly Gly Gly

325

<210> 28

<211> 286

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8_I_WTfeIgG2

<400> 28

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro

50 55 60

Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe

65 70 75 80

Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val

85 90 95

Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile

100 105 110

Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro

115 120 125

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro

130 135 140

Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val

145 150 155 160

Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala

165 170 175

Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln

180 185 190

Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly

195 200 205

Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro

210 215 220

Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp

225 230 235 240

Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp

245 250 255

Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His

260 265 270

Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

275 280 285

<210> 29

<211> 323

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLP1-3G_III_

VARcaIgGD

<400> 29

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys Pro Val Pro

50 55 60

Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu

85 90 95

Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

100 105 110

Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

130 135 140

Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu

145 150 155 160

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

165 170 175

Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser

180 185 190

Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

195 200 205

Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser

210 215 220

Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

225 230 235 240

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp

245 250 255

Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

260 265 270

Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly

275 280 285

Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

290 295 300

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

305 310 315 320

Gly Gly Gly

<210> 30

<211> 282

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8_I_VARcaIgGD

<400> 30

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro

50 55 60

Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu

85 90 95

Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

100 105 110

Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

130 135 140

Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu

145 150 155 160

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

165 170 175

Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser

180 185 190

Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

195 200 205

Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser

210 215 220

Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

225 230 235 240

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp

245 250 255

Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

260 265 270

Asp Leu Ser Leu Ser His Ser Pro Gly Lys

275 280

<210> 31

<211> 323

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8/GLP1-3G_III_

VARcaIgGD

<400> 31

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys Pro Val Pro

50 55 60

Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu

85 90 95

Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

100 105 110

Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

130 135 140

Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu

145 150 155 160

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

165 170 175

Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser

180 185 190

Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

195 200 205

Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser

210 215 220

Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

225 230 235 240

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp

245 250 255

Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

260 265 270

Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly

275 280 285

Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

290 295 300

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

305 310 315 320

Gly Gly Gly

<210> 32

<211> 282

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8_I_VARcaIgGD

<400> 32

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro

50 55 60

Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu

85 90 95

Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

100 105 110

Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

130 135 140

Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu

145 150 155 160

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

165 170 175

Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser

180 185 190

Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

195 200 205

Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser

210 215 220

Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

225 230 235 240

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp

245 250 255

Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

260 265 270

Asp Leu Ser Leu Ser His Ser Pro Gly Lys

275 280

<210> 33

<211> 318

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLPL1-3G_III_

VAReqIgG2

<400> 33

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala

275 280 285

Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala

290 295 300

Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

305 310 315

<210> 34

<211> 277

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8_I_VAReqIgG2

<400> 34

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys

275

<210> 35

<211> 318

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8/GLP1-3G_III_

VAReqIgG2

<400> 35

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala

275 280 285

Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala

290 295 300

Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

305 310 315

<210> 36

<211> 277

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8_I_VAReqIgG2

<400> 36

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys

275

<210> 37

<211> 346

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-S8/GLP1-3G_III_

WTfeIgG2

<400> 37

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly

65 70 75 80

Glu Gly Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val

85 90 95

Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr

100 105 110

Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn

115 120 125

Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys

130 135 140

Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

145 150 155 160

Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys

165 170 175

Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile

180 185 190

Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro

195 200 205

Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu

210 215 220

Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr

225 230 235 240

Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu

245 250 255

Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg

260 265 270

Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu

275 280 285

Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly

290 295 300

Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe

305 310 315 320

Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe

325 330 335

Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

340 345

<210> 38

<211> 344

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8/GLP1-2G_III_

VARfeIgG2

<400> 38

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

50 55 60

Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu

65 70 75 80

Cys Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe

85 90 95

Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro

100 105 110

Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val

115 120 125

Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr

130 135 140

Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

145 150 155 160

Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys

165 170 175

Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser

180 185 190

Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro

195 200 205

Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile

210 215 220

Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly

225 230 235 240

Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp

245 250 255

Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser

260 265 270

His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala

275 280 285

Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

290 295 300

Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr

305 310 315 320

Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile

325 330 335

Ala Trp Leu Val Lys Gly Gly Gly

340

<210> 39

<211> 304

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8_I_VARfeIgG2

<400> 39

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

50 55 60

Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu

65 70 75 80

Cys Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe

85 90 95

Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro

100 105 110

Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val

115 120 125

Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr

130 135 140

Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

145 150 155 160

Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys

165 170 175

Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser

180 185 190

Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro

195 200 205

Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile

210 215 220

Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly

225 230 235 240

Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp

245 250 255

Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser

260 265 270

His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala

275 280 285

Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

290 295 300

<210> 40

<211> 305

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-S8_I_WTfeIgG2

<400> 40

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly

65 70 75 80

Glu Gly Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val

85 90 95

Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr

100 105 110

Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn

115 120 125

Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys

130 135 140

Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

145 150 155 160

Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys

165 170 175

Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile

180 185 190

Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro

195 200 205

Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu

210 215 220

Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr

225 230 235 240

Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu

245 250 255

Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg

260 265 270

Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu

275 280 285

Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly

290 295 300

Lys

305

<210> 41

<211> 340

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8/GLP1-2G_III_

VARcaIgGD

<400> 41

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

50 55 60

Gly Gly Ser Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro

65 70 75 80

Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys

85 90 95

Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val

100 105 110

Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe

115 120 125

Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln

130 135 140

Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His

145 150 155 160

Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile

165 170 175

Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln

180 185 190

Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu

195 200 205

Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe

210 215 220

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro

225 230 235 240

Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser

245 250 255

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln

260 265 270

Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His

275 280 285

Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly

290 295 300

Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser

305 310 315 320

Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val

325 330 335

Lys Gly Gly Gly

340

<210> 42

<211> 340

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8/GLP1-2G_III_

VARcaIgGD

<400> 42

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

50 55 60

Gly Gly Ser Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys Pro

65 70 75 80

Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys

85 90 95

Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val

100 105 110

Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe

115 120 125

Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln

130 135 140

Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His

145 150 155 160

Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile

165 170 175

Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln

180 185 190

Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu

195 200 205

Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe

210 215 220

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro

225 230 235 240

Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser

245 250 255

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln

260 265 270

Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His

275 280 285

Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly

290 295 300

Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser

305 310 315 320

Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val

325 330 335

Lys Gly Gly Gly

340

<210> 43

<211> 342

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-S8/GLP1-3G_III_

VARcaIgGD

<400> 43

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys

65 70 75 80

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

85 90 95

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys

100 105 110

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

115 120 125

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

130 135 140

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

145 150 155 160

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

165 170 175

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

180 185 190

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

195 200 205

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

210 215 220

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

225 230 235 240

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

245 250 255

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

260 265 270

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn

275 280 285

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly

290 295 300

Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val

305 310 315 320

Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu

325 330 335

Val Lys Gly Gly Gly Gly

340

<210> 44

<211> 337

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8/GLP1-3G_III_

VAReqIgG2

<400> 44

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu

65 70 75 80

Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp

85 90 95

Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn

100 105 110

Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn

115 120 125

Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn

130 135 140

Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp

145 150 155 160

Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro

165 170 175

Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val

180 185 190

Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser

195 200 205

Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile

210 215 220

Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr

225 230 235 240

Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr

245 250 255

Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe

260 265 270

Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr

275 280 285

Asp Ile Ser Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly

290 295 300

Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu

305 310 315 320

Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly

325 330 335

Gly

<210> 45

<211> 298

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8_I_VAReqIgG2

<400> 45

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Ser Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His

65 70 75 80

Ser Lys Phe Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro

85 90 95

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val

100 105 110

Val Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val

115 120 125

Asp Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln

130 135 140

Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln

145 150 155 160

Asp Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly

165 170 175

Val Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser

180 185 190

Arg Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala

195 200 205

Lys Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro

210 215 220

Asp Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly

225 230 235 240

Lys Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe

245 250 255

Leu Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu

260 265 270

Ser Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

275 280 285

Lys Thr Asp Ile Ser Glu Ser Leu Gly Lys

290 295

<210> 46

<211> 337

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-S8/GLP1-3G_III_

VAReqIgG2

<400> 46

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu

65 70 75 80

Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp

85 90 95

Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn

100 105 110

Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn

115 120 125

Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn

130 135 140

Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp

145 150 155 160

Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro

165 170 175

Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val

180 185 190

Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser

195 200 205

Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile

210 215 220

Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr

225 230 235 240

Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr

245 250 255

Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe

260 265 270

Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr

275 280 285

Asp Ile Ser Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly

290 295 300

Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu

305 310 315 320

Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly

325 330 335

Gly

<210> 47

<211> 298

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-S8_I_VAReqIgG2

<400> 47

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Ser Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His

65 70 75 80

Ser Lys Phe Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro

85 90 95

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val

100 105 110

Val Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val

115 120 125

Asp Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln

130 135 140

Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln

145 150 155 160

Asp Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly

165 170 175

Val Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser

180 185 190

Arg Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala

195 200 205

Lys Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro

210 215 220

Asp Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly

225 230 235 240

Lys Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe

245 250 255

Leu Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu

260 265 270

Ser Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

275 280 285

Lys Thr Asp Ile Ser Glu Ser Leu Gly Lys

290 295

<210> 48

<211> 757

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Feline receptor

glucagon-like peptide-1 (GLP1R)

<400> 48

Met Gly Leu Val Ala Pro Val Val Leu Leu His Gln Asp Asp Glu Glu

1 5 10 15

His Gly Gln Asp Glu Gly Pro Glu Asp Gly Ser Gly Tyr Leu Leu Gly

20 25 30

Thr Leu Thr Arg Phe Ser Ser Asp Phe Asp Ser Ala Pro Glu Val Ile

35 40 45

Leu Ala Pro Asp Asp Gln Leu Gln Leu Pro His Pro Ser Ser Arg Glu

50 55 60

Asn Phe Trp Ala Arg Thr Gly Leu Cys Ala Glu Ser Phe Leu Leu Arg

65 70 75 80

Pro Val Gly Pro Val Gly Pro Val Met Gly Trp Ser Glu Gly Phe His

85 90 95

Lys Arg Asn Ser Arg Gln Glu Phe Leu Arg Arg Arg Leu Phe Ala Gly

100 105 110

Gly Leu Cys Ala Ala Ser Thr Gln Glu Ser Arg Asn Arg Cys Ser Ser

115 120 125

Arg Gly Cys Lys Ser Ser Pro Ala Asp Cys Pro Glu Leu Asp Arg Thr

130 135 140

Gln His Leu Gly Asn Ser Val Gly Pro Ile Gln Ala Ala His Gln Glu

145 150 155 160

Leu Ala Leu Gly Ala Gly Gly Pro Gly Asp Glu Cys Gln Cys Cys Ser

165 170 175

Val Ser Asn Ser Leu Phe Ile Pro Glu Pro Gln Ser Thr Cys Pro Tyr

180 185 190

Asn Gly Tyr Thr Ser Trp Pro Leu Glu Gly Asn Leu Arg Val Ala Cys

195 200 205

Ala Pro Pro Pro Pro Pro Pro Ala Arg Thr Leu Phe Gly Gly Ser Arg

210 215 220

Arg Gly Ala Val Asp Lys Lys Ala Gly Gly Gly Asn Arg Ser Pro Gly

225 230 235 240

Gly Gly Ala Gly Thr Gly Glu Phe Gly Ala Pro Gly Ala Gly Gly Gly

245 250 255

Leu Gly Arg Arg Pro Glu Val Gly Ala Trp Thr Ala Ala Glu Gly Thr

260 265 270

Asn Pro Ala Asp Leu Ala Ser Ser Pro Pro Pro Pro Ser Thr Arg Pro

275 280 285

Pro Ala Ala Pro Arg Pro Pro Cys Ala Asp Phe Cys Ala Ala Ser Pro

290 295 300

Gln Thr Thr Phe Pro Thr Pro Ser Pro Arg Arg Pro Leu Pro Ala Ser

305 310 315 320

Gly Gly Ala Thr Val Ser Leu Ser Glu Thr Val Gln Lys Trp Arg Glu

325 330 335

Tyr Arg His Gln Cys Gln Arg Phe Leu Thr Glu Ala Pro Pro Pro Ala

340 345 350

Thr Gly Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys Trp Pro

355 360 365

Asp Gly Leu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp Tyr Leu

370 375 380

Pro Trp Ala Ser Ser Val Leu Gln Gly His Val Tyr Arg Phe Cys Thr

385 390 395 400

Ala Glu Gly Leu Trp Leu Arg Gln Asp Asn Ser Ser Leu Pro Trp Arg

405 410 415

Asn Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser Ser Pro

420 425 430

Glu Glu Gln Leu Leu Ser Phe Ser Ile Ile Tyr Thr Val Gly Tyr Thr

435 440 445

Leu Ser Phe Ser Ala Leu Val Ile Ala Ser Ala Ile Leu Leu Ser Phe

450 455 460

Arg His Leu His Cys Thr Arg Asn Tyr Ile His Leu Asn Leu Phe Ala

465 470 475 480

Ser Phe Ile Leu Arg Ala Leu Ser Val Phe Ile Arg Asp Ala Val Leu

485 490 495

Lys Trp Met Tyr Ser Thr Ala Pro Gln Gln His Gln Trp Asp Gly Leu

500 505 510

Leu Ser Tyr Gln Asp Ser Leu Gly Cys Arg Leu Val Phe Leu Leu Met

515 520 525

Gln Tyr Cys Val Ala Ala Asn Tyr Tyr Trp Leu Leu Val Glu Gly Val

530 535 540

Tyr Leu Tyr Thr Leu Leu Ala Phe Ser Val Phe Ser Glu Gln Arg Ile

545 550 555 560

Phe Arg Leu Tyr Leu Ser Ile Gly Trp Gly Val Pro Leu Leu Phe Val

565 570 575

Ile Trp Gly Ile Val Lys Tyr Leu Tyr Glu Asp Glu Gly Cys Trp Thr

580 585 590

Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile Ile Arg Leu Pro Ile Leu

595 600 605

Phe Ala Ile Gly Val Asn Phe Leu Ile Phe Val Arg Val Ile Cys Ile

610 615 620

Val Val Ser Lys Leu Lys Ala Asn Leu Met Cys Lys Thr Asp Ile Lys

625 630 635 640

Cys Arg Leu Ala Lys Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Thr

645 650 655

His Glu Val Val Phe Ala Phe Val Met Asp Glu His Ala Arg Gly Thr

660 665 670

Leu Arg Phe Ile Lys Leu Phe Thr Glu Leu Ser Phe Thr Ser Phe Gln

675 680 685

Gly Leu Met Val Ala Ile Leu Tyr Cys Phe Val Asn Asn Glu Val Gln

690 695 700

Met Glu Phe Arg Arg Ser Trp Glu Arg Trp Arg Leu Lys His Leu His

705 710 715 720

Ile Gln Arg Asp Ser Ser Met Lys Pro Leu Lys Cys Pro Thr Ser Ser

725 730 735

Leu Thr Ser Gly Gly Thr Val Gly Ser Ser Val Tyr Ala Ala Ser Cys

740 745 750

Gln Ala Ser Cys Ser

755

<210> 49

<211> 126

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: N-terminal domain of mature

feline glucagon-like peptide receptor-1 (GLP1R-N)

<400> 49

Arg Pro Leu Pro Ala Ser Gly Gly Ala Thr Val Ser Leu Ser Glu Thr

1 5 10 15

Val Gln Lys Trp Arg Glu Tyr Arg His Gln Cys Gln Arg Phe Leu Thr

20 25 30

Glu Ala Pro Pro Pro Ala Thr Gly Leu Phe Cys Asn Arg Thr Phe Asp

35 40 45

Glu Tyr Ala Cys Trp Pro Asp Gly Leu Pro Gly Ser Phe Val Asn Val

50 55 60

Ser Cys Pro Trp Tyr Leu Pro Trp Ala Ser Ser Val Leu Gln Gly His

65 70 75 80

Val Tyr Arg Phe Cys Thr Ala Glu Gly Leu Trp Leu Arg Gln Asp Asn

85 90 95

Ser Ser Leu Pro Trp Arg Asn Leu Ser Glu Cys Glu Glu Ser Lys Arg

100 105 110

Gly Glu Arg Ser Ser Pro Glu Glu Gln Leu Leu Ser Phe Ser

115 120 125

<210> 50

<211> 392

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssFeGLP1R-N_huFc_ PolyHis

<400> 50

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro

1 5 10 15

Gly Ser Thr Gly Arg Pro Leu Pro Ala Ser Gly Gly Ala Thr Val Ser

20 25 30

Leu Ser Glu Thr Val Gln Lys Trp Arg Glu Tyr Arg His Gln Cys Gln

35 40 45

Arg Phe Leu Thr Glu Ala Pro Pro Pro Ala Thr Gly Leu Phe Cys Asn

50 55 60

Arg Thr Phe Asp Glu Tyr Ala Cys Trp Pro Asp Gly Leu Pro Gly Ser

65 70 75 80

Phe Val Asn Val Ser Cys Pro Trp Tyr Leu Pro Trp Ala Ser Ser Val

85 90 95

Leu Gln Gly His Val Tyr Arg Phe Cys Thr Ala Glu Gly Leu Trp Leu

100 105 110

Arg Gln Asp Asn Ser Ser Leu Pro Trp Arg Asn Leu Ser Glu Cys Glu

115 120 125

Glu Ser Lys Arg Gly Glu Arg Ser Ser Pro Glu Glu Gln Leu Leu Ser

130 135 140

Phe Ser Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp

145 150 155 160

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

165 170 175

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

180 185 190

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

195 200 205

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

210 215 220

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

225 230 235 240

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

245 250 255

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

260 265 270

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

275 280 285

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

290 295 300

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

305 310 315 320

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

325 330 335

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

340 345 350

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

355 360 365

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

370 375 380

Gly Lys His His His His His

385 390

<210> 51

<211> 156

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssFeGLP1R-N_PolyHis

<400> 51

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro

1 5 10 15

Gly Ser Thr Gly Arg Pro Leu Pro Ala Ser Gly Gly Ala Thr Val Ser

20 25 30

Leu Ser Glu Thr Val Gln Lys Trp Arg Glu Tyr Arg His Gln Cys Gln

35 40 45

Arg Phe Leu Thr Glu Ala Pro Pro Pro Ala Thr Gly Leu Phe Cys Asn

50 55 60

Arg Thr Phe Asp Glu Tyr Ala Cys Trp Pro Asp Gly Leu Pro Gly Ser

65 70 75 80

Phe Val Asn Val Ser Cys Pro Trp Tyr Leu Pro Trp Ala Ser Ser Val

85 90 95

Leu Gln Gly His Val Tyr Arg Phe Cys Thr Ala Glu Gly Leu Trp Leu

100 105 110

Arg Gln Asp Asn Ser Ser Leu Pro Trp Arg Asn Leu Ser Glu Cys Glu

115 120 125

Glu Ser Lys Arg Gly Glu Arg Ser Ser Pro Glu Glu Gln Leu Leu Ser

130 135 140

Phe Ser Gly Gly Gly Ser His His His His His

145 150 155

<210> 52

<211> 326

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/Gluc-3G_IV_WTfeIgG2

<400> 52

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

50 55 60

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

65 70 75 80

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

85 90 95

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

100 105 110

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

115 120 125

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

130 135 140

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

145 150 155 160

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

165 170 175

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

180 185 190

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

195 200 205

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

210 215 220

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

225 230 235 240

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

245 250 255

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

260 265 270

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys Gly Gly Gly

275 280 285

Gly Ser Gly Gly Gly Gly His Ser Gln Gly Thr Phe Thr Ser Asp Tyr

290 295 300

Ser Lys Tyr Leu Asp Ser Arg Arg Ala Gln Asp Phe Val Gln Trp Leu

305 310 315 320

Met Asn Thr Gly Gly Gly

325

<210> 53

<211> 326

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Gluc/GLP1-2G_V_ WTfeIgG2

<400> 53

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser

1 5 10 15

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Gly Gly Gly

20 25 30

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

35 40 45

Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro

50 55 60

Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe

65 70 75 80

Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val

85 90 95

Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile

100 105 110

Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro

115 120 125

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro

130 135 140

Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val

145 150 155 160

Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala

165 170 175

Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln

180 185 190

Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly

195 200 205

Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro

210 215 220

Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp

225 230 235 240

Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp

245 250 255

Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His

260 265 270

Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys Gly Gly

275 280 285

Gly Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp

290 295 300

Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp

305 310 315 320

Leu Val Lys Gly Gly Gly

325

<210> 54

<211> 324

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/Glu-4G_IV_ VARcaIgGD

<400> 54

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys Pro Val Pro

50 55 60

Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu

85 90 95

Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

100 105 110

Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

130 135 140

Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu

145 150 155 160

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

165 170 175

Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser

180 185 190

Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

195 200 205

Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser

210 215 220

Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

225 230 235 240

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp

245 250 255

Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

260 265 270

Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly

275 280 285

Gly Gly Gly His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr

290 295 300

Leu Asp Ser Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr

305 310 315 320

Gly Gly Gly Gly

<210> 55

<211> 323

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Gluc/GLP1-3G_V_ VARcaIgGD

<400> 55

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser

1 5 10 15

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys Pro Val Pro

50 55 60

Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu

85 90 95

Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

100 105 110

Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

130 135 140

Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu

145 150 155 160

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

165 170 175

Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser

180 185 190

Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

195 200 205

Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser

210 215 220

Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

225 230 235 240

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp

245 250 255

Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

260 265 270

Asp Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly

275 280 285

Gly Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

290 295 300

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

305 310 315 320

Gly Gly Gly

<210> 56

<211> 319

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/Gluc-4G_IV_

VAReqIgGD

<400> 56

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ser

275 280 285

Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser Arg Arg

290 295 300

Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Gly Gly Gly Gly

305 310 315

<210> 57

<211> 318

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Gluc/GLP1-3G_V_ VAReqIgG2

<400> 57

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser

1 5 10 15

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala

275 280 285

Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala

290 295 300

Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

305 310 315

<210> 58

<211> 321

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/Glu-4G_IV_ huIgG4

<400> 58

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

50 55 60

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

65 70 75 80

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

85 90 95

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

100 105 110

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

115 120 125

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

130 135 140

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

145 150 155 160

Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

165 170 175

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys

180 185 190

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

195 200 205

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

210 215 220

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

225 230 235 240

Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

245 250 255

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

260 265 270

Leu Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly

275 280 285

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser

290 295 300

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Gly Gly Gly

305 310 315 320

Gly

<210> 59

<211> 321

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Gluc/GLP1-3G_V_huIgG4

<400> 59

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser

1 5 10 15

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Gly Gly Gly

20 25 30

Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Ser

35 40 45

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

50 55 60

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

65 70 75 80

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

85 90 95

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

100 105 110

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

115 120 125

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

130 135 140

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

145 150 155 160

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

165 170 175

Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

180 185 190

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

195 200 205

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

210 215 220

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

225 230 235 240

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

260 265 270

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala

275 280 285

Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala

290 295 300

Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly Gly Gly

305 310 315 320

Gly

<210> 60

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-A-Fc variant,

C1q -, Protein A +, I(21)T,

Q(207)H

<400> 60

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu His Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 61

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-C-Fc variant,

C1q+, Protein A+, I(21)T

<400> 61

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 62

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-D-Fc variant,

C1q -, Protein A +, I(21)T,

Q(207)H

<400> 62

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 63

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Wild type equine IgG1-Fc, Protein A+, C1q+

<400> 63

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu

35 40 45

Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro

85 90 95

Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile

130 135 140

Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 64

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Horse IgG2-Fc wild type, Protein A -, C1q -

<400> 64

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser

20 25 30

Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu

35 40 45

Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro

85 90 95

Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val

130 135 140

Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile

195 200 205

Ser Glu Ser Leu Gly Lys

210

<210> 65

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Wild type horse IgG3-Fc, Protein A+, C1q+

<400> 65

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser

20 25 30

His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu

35 40 45

Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn

65 70 75 80

Gly Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr

145 150 155 160

Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 66

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type equine IgG4-Fc, Protein A+, C1q+

<400> 66

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 67

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Horse IgG5-Fc wild type, Protein A -, C1q -

<400> 67

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly

20 25 30

His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser His Ser Pro Gly Lys

210

<210> 68

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Horse IgG6-Fc wild type, Protein A -, C1q -

<400> 68

Gly Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Ala His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Gln

100 105 110

Val Tyr Ile Leu Ala Pro His Pro Asp Glu Val Thr Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val

130 135 140

Glu Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile

195 200 205

Thr Asn Phe Pro Gly Lys

210

<210> 69

<211> 214

<212> Protein

<213> Unknown origin

<220>

<223> Wild type equine IgG7-Fc, Protein A+, C1q+

<400> 69

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 70

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG1-Fc variant,

Protein A +, C1q -, K(87)S

<400> 70

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu

35 40 45

Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Asn Asn Gln Ala Leu Pro Gln Pro

85 90 95

Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile

130 135 140

Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 71

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG2-Fc variant,

C1q -, Protein A+, F(203)Y

<400> 71

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser

20 25 30

Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu

35 40 45

Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro

85 90 95

Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val

130 135 140

Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Gly Glu Ser Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile

195 200 205

Ser Glu Ser Leu Gly Lys

210

<210> 72

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG2-Fc variant,

C1q -, Protein A+, A(15)T,

F(203)Y

<400> 72

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser

20 25 30

Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu

35 40 45

Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro

85 90 95

Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val

130 135 140

Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile

195 200 205

Ser Glu Ser Leu Gly Lys

210

<210> 73

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG3-Fc variant,

Protein A +, C1q -, K(87)S

<400> 73

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser

20 25 30

His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu

35 40 45

Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn

65 70 75 80

Gly Lys Lys Phe Lys Cys Ser Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr

145 150 155 160

Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 74

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG4-Fc variant,

Protein A +, C1q -, K(87)S

<400> 74

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Asn Asn Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 75

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG5-Fc variant,

C1q -, Protein A +, V(199)L,

E(200)H

<400> 75

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly

20 25 30

His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser His Ser Pro Gly Lys

210

<210> 76

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG6-Fc variant,

C1q -, Protein A +, I(199)L,

R(200)H, H(201)N, T(202)H

<400> 76

Gly Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Ala His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Gln

100 105 110

Val Tyr Ile Leu Ala Pro His Pro Asp Glu Val Thr Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val

130 135 140

Glu Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Leu His Asn His Tyr Arg Gln Lys Ser Ile

195 200 205

Thr Asn Phe Pro Gly Lys

210

<210> 77

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Equine IgG7-Fc variant,

Protein A +, C1q -, K(87)S

<400> 77

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr

50 55 60

Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 78

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgB-Fc variant,

Protein A +, C1q -, K(93)R

<400> 78

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 79

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgC-Fc variant,

Protein A -, C1q -, K(93)R

<400> 79

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 80

<211> 237

<212> Protein

<213> Unknown origin

<220>

<223> Alternative feline IgG1a-Fc wild type, Protein A+, C1q+

<400> 80

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 81

<211> 237

<212> Protein

<213> Unknown origin

<220>

<223> Alternative feline IgG1b-Fc wild type, Protein A+, C1q+

<400> 81

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 82

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Feline IgG1a-Fc variant,

Protein A+, C1q -, P(198)A

<400> 82

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 83

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Feline IgG1b-Fc variant,

Protein A+, C1q -, P(198)A

<400> 83

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 84

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: Canine IgG-C-Fc variant,

C1q - , K(93)R , Protein A

+, I(21)T, V(23)L, T(24)I

<400> 84

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 85

<211> 31

<212> Protein

<213> Unknown origin

<220>

<223> Wild type GLP1 (7-37)

<400> 85

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Ala Gly

20 25 30

<210> 86

<211> 29

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-S8 (7-35)

<400> 86

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

20 25

<210> 87

<211> 29

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8 (7-35)

<400> 87

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

20 25

<210> 88

<211> 1

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 1G extension

<400> 88

Gly

1

<210> 89

<211> 2

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 2G extension

<400> 89

Gly Gly

1

<210> 90

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 3G extension

<400> 90

Gly Gly Gly

1

<210> 91

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 4G extension

<400> 91

Gly Gly Gly Gly

1

<210> 92

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 5G extension

<400> 92

Gly Gly Gly Gly Gly

15

<210> 93

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 6G extension

<400> 93

Gly Gly Gly Gly Gly Gly

15

<210> 94

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 7G extension

<400> 94

Gly Gly Gly Gly Gly Gly Gly

15

<210> 95

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: 8G extension

<400> 95

Gly Gly Gly Gly Gly Gly Gly Gly

15

<210> 96

<211> 305

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8_I_WTfeIgG2

<400> 96

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly

65 70 75 80

Glu Gly Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val

85 90 95

Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr

100 105 110

Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn

115 120 125

Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys

130 135 140

Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

145 150 155 160

Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys

165 170 175

Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile

180 185 190

Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro

195 200 205

Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu

210 215 220

Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr

225 230 235 240

Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu

245 250 255

Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg

260 265 270

Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu

275 280 285

Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly

290 295 300

Lys

305

<210> 97

<211> 346

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: ssGLP1-G8/GLP1-3G_III_

WTfeIgG2

<400> 97

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr

20 25 30

Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

35 40 45

Gly Ala Gly Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

50 55 60

Gly Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly

65 70 75 80

Glu Gly Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val

85 90 95

Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr

100 105 110

Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn

115 120 125

Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys

130 135 140

Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

145 150 155 160

Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys

165 170 175

Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile

180 185 190

Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro

195 200 205

Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu

210 215 220

Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr

225 230 235 240

Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu

245 250 255

Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg

260 265 270

Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu

275 280 285

Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly

290 295 300

Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala Glu Gly Thr Phe

305 310 315 320

Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe

325 330 335

Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

340 345

<210> 98

<211> 30

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1 variant (7-36)

<400> 98

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Ala

20 25 30

<210> 99

<211> 29

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1 variant (7-35)

<400> 99

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly

20 25

<210> 100

<211> 229

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type equine IgG2-Fc (including hinge region

horse IgG2), Protein A

- , C1q -

<400> 100

Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly

1 5 10 15

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met

20 25 30

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

35 40 45

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

50 55 60

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

65 70 75 80

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

85 90 95

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

100 105 110

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

115 120 125

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

130 135 140

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

145 150 155 160

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

165 170 175

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

180 185 190

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

195 200 205

Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser

210 215 220

Glu Ser Leu Gly Lys

225

<210> 101

<211> 14

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type equine IgG1 hinge region

<400> 101

Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu

1 5 10

<210> 102

<211> 15

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type equine IgG2 hinge region

<400> 102

Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu

1 5 10 15

<210> 103

<211> 318

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLP1-3G_III_

VAReqIgG2

<400> 103

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly

50 55 60

Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met

65 70 75 80

Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp

85 90 95

Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val

100 105 110

His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr

115 120 125

Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly

130 135 140

Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile

145 150 155 160

Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val

165 170 175

Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser

180 185 190

Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu

195 200 205

Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr

210 215 220

Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu

225 230 235 240

Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala

245 250 255

Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser

260 265 270

Glu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly His Ala

275 280 285

Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala

290 295 300

Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

305 310 315

<210> 104

<211> 279

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8_I_VAReqIgG2

<400> 104

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Ala Gly

20 25 30

Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

35 40 45

Ser Ser Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe

50 55 60

Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr

65 70 75 80

Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu

85 90 95

Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr

100 105 110

Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser

115 120 125

Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu

130 135 140

Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln

145 150 155 160

Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro

165 170 175

Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys

180 185 190

Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser

195 200 205

Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser

210 215 220

Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser

225 230 235 240

Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr

245 250 255

Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp

260 265 270

Ile Ser Glu Ser Leu Gly Lys

275

<210> 105

<211> 321

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLP1-2G_III_

VARcaIgGD

<400> 105

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro Glu

50 55 60

Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp

65 70 75 80

Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp

85 90 95

Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly

100 105 110

Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe Asn

115 120 125

Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp

130 135 140

Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro

145 150 155 160

Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln

165 170 175

Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser

180 185 190

Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu

195 200 205

Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys

210 215 220

Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu

225 230 235 240

Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr

245 250 255

Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Asp

260 265 270

Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly

275 280 285

Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu

290 295 300

Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly

305 310 315 320

Gly

<210> 106

<211> 321

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence: GLP1-G8/GLP1-2G_III_

VARcaIgGD

<400> 106

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

35 40 45

Pro Lys Glu Ser Thr Ser Lys Cys Ile Ser Pro Cys Pro Val Pro Glu

50 55 60

Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp

65 70 75 80

Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp

85 90 95

Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly

100 105 110

Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe Asn

115 120 125

Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp

130 135 140

Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro

145 150 155 160

Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln

165 170 175

Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser

180 185 190

Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu

195 200 205

Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys

210 215 220

Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu

225 230 235 240

Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr

245 250 255

Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Asp

260 265 270

Leu Ser Leu Ser His Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly

275 280 285

Gly Gly His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu

290 295 300

Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly

305 310 315 320

Gly

<210> 107

<211> 237

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type canine IgG-B-Fc with hinge region, Protein A+,

C1q+, CD16+

<400> 107

Pro Lys Arg Glu Asn Gly Arg Val Pro Arg Pro Pro Asp Cys Pro Lys

1 5 10 15

Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr

35 40 45

Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser

50 55 60

Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn

100 105 110

Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg

115 120 125

Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu

130 135 140

Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe

145 150 155 160

Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

165 170 175

Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly

180 185 190

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

195 200 205

Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn

210 215 220

His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

225 230 235

<210> 108

<211> 235

<212> Protein

<213> Unknown origin

<220>

<223> Wild type canine IgG-C-Fc with hinge region, Protein A,

C1q+, CD16+

<400> 108

Ala Lys Glu Cys Glu Cys Lys Cys Asn Cys Asn Asn Cys Pro Cys Pro

1 5 10 15

Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys

20 25 30

Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys Val

35 40 45

Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp Phe

50 55 60

Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu Glu

65 70 75 80

Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His

85 90 95

Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn Lys

100 105 110

Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly Gln

115 120 125

Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu Met

130 135 140

Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe Pro

145 150 155 160

Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu

165 170 175

Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr

180 185 190

Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly

195 200 205

Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr

210 215 220

Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

225 230 235

<210> 109

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-A-Fc variant, Heterodimeric chain 3, T(138)W

<400> 109

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Trp Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 110

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-A-Fc variant, Heterodimeric chain 4, T(138)S,

L(140)A,

Y(181)T

<400> 110

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Ser Cys Ala Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 111

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Heterodimeric chain 3, T(137)W

<400> 111

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Trp Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 112

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Heterodimeric chain 4, T(137)S,

L(139)A,

Y(180)T

<400> 112

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Ser Cys Ala Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 113

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Heterodimeric chain 3, T(137)W

<400> 113

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Trp Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 114

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Heterodimeric chain 4, T(137)S,

L(139)A,

Y(180)T

<400> 114

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Ser Cys Ala Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 115

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-D-Fc variant, Heterodimeric chain 3, T(138)W

<400> 115

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Trp Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 116

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-D-Fc variant, Heterodimeric chain 4, T(138)S,

L(140)A,

Y(181)T

<400> 116

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Ser Cys Ala Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Thr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 117

<211> 237

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type feline IgG1a-Fc, Protein A+, C1q+

<400> 117

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 118

<211> 237

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type feline IgG1b-Fc, Protein A+, C1q+

<400> 118

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 119

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG2-Fc variant, Heterodimeric chain 1, T(154)W

<400> 119

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 120

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG2-Fc variant, Heterodimeric chain 2, T(154)S,

L(156)A,

Y(197)T

<400> 120

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Thr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 121

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1a-Fc variant, Heterodimeric chain 1, T(154)W

<400> 121

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 122

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1a-Fc variant, Heterodimeric chain 2, T(154)S,

L(156)A,

Y(197)T

<400> 122

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Thr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 123

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1b-Fc variant, Heterodimeric chain 1, T(154)W

<400> 123

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 124

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1b-Fc variant, Heterodimeric chain 2, T(154)S,

L(156)A,

Y(197)T

<400> 124

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Thr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 125

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG2-Fc variant, with feline hinge region

IgG1

<400> 125

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 126

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG2-Fc variant with modified hinge

region, K(16)P

<400> 126

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Pro

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 127

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1a-Fc variant with modified hinge

region, K(16)P

<400> 127

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Pro

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 128

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1b-Fc variant with modified hinge

region, K(16)P

<400> 128

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Pro

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 129

<211> 244

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type equine IgG2-Fc with hinge region, Protein A,

C1q

<400> 129

Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 130

<211> 244

<212> Protein

<213> Artificial sequence

<220>

<223> Equine IgG2-Fc variant with modified hinge

region, Protein A, C1q,

Q(20)P

<400> 130

Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 131

<211> 244

<212> Protein

<213> Artificial sequence

<220>

<223> Equine IgG2-Fc variant with modified hinge

region, Protein A, C1q,

C(3)S

<400> 131

Pro Pro Ser Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 132

<211> 244

<212> Protein

<213> Artificial sequence

<220>

<223> Equine IgG2-Fc variant with modified hinge

region, Protein A, C1q,

C(3)S, Q(20)P

<400> 132

Pro Pro Ser Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 133

<211> 244

<212> Protein

<213> Artificial sequence

<220>

<223> Equine IgG2-Fc variant with modified hinge

region, Protein A +, C1q, A(45)T,

F(233)Y

<400> 133

Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 134

<211> 244

<212> Protein

<213> Artificial sequence

<220>

<223> Equine IgG2-Fc variant with modified hinge

region, Protein A+, C1q,

Q(20)P, A(45)T, F(233)Y

<400> 134

Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 135

<211> 244

<212> Protein

<213> Artificial sequence

<220>

<223> Equine IgG2-Fc variant with modified hinge

region, Protein A+, C1q,

C(3)S, Q(20)P, A(45)T, F(233)Y

<400> 135

Pro Pro Ser Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly

20 25 30

Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile

35 40 45

Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln

50 55 60

Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His

65 70 75 80

Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg

85 90 95

Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys

100 105 110

Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser

115 120 125

Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr

130 135 140

Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val

145 150 155 160

Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp

165 170 175

Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro

180 185 190

Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser

195 200 205

Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val

210 215 220

Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu

225 230 235 240

Ser Leu Gly Lys

<210> 136

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223>Feline IgG1a-Fc variant, Protein A+, C1q, P(198)A

<400> 136

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 137

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Feline IgG1b-Fc variant, Protein A+, C1q, P(198)A

<400> 137

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 138

<211> 30

<212> Protein

<213> Unknown origin

<220>

<223> Wild-type equine IgG2 hinge region

<400> 138

Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val

1 5 10 15

Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu

20 25 30

<210> 139

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Protein A+, C1q+, CD16, M(5)P

<400> 139

Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 140

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Protein A+, C1q+, CD16, P(39)R

<400> 140

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 141

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Protein A+, C1q+, CD16, D(38)G

<400> 141

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Gly Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 142

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Protein A+, C1q+, CD16, K(97)I

<400> 142

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Ile Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 143

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-B-Fc, Protein A+, C1q+, CD16, A(98)G

<400> 143

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 144

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-B-Fc variant, Protein A+, C1q+, CD16, D(38)G,

K(97)I, A(98)G

<400> 144

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Gly Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 145

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-B-Fc, Protein A+, C1q, CD16, D(38)G,

K(93)R, K(97)I, A(98)G

<400> 145

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Gly Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 146

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223>Canine IgG-B-Fc variant, Protein A+, C1q+, CD16, M(5)P,

P(39)R

<400> 146

Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 147

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-B-Fc, Protein A+, C1q, CD16, M(5)P,

P(39)R,

K(93)R

<400> 147

Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 148

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Protein A+, C1q+, CD16, L(5)P

<400> 148

Pro Gly Cys Gly Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 149

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-C-Fc, Protein A+, C1q+, CD16, P(39)R

<400> 149

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Arg Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 150

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Protein A+, C1q+, CD16, D(38)G

<400> 150

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Gly Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 151

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Protein A+, C1q+, CD16, K(97)I

<400> 151

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Ile Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 152

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-C-Fc, Protein A+, C1q+, CD16, A(98)G

<400> 152

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Gly Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 153

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-C-Fc, Protein A+, C1q, CD16+, K(93)R

<400> 153

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 154

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Protein A+, C1q+, CD16, D(38)G,

K(97)I, A(98)G

<400> 154

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Gly Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 155

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Variant canine IgG-C-Fc, Protein A+, C1q, CD16, D(38)G,

K(93)R, K(97)I, A(98)G

<400> 155

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Gly Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 156

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Protein A+, C1q+, CD16, L(5)P,

P(39)R

<400> 156

Pro Gly Cys Gly Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Arg Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 157

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Canine IgG-C-Fc variant, Protein A+, C1q. CD16, M(5)P,

P(39)R,

K(93)R

<400> 157

Pro Gly Cys Gly Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Arg Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 158

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-A-Fc, N(68)X

<220>

<221> other signs

<222> (68)..(68)

<223> X = any amino acid except N

<400> 158

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Xaa Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 159

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-A-Fc, G(69)P

<400> 159

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 160

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-A-Fc, T(70)X

<220>

<221> other signs

<222> (70)..(70)

<223> X = any amino acid except T or S

<400> 160

Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu

50 55 60

Gln Gln Phe Asn Gly Xaa Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe

130 135 140

Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

145 150 155 160

Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 161

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-B-Fc, N(68)X

<220>

<221> other signs

<222> (68)..(68)

<223> X = any amino acid except N

<400> 161

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Xaa Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 162

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-B-Fc, G(69)P

<400> 162

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 163

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-B-Fc, T(70)X

<220>

<221> other signs

<222> (70)..(70)

<223> X = any amino acid except T or S

<400> 163

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Glu Gln Phe Asn Gly Xaa Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu

115 120 125

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

130 135 140

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 164

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-C-Fc, N(68)X

<220>

<221> other signs

<222> (68)..(68)

<223> X = any amino acid except N

<400> 164

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Xaa Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 165

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-C-Fc, G(69)P

<400> 165

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 166

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-C-Fc, T(70)X

<220>

<221> other signs

<222> (70)..(70)

<223> X = any amino acid except T or S

<400> 166

Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys

20 25 30

Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu

50 55 60

Glu Gln Ser Asn Gly Xaa Tyr Arg Val Val Ser Val Leu Pro Ile Gly

65 70 75 80

His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn

85 90 95

Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly

100 105 110

Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu

115 120 125

Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe

130 135 140

Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

145 150 155 160

Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

165 170 175

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

180 185 190

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

195 200 205

Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 167

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-D-Fc, N(68)X

<220>

<221> other signs

<222> (68)..(68)

<223> X = any amino acid except N

<400> 167

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Xaa Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 168

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-D-Fc, S(69)P

<400> 168

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 169

<211> 221

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of canine IgG-D-Fc, T(70)X

<220>

<221> other signs

<222> (70)..(70)

<223> X = any amino acid except T or S

<400> 169

Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

1 5 10 15

Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys

20 25 30

Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp

35 40 45

Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu

50 55 60

Gln Gln Phe Asn Ser Xaa Tyr Arg Val Val Ser Val Leu Pro Ile Glu

65 70 75 80

His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His

85 90 95

Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

100 105 110

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu

115 120 125

Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe

130 135 140

Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu

145 150 155 160

Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly

165 170 175

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

180 185 190

Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn

195 200 205

His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys

210 215 220

<210> 170

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG1a-Fc, N(85)X

<220>

<221> other signs

<222> (85)..(85)

<223> X = any amino acid except N

<400> 170

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Xaa Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 171

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG1a-Fc, S(86)P

<400> 171

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 172

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG1a-Fc, T(87)X

<220>

<221> other signs

<222> (87)..(87)

<223> X = any amino acid except T or S

<400> 172

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Xaa Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 173

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG1b-Fc, N(85)X

<220>

<221> other signs

<222> (85)..(85)

<223> X = any amino acid except N

<400> 173

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Xaa Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 174

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG1b-Fc, S(86)P

<400> 174

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 175

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG1b-Fc, T(87)X

<220>

<221> other signs

<222> (87)..(87)

<223> X = any amino acid except T or S

<400> 175

Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys

1 5 10 15

Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Xaa Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe

145 150 155 160

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 176

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG2-Fc, N(85)X

<220>

<221> other signs

<222> (85)..(85)

<223> X= any amino acid except N

<400> 176

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Xaa Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 177

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG2-Fc, S(86)P

<400> 177

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Pro Thr Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 178

<211> 237

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of feline IgG2-Fc, T(87)X

<220>

<221> other signs

<222> (87)..(87)

<223> X = any amino acid except T or S

<400> 178

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys

1 5 10 15

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

20 25 30

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

35 40 45

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

50 55 60

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

65 70 75 80

Glu Glu Gln Phe Asn Ser Xaa Tyr Arg Val Val Ser Val Leu Pro Ile

85 90 95

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

100 105 110

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

115 120 125

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

130 135 140

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

145 150 155 160

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

165 170 175

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

180 185 190

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

195 200 205

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

210 215 220

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

225 230 235

<210> 179

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG1-Fc, N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 179

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu

35 40 45

Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Xaa Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro

85 90 95

Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile

130 135 140

Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 180

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG1-Fc, S(63)P

<400> 180

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu

35 40 45

Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro

85 90 95

Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile

130 135 140

Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 181

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG1-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 181

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu

35 40 45

Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro

85 90 95

Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile

130 135 140

Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 182

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG2-Fc, N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 182

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser

20 25 30

Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu

35 40 45

Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Xaa Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro

85 90 95

Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val

130 135 140

Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile

195 200 205

Ser Glu Ser Leu Gly Lys

210

<210> 183

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG2-Fc, S(63)P

<400> 183

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser

20 25 30

Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu

35 40 45

Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro

85 90 95

Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val

130 135 140

Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile

195 200 205

Ser Glu Ser Leu Gly Lys

210

<210> 184

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG2-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 184

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser

20 25 30

Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu

35 40 45

Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro

85 90 95

Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val

130 135 140

Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile

195 200 205

Ser Glu Ser Leu Gly Lys

210

<210> 185

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG3-Fc, N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 185

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser

20 25 30

His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu

35 40 45

Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Xaa Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn

65 70 75 80

Gly Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr

145 150 155 160

Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 186

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG3-Fc, S(63)P

<400> 186

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser

20 25 30

His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu

35 40 45

Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn

65 70 75 80

Gly Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr

145 150 155 160

Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 187

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG3-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 187

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser

20 25 30

His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu

35 40 45

Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn

65 70 75 80

Gly Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr

145 150 155 160

Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile

195 200 205

Ser Lys Asn Pro Gly Lys

210

<210> 188

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG4-Fc, N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 188

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Xaa Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 189

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG4-Fc, S(63)P

<400> 189

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 190

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG4-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 190

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 191

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG5-Fc,N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 191

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly

20 25 30

His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Xaa Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser His Ser Pro Gly Lys

210

<210> 192

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG5-Fc, S(63)P

<400> 192

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly

20 25 30

His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser His Ser Pro Gly Lys

210

<210> 193

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG5-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 193

Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly

20 25 30

His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val

130 135 140

Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys

180 185 190

Gly Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val

195 200 205

Ser His Ser Pro Gly Lys

210

<210> 194

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG6-Fc, N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 194

Gly Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Ala His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Xaa Ser Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Gln

100 105 110

Val Tyr Ile Leu Ala Pro His Pro Asp Glu Val Thr Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val

130 135 140

Glu Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile

195 200 205

Thr Asn Phe Pro Gly Lys

210

<210> 195

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG6-Fc, S(63)P

<400> 195

Gly Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Ala His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Gln

100 105 110

Val Tyr Ile Leu Ala Pro His Pro Asp Glu Val Thr Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val

130 135 140

Glu Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile

195 200 205

Thr Asn Phe Pro Gly Lys

210

<210> 196

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG6-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 196

Gly Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

20 25 30

Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Ala His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro

85 90 95

Val Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Gln

100 105 110

Val Tyr Ile Leu Ala Pro His Pro Asp Glu Val Thr Lys Asn Thr Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val

130 135 140

Glu Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys

180 185 190

Val Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile

195 200 205

Thr Asn Phe Pro Gly Lys

210

<210> 197

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG7-Fc, N(62)X

<220>

<221> other signs

<222> (62)..(62)

<223> X = any amino acid except N

<400> 197

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Xaa Ser Thr

50 55 60

Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 198

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of horse IgG7-Fc, S(63)P

<400> 198

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Pro Thr

50 55 60

Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<210> 199

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Aglycosylated variant of equine IgG7-Fc, T(64)X

<220>

<221> other signs

<222> (64)..(64)

<223> X = any amino acid except T or S

<400> 199

Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu

1 5 10 15

Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly

20 25 30

His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

35 40 45

Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Xaa

50 55 60

Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser

65 70 75 80

Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro

85 90 95

Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln

100 105 110

Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val

115 120 125

Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile

130 135 140

Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr

145 150 155 160

Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

165 170 175

Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys

180 185 190

Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val

195 200 205

Ser Lys Ser Pro Gly Lys

210

<---

Claims (75)

1. An IgG-Fc polypeptide component having reduced binding affinity to C1q and CD16 and/or reduced antibody-dependent cellular cytotoxicity (ADCC), comprising a variant of a canine IgG-B-Fc polypeptide containing an amino acid sequence at least 90% identical to the amino acid sequence SEQ ID NO: 78, SEQ ID NO: 145 or SEQ ID NO: 147; and wherein an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 78, SEQ ID NO: 145 or SEQ ID NO: 147 contains arginine at a position corresponding to position 93 in SEQ ID NO: 2. 2. The IgG-Fc polypeptide component of claim 1, wherein the variant IgG-Fc polypeptide contains at least one amino acid modification in the hinge region relative to a wild-type feline or equine IgG-Fc polypeptide, wherein the variant IgG-Fc polypeptide has increased production in recombinant system and/or increased formation of disulfide bonds in the hinge region relative to the wild-type IgG-Fc polypeptide, as determined by SDS-PAGE under reducing and/or non-reducing conditions. 3. An IgG-Fc polypeptide component according to claim 1 or 2, wherein the IgG-Fc polypeptide variant contains: an amino acid substitution at a position corresponding to position 5 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 38 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 39 in SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 97 in SEQ ID NO: 2, and/or an amino acid substitution at a position corresponding to position 98 in SEQ ID NO: 2. 4. An IgG-Fc polypeptide component according to any one of claims 1-3, wherein the IgG-Fc polypeptide variant contains: an amino acid substitution at position 5 in SEQ ID NO: 2, an amino acid substitution at position 38 in SEQ ID NO: 2, an amino acid substitution at position 39 in SEQ ID NO: 2, an amino acid substitution at position 97 in SEQ ID NO: 2 and/or amino acid substitution at position 98 in SEQ ID NO: 2. 5. An IgG-Fc polypeptide component according to any one of claims 1 to 4, wherein the IgG-Fc polypeptide variant contains: proline at a position corresponding to position 5 in SEQ ID NO: 2, glycine at a position corresponding to position 38 in SEQ ID NO: 2, arginine at a position corresponding to position 39 in SEQ ID NO: 2, isoleucine at a position corresponding to position 97 in SEQ ID NO: 2, and/or glycine at a position corresponding to position 98 in SEQ ID NO: 2. 6. An IgG-Fc polypeptide component according to any one of claims 1 to 5, wherein the IgG-Fc polypeptide variant contains: proline at position 5 in SEQ ID NO: 2, glycine at position 38 in SEQ ID NO: 2, arginine at position 39 in SEQ ID NO: 2, isoleucine at position 97 in SEQ ID NO: 2 and/or glycine at position 98 from SEQ ID NO: 2. 7. The IgG-Fc polypeptide component according to any one of claims 1 to 6, wherein the variant IgG-Fc polypeptide contains the amino acid sequence of SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146 or SEQ ID NO: 147. 8. A polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising an IgG-Fc polypeptide component according to claim 1 and a glucagon-like peptide-1 (GLP-1) polypeptide; where the polypeptide includes from N- to C-terminus: N-[GLP1]–L1–Fc–C or N-[GLP1]–L1–Fc–L2–[GLP1]; where [GLP1] includes an amino acid sequence selected from the group consisting of SEQ ID NO: 26, 85, 86, 98, 99; where L1 and L2 are linkers, each independently being a flexible linker containing one or more amino acids. 9. A polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising an IgG-Fc polypeptide component according to claim 1 and a glucagon polypeptide (Gluc); where the polypeptide includes from N-terminus to C-terminus: N-[Gluc]–L1–Fc–C or N-[Gluc]–L1–Fc–L2–[Gluc]; where [Gluc] includes an amino acid sequence selected from the group consisting of SEQ 21, 92, 93, 94, 95; where L1 and L2 are linkers, each independently being a flexible linker containing one or more amino acids. 10. A polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 8 or 9, wherein the polypeptide is glycosylated. 11. A polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 8 or 9, wherein the polypeptide is aglycosylated. 12. A continuous polypeptide for the treatment of a metabolic disease, containing a variant of the polypeptide IgG-Fc component according to claim 1, containing: serine at the position corresponding to position 137 of SEQ ID NO: 2; alanine at the position corresponding to position 139 of SEQ ID NO: 2; threonine at the position corresponding to position 180 of SEQ ID NO: 2; wherein the polypeptide IgG-Fc component is glycosylated or aglycosylated; and wherein the IgG-Fc polypeptide component is linked to a glucagon-like peptide-1 (GLP1) polypeptide by a linker, with a functional GLP-1 moiety at the N-terminus of the fusion construct followed by the linker, and an immunoglobulin at the C-terminus. 13. A continuous polypeptide for the treatment of diabetes, obesity and metabolic disease associated with diabetes or obesity, comprising a variant of the IgG-Fc polypeptide component according to claim 1, comprising: serine at the position corresponding to position 137 of SEQ ID NO: 2; alanine at the position corresponding to position 139 of SEQ ID NO: 2; threonine at the position corresponding to position 180 of SEQ ID NO: 2; wherein the polypeptide IgG-Fc component is glycosylated or aglycosylated; and wherein the IgG-Fc polypeptide component is linked to the glucagon polypeptide through a linker, with a functional Gluc moiety at the N-terminus of the fusion construct, followed by the linker, and an immunoglobulin at the C-terminus. 14. A heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising a continuous polypeptide according to claim 8 and a continuous polypeptide according to claim 12, wherein the two polypeptides are not the same. 15. A heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising a continuous polypeptide according to claim 9 and a continuous polypeptide according to claim 13, wherein the two polypeptides are not the same. 16. The continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 8, wherein the GLP1 polypeptide is a wild-type GLP1 Polypeptide, optionally comprising the amino acid sequence of SEQ ID NO: 85. 17. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 8, wherein the GLP1 polypeptide is a variant of the GLP1 polypeptide. 18. A continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 8, wherein the GLP1 polypeptide comprises the amino acid sequence of SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 98 or SEQ ID NO: 99. 19. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 9, wherein the glucagon polypeptide is a wild-type glucagon polypeptide, optionally comprising the amino acid sequence of SEQ ID NO: 21. 20. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 19, wherein the glucagon polypeptide is a variant of the glucagon polypeptide. 21. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 18, wherein said polypeptide is an antibody, fusion antibody or fusion polypeptide. 22. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 18, wherein at least one amino acid modification or substitution comprises an amino acid substitution with an amino acid derivative. 23. An isolated nucleic acid encoding a continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, according to claim 8. 24. An isolated nucleic acid encoding a continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, according to claim 9. 25. A host cell for expressing a continuous polypeptide, comprising a nucleic acid encoding a continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 8, embedded in an expression vector, where the host cell is not an embryonic cell person. 26. A host cell for expressing a continuous polypeptide, comprising a nucleic acid encoding a continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 9, embedded in an expression vector, where the host cell is not an embryonic cell person. 27. A method of producing a polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising culturing a host cell expressing the continuous polypeptide of claim 8 and isolating the continuous polypeptide, wherein the host cell is not a human embryonic cell. 28. A method of producing a polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising culturing a host cell expressing the continuous polypeptide of claim 9 and isolating the continuous polypeptide, wherein the host cell is not a human embryonic cell. 29. A pharmaceutical composition for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, containing a continuous polypeptide according to claim 8 or 9 and a pharmaceutically acceptable carrier. 30. A method of delivering a continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity to a subject, comprising administering the continuous polypeptide of claim 8 or 9 parenterally. 31. A method of delivering a continuous polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity to a subject, comprising administering the continuous polypeptide of claim 8 or 9 by the intramuscular route, intraperitoneal route, intracerebrospinal route, subcutaneous route, intraarterial route, intra-articular route , intrathecal route or inhalation route. 32. A method of treating diabetes, obesity, and a metabolic disease associated with diabetes or obesity in a subject using the continuous polypeptide of claim 8 or 9, wherein the subject is canine. 33. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 19, wherein the glucagon polypeptide is a variant of the glucagon polypeptide. 34. The continuous polypeptide for the treatment of diabetes, obesity, and a metabolic disease associated with diabetes or obesity according to claim 19, wherein the polypeptide is an antibody, a fusion antibody, or a fusion polypeptide. 35. The continuous polypeptide for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 19, wherein the at least one amino acid modification or substitution comprises replacing the amino acid with an amino acid derivative. 36. The heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the GLP1 polypeptide is a wild-type GLP1 polypeptide optionally comprising the amino acid sequence of SEQ ID NO: 85. 37. The heterodimeric protein for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the GLP1 polypeptide is a variant of the GLP1 polypeptide. 38. The heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 15, wherein the glucagon polypeptide is a variant of the glucagon polypeptide. 39. The heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the GLP1 polypeptide comprises the amino acid sequence of SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 98 or SEQ ID NO: 99. 40. The heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the GLP1 polypeptide comprises the amino acid sequence of SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 98 or SEQ ID NO: 99. 41. The heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 15, wherein the glucagon polypeptide is a wild-type glucagon polypeptide optionally comprising the amino acid sequence of SEQ ID NO: 21. 42. The heterodimeric protein for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the GLP1 polypeptide is a variant of the GLP1 polypeptide. 43. The heterodimeric protein for treating diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 15, wherein the glucagon polypeptide is a variant of the glucagon polypeptide. 44. The heterodimeric protein for treating diabetes, obesity, and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the polypeptide comprises an antibody, a fusion antibody, or a fusion polypeptide. 45. The heterodimeric protein for treating diabetes, obesity, and a metabolic disease associated with diabetes or obesity according to claim 14, wherein the at least one amino acid modification or substitution comprises replacing the amino acid with an amino acid derivative. 46. The heterodimeric protein for treating diabetes, obesity, and a metabolic disease associated with diabetes or obesity according to claim 15, wherein the polypeptide comprises an antibody, a fusion antibody, or a fusion polypeptide. 47. The heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 15, wherein the at least one amino acid modification or substitution comprises replacing the amino acid with an amino acid derivative. 48. An isolated nucleic acid encoding a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, according to claim 14. 49. A host cell for expressing a heterodimeric protein, comprising a nucleic acid encoding a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 14, embedded in an expression vector, where the host cell is not an embryonic cell person. 50. A method of producing a polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising culturing a host cell expressing the heterodimeric protein of claim 14, wherein the host cell is not a human embryonic cell. 51. An isolated nucleic acid encoding a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, according to claim 15. 52. A host cell for expressing a heterodimeric protein, comprising a nucleic acid encoding a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity according to claim 15, embedded in an expression vector, where the host cell is not an embryonic cell person. 53. A method of producing a polypeptide for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising culturing a host cell expressing the heterodimeric protein of claim 15, wherein the host cell is not a human embryonic cell. 54. A pharmaceutical composition for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, comprising the polypeptide of claim 14 and a pharmaceutically acceptable carrier. 55. A pharmaceutical composition for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity, containing the heterodimeric protein according to claim 15 and a pharmaceutically acceptable carrier. 56. A method of delivering a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity to a subject, comprising parenteral administration of the heterodimeric protein according to claim 14. 57. A method of delivering a heterodimer protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity to a subject, comprising administering the heterodimer protein according to claim 14 by the intramuscular route, the intraperitoneal route, the intracerebral route, the subcutaneous route, the intra-arterial route, the intrasynovial route, the intrathecal route by or inhalation route. 58. A method of treating diabetes, obesity, and a metabolic disease associated with diabetes or obesity in a subject using the heterodimeric protein of claim 14, wherein the subject is canine. 59. A method of delivering a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity to a subject, comprising parenteral administration of the heterodimeric protein according to claim 15. 60. A method of delivering a heterodimeric protein for the treatment of diabetes, obesity and a metabolic disease associated with diabetes or obesity to a subject, comprising administering the heterodimeric protein according to claim 15 by the intramuscular route, the intraperitoneal route, the intracerebral route, the subcutaneous route, the intra-arterial route, the intrasynovial route, the intrathecal route by or inhalation route. 61. A method of treating diabetes, obesity, and a metabolic disease associated with diabetes or obesity in a subject using the heterodimeric protein of claim 15, wherein the subject is canine.

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