HRP20220888T1 - Ne-humane životinje koje imaju konstruirani lokus imunoglobulinskog lamba lakog lanca - Google Patents
Ne-humane životinje koje imaju konstruirani lokus imunoglobulinskog lamba lakog lanca Download PDFInfo
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- HRP20220888T1 HRP20220888T1 HRP20220888TT HRP20220888T HRP20220888T1 HR P20220888 T1 HRP20220888 T1 HR P20220888T1 HR P20220888T T HRP20220888T T HR P20220888TT HR P20220888 T HRP20220888 T HR P20220888T HR P20220888 T1 HRP20220888 T1 HR P20220888T1
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- 108060003951 Immunoglobulin Proteins 0.000 title claims 17
- 102000018358 immunoglobulin Human genes 0.000 title claims 17
- 241001465754 Metazoa Species 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 claims 53
- 241001529936 Murinae Species 0.000 claims 13
- 238000003780 insertion Methods 0.000 claims 10
- 230000037431 insertion Effects 0.000 claims 10
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 9
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 9
- 102000025171 antigen binding proteins Human genes 0.000 claims 6
- 108091000831 antigen binding proteins Proteins 0.000 claims 6
- 239000003623 enhancer Substances 0.000 claims 5
- 210000004602 germ cell Anatomy 0.000 claims 5
- 230000008707 rearrangement Effects 0.000 claims 5
- 238000000034 method Methods 0.000 claims 4
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims 3
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims 3
- 210000001671 embryonic stem cell Anatomy 0.000 claims 3
- 108020004414 DNA Proteins 0.000 claims 2
- 108091092724 Noncoding DNA Proteins 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 102100029567 Immunoglobulin kappa light chain Human genes 0.000 claims 1
- 101710189008 Immunoglobulin kappa light chain Proteins 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
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- A01K2207/00—Modified animals
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
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- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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Claims (14)
1. Miš čiji genom zametne linije sadrži endogeni lokus imunoglobulinskog λ lakog lanca koji sadrži:
(a) jedan ili više segmenata humanog Vλ gena,
(b) jedan ili više segmenata humanog Jλ gena ,
(c) jedan ili više segmenata humanog Cλ gena, i
(d) mišji Cλ genski segment,
gdje (a) i (b) su sposobni za preraspodjelu kako bi formirali preraspodijeljene gene humane λ varijabilne regije koji su izraženi zajedno s genskim segmentom(ima) konstantne regije od (c) kao λ laki lanci antigen vezujućih proteina, i
gdje (a) i (b) su također sposobni za preraspodjelu da formiraju preraspodijeljene gene humane λ varijabilne regije koji su izraženi zajedno s mišjim Cλ genskim segmentom od (d) kao λ laki lanci antigen vezujućih proteina, i
gdje endogeni lokus imunoglobulinskog λ lakog lanca dalje sadrži: jedan ili više mišjih pojačivača (Eλ) imunoglobulinskog λ lakog lanca, i jedan ili više humanih pojačivača (Eλ) imunoglobulinskog λ lakog lanca.
2. Miš prema patentnom zahtjevu 1, gdje:
(a) endogeni lokus imunoglobulinskog λ lakog lanca sadrži dva mišja Eλs, izborno gdje dva mišja EλS su mišji Eλ i mišji Eλ3-1; ili
(b) endogeni lokus imunoglobulinskog λ lakog lanca sadrži tri humana Eλs.
3. Miš prema patentnom zahtjevu 1, gdje genom zametne linije dodatno sadrži:
(i) endogeni lokus imunoglobulinskog teškog lanca koji sadrži umetanje jednog ili više humanih VH genskih segmenata, jednog ili više humanih DH genskih segmenata, i jednog ili više humanih JH genskih segmenata, pri čemu humani VH, DH i JH genski segmenti su operativno vezani za mišju konstantnu regiju imunoglobulinskog teškog lanca; ili
(ii) endogeni lokus imunoglobulinskog teškog lanca koji sadrži umetanje jednog ili više humanih VH genskih segmenata, jednog ili više humanih DH genskih segmenata, i jednog ili više humanih JH genskih segmenata, pri čemu humani VH, DH i JH genski segmenti su operativno vezani za mišju konstantnu regiju imunoglobulinskog teškog lanca;
i endogeni lokus imunoglobulinskog κ lakog lanca koji sadrži umetanje jednog ili više humanih Vκ genskih segmenata i jednog ili više humanih Jκ genskih segmenata, pri čemu humani Vκ genski segmenti i jedan ili više humanih Jκ genskih segmenata, gdje su humani Vκ genski segmenti i Jκ genski segmenti operativno u vezi s mišjom imunoglobulinskom Cκ regijom.
4. Miš prema patentnom zahtjevu 3, pri čemu:
umetanje jednog ili više humanih VH genskih segmenata, jednog ili više humanih DH genskih segmenata i jednog ili više humanih JH genskih segmenata zamjenjuje mišje VH, DH, i JH genske segmente, izborno gdje umetanje uključuje humanu nekodirajuću DNK koja se prirodno javlja između humanih VH, DH, i JH genskih segmenata, i njihovih kombinacija.
5. Miš prema patentnom zahtjevu 3, pri čemu umetanje jednog ili više humanih Vκ genskih segmenata i jednog ili više humanih Jκ genskih segmenata zamjenjuje mišje Vκ genske segmente i Jκ genske segmente, izborno gdje umetanje uključuje humanu nekodirajuću DNK koja se prirodno javlja između humanih Vκ genskih segmenata i Jκ genskih segmenata, i njihovih kombinacija.
6. Miš prema patentnom zahtjevu 3, gdje mišja konstantna regija teškog lanca imunoglobulina je endogena mišja konstantna regija teškog lanca imunoglobulina.
7. Miš prema patentnom zahtjevu 3, gdje mišja Cκ regija je endogdena mišja Cκ regija.
8. Miš prema patentnom zahtjevu 1, gdje endogeni lokus imunoglobulinskog λ lakog lanca sadrži brisanje endogenih Vλ i Jλ genskih segmenata, u cjelini ili djelomično.
9. Miš prema patentnom zahtjevu 1, gdje mišji Cλ genski segment je mišji Cλ1 genski segment.
10. Miš prema patentnom zahtjevu 3, gdje imunoglobulinski lokus lakog lanca sadrži umetanje proksimalne Vκ duplikacije, u cjelini ili djelomično, lokusa humanog imunoglobulinskog lakog lanca.
11. Miš prema patentnom zahtjevu 3, gdje:
lokus imunoglobulinskog teškog lanca nema endogeni mišji Adam6 gen, opcionalno gdje lokus imunoglobulinskog teškog lanca dodatno sadrži umetanje jedne ili više nukleotidnih sekvenci koje kodiraju jedan ili više mišjih Adam6 polipeptida.
12. Miš prema patentnom zahtjevu 3, pri čemu je miš:
(a) homozigotan na endogenom lokusu imunoglobulinskog teškog lanca;
(b) homozigotan na endogenom lokusu imunoglobulinskog lakog lanca; ili
(c) homozigotan na endogenom lokusu imunoglobulinskog λ lakog lanca.
13. Postupak za stvaranje miša čiji genom zametne linije sadrži konstruirani endogeni lokus imunoglobulinskog λ lakog lanca, postupak sadrži
(a) introdukciju DNK fragmenta u mišje embrionalne matične ćelije, DNK fragment sadrži nukleotidnu sekvencu koja uključuje:
(i) jedan ili više humanih Vλ genskih segmenata,
(ii) jedan ili više humanih Jλ genskih segmenata,
(iii) jedan ili više humanih Cλ genskih segmenata, i
(iv) mišji Cλ genski segment,
gdje su (i) i (ii) sposobni za preraspodjelu da formiraju preraspodijeljene gene humane λ varijabilne regije koje su izražene zajedno s genskim segmentima konstantne regije iz (iii) kao λ laki lanci antigen vezujućih proteina, i gdje (i) i (ii) su također sposobni za preraspodjelu da formiraju preraspodijeljene gene humane λ varijabilne regije koje su izražene zajedno s mišjim Cλ genskim segmentom iz (iv) kao λ laki lanci antigen vezujućih proteina; i
gdje sekvenca nukleotida dalje sadrži jedan ili više pojačivača (Eλ) humanog imunoglobulinskog λ lakog lanca;
(b) dobivanje mišje embrionalne matične ćelije stvorene u (a); i
(c) stvaranje miša upotrebom mišje embrionalne matične ćelije iz (b).
14. Postupak za stvaranje miša čiji genom zametne linije sadrži konstruirani endogeni lokus imunoglobulinskog λ lakog lanca, postupak sadrži:
modificiranje genoma zametne linije miša tako da sadrži konstruirani endogeni lokus imunoglobulinskog λ lakog lanca koji uključuje umetanje:
(a) jednog ili više segmenata humanog Vλ gena,
(b) jednog ili više segmenata humanog Jλ gena,
(c) jednog ili više segmenata humanog Cλ gena, i
(d) mišji Cλ genski segment,
pri čemu (a) i (b) su sposobni za preraspodjelu da formiraju preraspodijeljene gene humane λ varijabilne regije koje su izražene zajedno s genskim segmentom(ima) konstantne regije iz (c) kao λ laki lanci antigen vezujućih proteina, i gdje (a) i (b) su također sposobni za preraspodjelu da formiraju preraspodijeljene gene humane λ varijabilne regije koji su izraženi zajedno s mišjim Cλ genskim segmentom iz (d) kao λ laki lanci antigen vezujućih proteina; i
gdje konstruirani endogeni lokus imunoglobulinskog λ lakog lanca dalje sadrži jedan ili više pojačivača (Eλ) mišjeg imunoglobulinskog λ lakog lanca, i jedan ili više pojačivača (Eλ) humanog imunoglobulinskog λ lakog lanca.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662417845P | 2016-11-04 | 2016-11-04 | |
| US201762567932P | 2017-10-04 | 2017-10-04 | |
| EP20180508.2A EP3766343B1 (en) | 2016-11-04 | 2017-11-03 | Non-human animals having an engineered immunoglobulin lambda light chain locus |
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| Publication Number | Publication Date |
|---|---|
| HRP20220888T1 true HRP20220888T1 (hr) | 2022-10-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20220888TT HRP20220888T1 (hr) | 2016-11-04 | 2017-11-03 | Ne-humane životinje koje imaju konstruirani lokus imunoglobulinskog lamba lakog lanca |
| HRP20201403TT HRP20201403T1 (hr) | 2016-11-04 | 2020-09-03 | Neljudske životinje koje imaju genetski modificiran lokus imunoglobulinskog lambda lakog lanca |
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| Application Number | Title | Priority Date | Filing Date |
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| HRP20201403TT HRP20201403T1 (hr) | 2016-11-04 | 2020-09-03 | Neljudske životinje koje imaju genetski modificiran lokus imunoglobulinskog lambda lakog lanca |
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| US (2) | US10820582B2 (hr) |
| EP (3) | EP4082334A1 (hr) |
| JP (4) | JP6884860B2 (hr) |
| KR (4) | KR102492433B1 (hr) |
| CN (2) | CN114369157A (hr) |
| AU (2) | AU2017391167B2 (hr) |
| BR (1) | BR112019008675A2 (hr) |
| CA (1) | CA3038720A1 (hr) |
| CY (1) | CY1123491T1 (hr) |
| DK (2) | DK3766343T3 (hr) |
| ES (2) | ES2823305T3 (hr) |
| HR (2) | HRP20220888T1 (hr) |
| HU (2) | HUE061980T2 (hr) |
| IL (2) | IL308197A (hr) |
| LT (2) | LT3407709T (hr) |
| MA (2) | MA53935A (hr) |
| MX (2) | MX2019005256A (hr) |
| PL (2) | PL3407709T3 (hr) |
| PT (2) | PT3407709T (hr) |
| RS (2) | RS60886B1 (hr) |
| RU (2) | RU2757665C2 (hr) |
| SG (2) | SG10201913483XA (hr) |
| SI (2) | SI3407709T1 (hr) |
| WO (1) | WO2018128691A1 (hr) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10662256B2 (en) | 2010-07-26 | 2020-05-26 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| CA2806233C (en) | 2010-07-26 | 2021-12-07 | Trianni, Inc. | Transgenic animals and methods of use |
| ME03611B (me) * | 2012-02-01 | 2020-07-20 | Regeneron Pharma | Humanizovani miševi koji eksprimiraju teške lance koji sadrže vl domene |
| WO2017095939A1 (en) | 2015-12-03 | 2017-06-08 | Trianni, Inc. | Enhanced immunoglobulin diversity |
| PL3407709T3 (pl) | 2016-11-04 | 2021-01-11 | Regeneron Pharmaceuticals, Inc. | Zwierzęta inne niż człowiek posiadające zmodyfikowany sposobami inżynierii locus łańcucha lekkiego lambda immunoglobuliny |
| CN112040769B (zh) | 2018-03-24 | 2023-05-16 | 瑞泽恩制药公司 | 用于产生针对肽-mhc复合物的治疗抗体的经过基因修饰的非人动物、制造方法和用途 |
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