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CA2286396A1 - Oligonucleotides for enhanced bioavailability - Google Patents

Oligonucleotides for enhanced bioavailability Download PDF

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Publication number
CA2286396A1
CA2286396A1 CA002286396A CA2286396A CA2286396A1 CA 2286396 A1 CA2286396 A1 CA 2286396A1 CA 002286396 A CA002286396 A CA 002286396A CA 2286396 A CA2286396 A CA 2286396A CA 2286396 A1 CA2286396 A1 CA 2286396A1
Authority
CA
Canada
Prior art keywords
cancelled
modification
pharmaceutical composition
oligonucleotide
alkoxyalkoxy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002286396A
Other languages
French (fr)
Other versions
CA2286396C (en
Inventor
Nicholas M. Dean
C. Frank Bennet
Brett P. Monia
Kenneth Draper
Kevin P. Anderson
Brenda F. Baker
David J. Ecker
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ionis Pharmaceuticals Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2286396A1 publication Critical patent/CA2286396A1/en
Application granted granted Critical
Publication of CA2286396C publication Critical patent/CA2286396C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Plant Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)

Abstract

The present invention provides compositions and methods for the alimentary delivery of oligonucleotides in an animal, including a human. Modifications to the oligonucleotide which enhance uptake following alimentary delivery are provided.

Claims (33)

1. An oligonucleotide which, during or after administration into the alimentary canal, has enhanced bioavailability compared to a phosphorothioate oligodeoxynucleotide of substantially the same sequence, wherein said oligonucleotide comprises at least one heteroatomic backbone modification and a 2'-alkoxyalkoxy modification.
2. (Cancelled).
3. (Cancelled).
4. (Cancelled).
5. (Cancelled).
6, (Cancelled).
7. (Cancelled).
8. The oligonucleotide of claim 1 wherein said 2'-alkoxyalkoxy modification is a 2'-methoxyethoxy modification.
9. (Cancelled).
10. A pharmaceutical composition comprising the oligonucleotide of claim 1.
11. The pharmaceutical composition of claim 10 which comprises a colloidal dispersion system.
12. The pharmaceutical composition of claim 10 which comprises at least one penetration enhancer.
13. The pharmaceutical composition of claim 12 wherein the penetration enhancer comprises a bile salt or a fatty acid.
14. The pharmaceutical composition of claim 13 wherein the bile salt is CDCA.
15. The pharmaceutical composition of claim 13 wherein the fatty acid is sodium caprate or sodium laurate.
16. The pharmaceutical composition of claim 13 which comprises both one or more bile salts and one or more fatty acids.
17. A pharmaceutical composition comprising an oligonucleotide having at least one 2'-alkoxyalkoxy modification and at least one 5-methylcytidine.
18. The pharmaceutical composition of claim 17 wherein said 2'-alkoxyalkoxy modification is a 2'-methoxyethoxy modification.
19. (Cancelled).
20. (Cancelled).
21. (Cancelled).
22. (Cancelled).
23. (Cancelled).
24. (Cancelled).
25. (Cancelled).
26. (Cancelled).
27. A method of modulating expression of a target nucleic acid comprising administering into the alimentary canal an effective amount of an oligonucleotide that has at least one nitrogenous heteroatomic backbone modification, hybridizes to said target nucleic acid, and modulates the expression thereof.
28. The method of claim 27 wherein said administration into the alimentary canal is oral, rectal, endoscopic, sublingual or buccal administration.

-41/b-
29. The method of claim 27 wherein said heteroatomic backbone modification is a methylene(methylimino) modification.
30. The method of claim 27 wherein said administration into the alimentary canal is oral, rectal, endoscopic, sublingual or buccal administration.
31. The method of claim 27 wherein said oligonucleotide has a 2'-O-alkyl or 2'-alkoxyalkoxy modification.
32. The method of claim 31 wherein said 2'-O-alkyl modification is a 2'-O-methyl or 2'-O-propyl modification.
33. The method of claim 31 wherein said 2'-alkoxyalkoxy modification is a 2'-methoxyethoxy modification.
CA2286396A 1997-04-30 1998-04-30 Oligonucleotides for enhanced bioavailability Expired - Fee Related CA2286396C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US84715197A 1997-04-30 1997-04-30
US08/847,151 1997-04-30
PCT/US1998/008798 WO1998049348A1 (en) 1997-04-30 1998-04-30 Oligonucleotides for enhanced bioavailability

Publications (2)

Publication Number Publication Date
CA2286396A1 true CA2286396A1 (en) 1998-11-05
CA2286396C CA2286396C (en) 2010-07-06

Family

ID=25299899

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2286396A Expired - Fee Related CA2286396C (en) 1997-04-30 1998-04-30 Oligonucleotides for enhanced bioavailability

Country Status (6)

Country Link
EP (1) EP0979309A4 (en)
JP (1) JP2000514095A (en)
KR (1) KR20010020370A (en)
AU (1) AU738352B2 (en)
CA (1) CA2286396C (en)
WO (1) WO1998049348A1 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2294988C (en) * 1997-07-01 2015-11-24 Isis Pharmaceuticals Inc. Compositions and methods for the delivery of oligonucleotides via the alimentary canal
CA2333087C (en) * 1998-05-21 2014-07-08 Isis Pharmaceuticals Inc. Compositions and methods for the pulmonary delivery of nucleic acids
ES2628744T3 (en) 1998-05-22 2017-08-03 Ottawa Hospital Research Institute Methods and products to induce immunity in mucous membranes
WO2000050050A1 (en) * 1999-02-23 2000-08-31 Isis Pharmaceuticals, Inc. Multiparticulate formulation
US6168950B1 (en) * 1999-07-23 2001-01-02 Isis Pharmaceuticals, Inc. Antisense modulation of MEKK1 expression
AU7070800A (en) * 1999-08-27 2001-03-26 Chiron Corporation Chimeric antisense oligonucleotides and cell transfecting formulations thereof
US6677445B1 (en) 1999-08-27 2004-01-13 Chiron Corporation Chimeric antisense oligonucleotides and cell transfecting formulations thereof
CN100344646C (en) 2001-07-10 2007-10-24 奥林格斯技术有限公司 Oligonucleotide-containing pharmacological compositions and their use
US20030124196A1 (en) * 2001-08-22 2003-07-03 Susan Weinbach Pulsatile release compositions and methods for enhanced intestinal drug absorption
AU2009315898B2 (en) 2008-11-13 2015-07-23 Nogra Pharma Limited Antisense compositions and methods of making and using same

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5214135A (en) * 1991-08-30 1993-05-25 Chemgenes Corporation N-protected-2'-O-methyl-ribonucleosides and N-protected 2'-O-methyl-3'-cyanoethyl-N-,N-diisopropyl phosphoramidite ribonucleosides
US5948898A (en) * 1992-03-16 1999-09-07 Isis Pharmaceuticals, Inc. Methoxyethoxy oligonucleotides for modulation of protein kinase C expression
US5681747A (en) * 1992-03-16 1997-10-28 Isis Pharmaceuticals, Inc. Nucleic acid sequences encoding protein kinase C and antisense inhibition of expression thereof
ATE177430T1 (en) * 1993-05-12 1999-03-15 Novartis Erfind Verwalt Gmbh NUCLEOSIDES AND OLIGONUCLEOTIDES WITH 2'-ETHER GROUPS
US5591721A (en) * 1994-10-25 1997-01-07 Hybridon, Inc. Method of down-regulating gene expression
US6096720A (en) * 1995-08-01 2000-08-01 Novartis Ag Liposomal oligonucleotide compositions

Also Published As

Publication number Publication date
AU738352B2 (en) 2001-09-13
EP0979309A4 (en) 2000-10-18
JP2000514095A (en) 2000-10-24
KR20010020370A (en) 2001-03-15
AU7272398A (en) 1998-11-24
CA2286396C (en) 2010-07-06
EP0979309A1 (en) 2000-02-16
WO1998049348A1 (en) 1998-11-05

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Effective date: 20140430