Antisense modulation of liver glycogen phosphorylase expression

• US 6,043,091 A
• Filed: 07/19/1999
• Issued: 03/28/2000
• Est. Priority Date: 07/19/1999
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Monia, Brett P., Cowsert, Lex M.
• Primary Examiner(s): Elliott, George C.
• Assistant Examiner(s): SCHMIDT, MARY M
• Application Number:
  US09/357,071
• Time in Patent Office: 253 Days
• Field of Search: 435/6, 435/91.31, 435/91.1, 435/375, 435/366, 536/23.1, 536/23.2, 536/24.3, 536/24.5, 514/44
• US Class Current: 435/375
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 9/1051 Hexosyltransferases (2.4.1)
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of liver glycogen phosphorylase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding liver glycogen phosphorylase. Methods of using these compounds for modulation of liver glycogen phosphorylase expression and for treatment of diseases associated with expression of liver glycogen phosphorylase are provided.

Claims

1. An antisense compound 8 to 30 nucleobases in length targeted to a coding region from nucleobases 172-2433, a 5'"'"'-untranslated region, a start codon or a 3'"'"'-untranslated region of a nucleic acid encoding human liver glycogen phosphorylase, wherein said antisense compound specifically hybridizes with and inhibits the expression of human liver glycogen phosphorylase.

2. The antisense compound of claim 1 which is an antisense oligonucleotide.

4. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

5. The antisense compound of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.

6. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

7. The antisense compound of claim 6 wherein the modified sugar moiety is a 2'"'"'-O-methoxyethyl sugar moiety.

8. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

9. The antisense compound of claim 8 wherein the modified nucleobase is a 5-methylcytosine.

10. the antisense compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

11. A method of inhibiting the expression of human liver glycogen phosphorlyase in human cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 1 so that expression of human liver glycogen phosphorylase is inhibited.

3. An antisense compound up to 30 nucleobases in length comprising at least an 8-nucleobase portion of SEQ ID NO:

9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, or 47 which inhibits the expression of human liver glycogen phosphorlyase.

12. The antisense compound of claim 3 which is an antisense oligonucleotide.

13. The antisense compound of claim 12 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

14. The antisense compound of claim 13 wherein the modified internucleoside linkage is a phosphorothioate linkage.

15. The antisense compound of claim 12 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

16. The antisense compound of claim 15 wherein the modified sugar moiety is a 2'"'"'-O-methoxyethyl sugar moiety.

17. The antisense compound of claim 12 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

18. The antisense compound of claim 17 wherein the modified nucleobase is a 5-methylcytosine.

19. The antisense compound of claim 12 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

20. A method of inhibiting the expression of human liver glycogen phosphorylase in human cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 3 so that expression of human liver glycogen phosphorylase is inhibited.