Antisense inhibition of src-c expression

• US 6,656,732 B1
• Filed: 05/18/2001
• Issued: 12/02/2003
• Est. Priority Date: 05/18/2001
• Status: Active Grant

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Bennett, C. Frank, Watt, Andrew T.
• Primary Examiner(s): Lacourciere, Karen
• Application Number:
  US09/860,473
• Time in Patent Office: 928 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 435/325, 435/375, 536/23.1, 536/23.2, 536/24.3, 536/24.31, 536/24.33, 536/24.5, 514/44
• US Class Current: 435/375
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy
• 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 src-c. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding src-c. Methods of using these compounds for modulation of src-c expression and for treatment of diseases associated with expression of src-c are provided.

Claims

1. A compound 8 to 50 nucleobases in length targeted to, nucleobases 179 through 219, nucleobases 249 through 295, nucleobases 317 through 336, nucleobases 349 through 397, nucleobases 427 through 446, nucleobases 469 through 495, nucleobases 499 through 526, nucleobases 589 through 608, nucleobases 658 through 706, nucleobases 711 through 730, nucleobases 747 through 767, nucleobases 809 through 834, nucleobases 857 through 892, nucleobases 1050 through 1091, nucleobases 1184 through 1227, nucleobases 1372 through 1391, or nucleobases 1486 through 1530 of a coding region of a nucleic acid molecule encoding src-c of SEQ ID NO:

3, or nucleobases 1592 through 1611 of a stop codon region of a nucleic acid molecule encoding src-c of SEQ ID NO;

3, wherein said compound specifically hybridizes with one of said regions and inhibits the expression of src-c.

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

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

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

6. The compound of claim 5 wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

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

8. The compound of claim 7 wherein the modified nucleobase is a 5-methylcytosine.

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

10. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

11. The composition of claim 10 further comprising a colloidal dispersion system.

12. The composition of claim 10 wherein the compound is an antisense oligonucleotide.

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

13. A compound up to 50 nucleobases in length comprising at least an 8-nucleobase portion of SEQ ID NO:

29, 35, 44, 45, 46, 48, 53, 54, 56, 57, 58, 60, 61, 62, 63, 64, 65, 67, 69, 70, 71, 72, 73, 76, 77, 79, 80, 81, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 52, 68, 78, 108, 110, 113, 118, 120, 121, 124, 125, 128, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 143, 145, 146, 147, 148, 151, 155, 157, 158, 163, 164, 167, 168 or 169 which inhibits the expression of src-c.

14. The compound of claim 13 which is an antisense oligonucleotide.

15. The compound of claim 14 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

16. The compound of claim 15 wherein the modified internucleoside linkage is a phosphorothioate linkage.

17. The compound of claim 14 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

18. The compound of claim 17 wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

19. The compound of claim 14 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

20. The compound of claim 19 wherein the modified nucleobase is a 5-methylcytosine.

21. The compound of claim 14 wherein the antisense oligonucleotide is chimeric oligonucleotide.

22. A composition comprising the compound of claim and a pharmacologically acceptable carrier or diluent.

23. The composition of claim 22 further comprising a colloidal dispersion system.

24. The composition of claim 22 wherein the antisense compound is an antisense oligonucleotide.

25. A compound consisting of SEQ ID NO:

30.