Antisense modulation of talin expression

• US 6,372,492 B1
• Filed: 10/30/2000
• Issued: 04/16/2002
• Est. Priority Date: 10/30/2000
• Status: Active Grant

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Bennett, C. Frank, Cowsert, Lex M.
• Primary Examiner(s): Wang, Andrew
• Assistant Examiner(s): SCHMIDT, MARY M
• Application Number:
  US09/702,251
• Time in Patent Office: 533 Days
• Field of Search: 514/44, 435/6, 435/325, 435/366, 435/375, 435/91.1, 536/23.1, 536/24.5, 536/25.3
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 15/113 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 when used in plants C12N15/8218
• 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 Talin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Talin. Methods of using these compounds for modulation of Talin expression and for treatment of diseases associated with expression of Talin are provided.

Claims

1. An antisense compound 16 to 30 nucleobases in length targeted to nucleobases 1 through 19 or nucleobases 73 through 92 of a 5′

-untranslated region, nucleobases 157 through 176, nucleobases 198 through 217, nucleobases 257 through 276, nucleobases 320 through 339, nucleobases 361 through 380, nucleobases 419 through 438, nucleobases 460 through 479, nucleobases 503 through 522, nucleobases 572 through 591, nucleobases 635 through 654, nucleobases 707 through 726, nucleobases 768 through 787, nucleobases 824 through 843, nucleobases 887 through 906, nucleobases 943 through 962, nucleobases 998 through 1017, nucleobases 1057 through 1076, nucleobases 1126 through 1145, nucleobases 1181 through 1200, nucleobases 1236 through 1255, nucleobases 1285 through 1304, nucleobases 1350 through 1369, nucleobases 1421 through 1440, nucleobases 1483 through 1502, nucleobases 1549 through 1568, nucleobases 1602 through 1621, nucleobases 1654 through 1673, nucleobases 1726 through 1745, nucleobases 1781 through 1800, nucleobases 1831 through 1850, nucleobases 1885 through 1904, nucleobases 1948 through 1967, nucleobases 1997 through 2016, nucleobases 2074 through 2093, nucleobases 2146 through 2165, nucleobases 2199 through 2218, nucleobases 2258 through 2277, nucleobases 2314 through 2333, nucleobases 2373 through 2392, nucleobases 2446 through 2465, nucleobases 2515 through 2534, nucleobases 2585 through 2604, nucleobases 2641 through 2660, nucleobases 2712 through 2731, nucleobases 2770 through 2789, nucleobases 2832 through 2851, nucleobases 2906 through 2925, nucleobases 3018 through 3037, nucleobases 3111 through 3130, nucleobases 3195 through 3214, nucleobases 3273 through 3292, nucleobases 3372 through 3391, nucleobases 3441 through 3460, nucleobases 3516 through 3535, nucleobases 3593 through 3612, nucleobases 3709 through 3728, nucleobases 3786 through 3805, nucleobases 3865 through 3884, nucleobases 3950 through 3969, nucleobases 4033 through 4052, nucleobases 4137 through 4156, nucleobases 4219 through 4238, nucleobases 4304 through 4323, nucleobases 4382 through 4401, nucleobases 4550 through 4569, nucleobases 4685 through 4704, nucleobases 4842 through 4861, nucleobases 5067 through 5086, nucleobases 5216 through 5235, nucleobases 6190 through 6209, nucleobases 6681 through 6700, nucleobases 7195 through 7214, or nucleobases 7568 through 7587 of a coding region, nucleobases 7742 through 7761 of a stop codon region or nucleobases 7757 through 7776, nucleobases 7790 through 7809, or nucleobases 8012 through 8031 of a 3′

-untranslated region of a nucleic acid molecule encoding human Talin (SEQ ID NO;

     3),

wherein said antisense compound specifically hybridizes with one of said regions and inhibits the expression of human Talin.

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

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

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

5. The composition of claim 4 further comprising a colloidal dispersion system.

6. The composition of claim 4, wherein the antisense compound is an antisense oligonucleotide.

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

8. The antisense compound of claim 7, wherein the modified internucleoside linkage is a phosphorothioate linkage.

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

10. The antisense compound of claim 9, wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

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

12. The antisense compound of claim 11, wherein the modified nucleobase is a 5-methylcytosine.

13. A method of inhibiting the expression of human Talin 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 Talin is inhibited.

23. A composition comprising the antisense compound of claim 3 and a pharmaceutically acceptable carrier or diluent.

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

25. The composition of claim 23, wherein the antisense compound is an antisense oligonucleotide.

14. An antisense compound up to 30 nucleobases in length comprising at least a 16-nucleobase portion of SEQ ID NO:

11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 42, 43, 45, 46, 47, 48, 50, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 63, 64, 65, 66, 67, 68, 69, 71, 73, 74, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88 or 89 which inhibits the expression of human Talin.

15. The antisense compound of claim 14, which is an antisense oligonucleotide.

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

17. The antisense compound of claim 16, wherein the modified internucleoside linkage is a phosphorothioate linkage.

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

19. The antisense compound of claim 18, wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

20. The antisense compound of claim 15, wherein the antisense oligonucleotide comprises at least one modified nucleobase.

21. The antisense compound of claim 20, wherein the modified nucleobase is a 5-methylcytosine.

22. The antisense compound of claim 15, wherein the antisense oligonucleotide is a chimeric oligonucleotide.

26. A method of inhibiting the expression of human Talin in human cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 14 so that expression of human Talin is inhibited.