Antisense modulation of interleukin 12 p35 subunit expression

• US 6,399,379 B1
• Filed: 05/07/2001
• Issued: 06/04/2002
• Est. Priority Date: 09/29/1992
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Freier, Susan M., Baker, Brenda F.
• Primary Examiner(s): LeGuyader, John L.
• Assistant Examiner(s): SCHMIDT, MARY M
• Application Number:
  US09/851,520
• Time in Patent Office: 393 Days
• Field of Search: 435/6, 435/325, 435/366, 435/375, 435/91.1, 536/23.1, 536/24.5, 536/25.3, 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 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• 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 Interleukin 12 p35 subunit. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interleukin 12 p35 subunit. Methods of using these compounds for modulation of Interleukin 12 p35 subunit expression and for treatment of diseases associated with expression of Interleukin 12 p35 subunit are provided.

Claims

1. A compound 8 to 50 nucleobases in length targeted to nucleobases 1 through 9 or nucleobases 61 through 85 of a 5′

-untranslated region, nucleobases 148 through 167, nucleobases 183 through 201, nucleobases 230 through 249, nucleobases 255 through 274, nucleobases 282 through 304, nucleobases 332 through 351, nucleobases 356 through 409, nucleobases 435 through 521, nucleobases 542 through 572, nucleobases 587 through 705, nucleobases 727 through 756, nucleobases 790 through 823, or nucleobases 828 through 847 of a coding region, a stop codon region, nucleobases 877 through 896, nucleobases 908 through 958, nucleobases 987 through 1006, nucleobases 1035 through 1060, nucleobases 1066 through 1092, nucleobases 1099 through 1177, nucleobases 1194 through 1231, or nucleobases 1284 through 1303 of a 3′

-untranslated region of a nucleic acid molecule encoding human lnterleukin 12 p35 subunit (SEQ ID NO;

     3), or nucleobases 1597-1698 of a coding region of a nucleic acid molecule encoding Interleukin 12 p35 subunit (SEQ ID NO;

     10), wherein said compound specifically hybridizes with one of said regions and inhibits the expression of human Interleukin 12 p35 subunit.

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

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

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

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

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

-O-methoxyethyl sugar moiety.

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

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

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

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

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

13. The composition of claim 11, wherein the compound is an antisense oligonucleotide.

14. A method of inhibiting the expression of human Interleukin 12 p35 subunit in cells or tissues comprising contacting said cells or tissues in vitro with the compound of claim 1 so that expression of human Interleukin 12 p35 subunit is inhibited.

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

11, 13, 14, 16, 17, 20, 21, 22, 23, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 42, 44, 45, 46, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 66, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 82, 85, 87 or 88 which inhibits the expression of Interleukin 12 p35 subunit.

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

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

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

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

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

-O-methoxyethyl sugar moiety.

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

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

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

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.

26. A method of inhibiting the expression of interleukin 12 p35 subunit in cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 3 so that expression of inhibiting the expression of Interleukin 12 p35 subunit is inhibited.