Antisense modulation of smad7expression

• US 20030049662A1
• Filed: 07/17/2002
• Published: 03/13/2003
• Est. Priority Date: 01/19/2000
• Status: Abandoned Application

• Current Assignee: Brett P. Monia, Lex M. Cowsert
• Original Assignee: Brett P. Monia, Lex M. Cowsert
• Inventors: Monia, Brett P., Cowsert, Lex M.
• Application Number:
  US10/181,603
• Publication Number:
  US 20030049662A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 Smad7. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Smad7. Methods of using these compounds for modulation of Smad7 expression and for treatment of diseases associated with expression of Smad7 are provided.

Claims

1. An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding Smad7, wherein said antisense compound specifically hybridizes with and inhibits the expression of Smad7.

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

3. The antisense compound of claim 2 wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO:

10, 12, 14, 16, 19, 24, 25, 30, 33, 35, 38, 40, 11, 18, 20, 22, 27, 31, 36, 37, 39, 41 or 42.

4. The antisense compound of claim 2 wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO:

10, 16, 24, 25, 30 or 40.

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

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

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

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

-O-methoxyethyl sugar moiety.

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

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

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

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

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

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

15. A method of inhibiting the expression of Smad7 in cells or tissues comprising contacting said cells or tissues with the antisense compound of claim 1 so that expression of Smad7 is inhibited.

16. A method of treating a human having a disease or condition associated with Smad7 comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of claim 1 so that expression of Smad7 is inhibited.

17. The method of claim 16 wherein the disease or condition is a developmental disorder.

18. The method of claim 16 wherein the disease or condition is a cardiovascular disorder.

19. The method of claim 16 wherein the disease or condition is a hyperproliferative disorder.

20. The method of claim 16 wherein the disease or condition is a wound healing disorder.