Claims
- 1. An enzymatic nucleic acid molecule which specifically cleaves RNA derived from hepatitis C virus (HCV), wherein the binding arms of said enzymatic nucleic acid molecule comprises sequences complementary to any of substrate sequences defined as Seq. ID Nos. 1-4554, 4556-4640, and 4683-4797.
- 2. An enzymatic nucleic acid molecule which specifically cleaves RNA derived from hepatitis C virus (HCV), wherein said enzymatic nucleic acid molecule comprises sequences defined as Seq. ID Nos. 4798-9352, 9354-9442, and 9485-9636.
- 3. The enzymatic nucleic acid molecule of claim 1, wherein said enzymatic nucleic acid molecule is selected from the group consisting of Hammerhead, Inozyme, G-cleaver, DNAzyme, Amberzyme, and Zinzyme motifs.
- 4. The enzymatic nucleic acid molecule of claim 3, wherein said Inozyme enzymatic nucleic acid molecule comprises a stem II region of length greater than or equal to 2 base pairs.
- 5. The enzymatic nucleic acid molecule of claim 1, wherein said enzymatic nucleic acid comprises between 12 and 100 bases complementary to said RNA derived from HCV.
- 6. The enzymatic nucleic acid molecule of claim 1, wherein said enzymatic nucleic acid comprises between 14 and 24 bases complementary to said RNA derived from HCV.
- 7. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of claim 1 or claim 2, in a pharmaceutically acceptable carrier.
- 8. A mammalian cell including an enzymatic nucleic acid molecule of claim 1 or claim 2.
- 9. The mammalian cell of claim 8, wherein said mammalian cell is a human cell.
- 10. An expression vector comprising nucleic acid sequence encoding at least one enzymatic nucleic acid molecule of claim 1, in a manner which allows expression of that enzymatic nucleic acid molecule.
- 11. A mammalian cell including an expression vector of claim 10.
- 12. The mammalian cell of claim 10, wherein said mammalian cell is a human cell.
- 13. A method for treatment of cirrhosis, liver failure or hepatocellular carcinoma comprising the step of administering to a patient the enzymatic nucleic acid molecule of any of claims 1 or 2 under conditions suitable for said treatment.
- 14. A method for treatment of cirrhosis, liver failure and/or hepatocellular carcinoma comprising the step of administering to a patient the expression vector of claim 10 under conditions suitable for said treatment.
- 15. A method of treatment of a patient having a condition associated with HCV infection, comprising contacting cells of said patient with the nucleic acid molecule of any of claims 1 or 2, and further comprising the use of one or more drug therapies under conditions suitable for said treatment.
- 16. A method for inhibiting HCV replication in a mammalian cell comprising the step of administering to said cell the enzymatic nucleic acid molecule of any of claims 1 or 2 under conditions suitable for said inhibition.
- 17. A method of cleaving a separate RNA molecule comprising, contacting the enzymatic nucleic acid molecule of any of claims 1 or 2 with said separate RNA molecule under conditions suitable for the cleavage of said separate RNA molecule.
- 18. The method of claim 17, wherein said cleavage is carried out in the presence of a divalent cation.
- 19. The method of claim 18, wherein said divalent cation is Mg2+.
- 20. The enzymatic nucleic acid molecule of claim 1 or claim 2, wherein said nucleic acid is chemically synthesized.
- 21. The expression vector of claim 10, wherein said vector comprises:
a. a transcription initiation region; b. a transcription termination region; c. a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.
- 22. The expression vector of claim 10, wherein said vector comprises:
a. a transcription initiation region; b. a transcription termination region; c. an open reading frame; d. a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3′-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.
- 23. The expression vector of claim 10, wherein said vector comprises:
a. a transcription initiation region; b. a transcription termination region; c. an intron; d. a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.
- 24. The expression vector of claim 10, wherein said vector comprises:
a. a transcription initiation region; b. a transcription termination region; c. an intron; d. an open reading frame; e. a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3′-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said intron, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.
- 25. The enzymatic nucleic acid molecule of claim 1 or claim 2, wherein said enzymatic nucleic acid comprises at least one 2′-sugar modification.
- 26. The enzymatic nucleic acid molecule of claim 1 or claim 2, wherein said enzymatic nucleic acid comprises at least one nucleic acid base modification.
- 27. The enzymatic nucleic acid molecule of claim 1 or claim 2, wherein said enzymatic nucleic acid comprises at least one phosphate modification.
- 28. The method of claim 15, wherein said drug therapies is type I interferon.
- 29. The method of claim 28, wherein said type I interferon and the enzymatic nucleic acid molecule is administered simultaneously.
- 30. The method of claim 28, wherein said type I interferon and enzymatic nucleic acid molecule is administered separately.
- 31. The method of claim 28, wherein said type I interferon is interferon alpha.
- 32. The method of claim 28, wherein said type I interferon is interferon beta.
- 33. The method of claim 28, wherein said type I interferon is consensus interferon.
- 34. The method of claim 28, wherein said type I interferon is polyethylene glycol interferon.
- 35. The method of claim 28, wherein said type I interferon is polyethylene glycol interferon alpha 2a.
- 36. The method of claim 28, wherein said type I interferon is polyethylene glycol interferon alpha 2b.
- 37. The method of claim 28, wherein said type I interferon is polyethylene glycol consensus interferon.
- 38. A pharmaceutical composition comprising type I interferon and the enzymatic nucleic acid molecule of claim 1 or claim 2, in a pharmaceutically acceptable carrier.
Parent Case Info
[0001] This patent application is a continuation-in-part of Blatt et al., U.S. Ser. No. (not yet assigned), filed Jul. 7, 2000, which is a continuation-in-part of Blatt et al., 09/504,321, filed Feb. 15, 2000, which is a continuation-in-part of Blatt et al., U.S. Ser. No. 09/274,553, filed Mar. 23, 1999, which is a continuation-in-part of Blatt et al., U.S. Ser. No. 09/257,608, filed Feb. 24, 1999 (abandoned), which claims priority from Blatt et al, U.S. Ser. No. 60/100,842, filed Sep. 18, 1998, and McSwiggen et al., U.S. Ser. No. 60/083,217 filed Apr. 27, 1998, all of these earlier applications are entitled “ENZYMATIC NUCLEIC ACID TREATMENT OF DISEASES OR CONDITIONS RELATED TO HEPATITIS C VIRUS INFECTION”. Each of these applications are hereby incorporated by reference herein in their entirety including the drawings.