Enzymatic RNA molecule targeted against Hepatitis C virus

• US 5,610,054 A
• Filed: 01/13/1994
• Issued: 03/11/1997
• Est. Priority Date: 05/14/1992
• Status: Expired due to Fees

• Current Assignee: Ribozyme Pharmaceuticals, Inc. (Alnylam Pharmaceuticals Incorporated)
• Original Assignee: Ribozyme Pharmaceuticals, Inc. (Alnylam Pharmaceuticals Incorporated)
• Inventors: Draper, Kenneth G.
• Primary Examiner(s): LeGuyader, John L.
• Application Number:
  US08/182,968
• Time in Patent Office: 1,153 Days
• Field of Search: 514/44, 435/69.1, 435/6, 435/91.31, 435/172.3, 435/320.1, 435/240.2, 530/350, 536/23.1, 536/23.2, 536/24.5
• US Class Current: 435/363
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/121 Hammerhead
• CPC Class Codes: C12N 2310/122 Hairpin
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2310/3531 Hydrogen
• CPC Class Codes: C12N 2310/3533 Halogen
• CPC Class Codes: C12N 2310/3535 Nitrogen
• CPC Class Codes: C12N 2770/24222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/24243 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12Q 1/701 : Specific hybridization probes
• CPC Class Codes: C12Q 1/707 : non-A, non-B Hepatitis, excluding hepatitis D

Abstract

An enzymatic RNA molecule which specifically cleaves RNA of a hepatitis C virus.

Claims

1. An enzymatic RNA molecule which is active to specifically cleave RNA of hepatitis C virus (HCV).

2. The enzymatic RNA molecule of claim 1 which specifically cleaves RNA of HCV in the 5'"'"'non-translated region.

3. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is in a hammerhead motif.

4. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is in a hairpin, hepatitis Delta virus, group I intron, or RNaseP RNA motif.

5. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule specifically cleaves the RNA sequence comprising any of SEQ. ID. NOS. 1-8, and wherein said enzymatic RNA molecule is in a hepatitis Delta virus configuration.

6. The enzymatic RNA molecule of claim 1 which specifically cleaves RNA of HCV in the RNA encoding the core (c) region.

7. The enzymatic RNA molecule of claim 1 which specifically cleaves RNA of HCV in the RNA encoding the proteases NS3 or NS2NS3.

8. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule specifically cleaves the RNA sequence comprising any of SEQ. ID. NOS. 001-506, and wherein said enzymatic RNA molecule is in a hepatitis Delta virus configuration.

9. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule specifically cleaves the RNA sequence comprising any of SEQ. ID. NOS. 001-506, and wherein said enzymatic RNA molecule is in a hammerhead configuration.

10. The enzymatic RNA molecule of any of claims 1-5 and 6-9, wherein said enzymatic RNA molecule comprises at least one sugar modification.

11. The enzymatic RNA molecule of any of claims 1-5 and 6-9, wherein said enzymatic RNA molecule comprises at least one phosphate backbone modification.

12. The enzymatic RNA molecule of claim 10, wherein said sugar modification is a 2'"'"'-O-methyl group.

13. The enzymatic RNA molecule of claim 11, wherein said phosphate modification is a phosphorothioate group.

14. An expression vector including a nucleic acid encoding the enzymatic RNA molecule of may of claims 1-5, and 6-9, in a manner which allows expression of said enzymatic RNA molecule within a mammalian cell in vitro.

15. A mammalian cell including the enzymatic RNA molecule of any of claims 1-5, and 6-9, in vitro.

16. The cell of claim 15, wherein said cell is a human cell.