Method of treating hepatitis delta virus infection

• US 6,670,342 B2
• Filed: 03/29/2001
• Issued: 12/30/2003
• Est. Priority Date: 03/29/2000
• Status: Expired due to Term

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University), Georgetown University, The University of Georgia Research Foundation, Inc.
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University), Georgetown University, The University of Georgia Research Foundation, Inc.
• Inventors: Tennant, Bud C., Cote, Paul J., Casey, John L., Chu, Chung K., Korba, Brent E., Gerin, John L.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): MCKENZIE, THOMAS C
• Application Number:
  US09/821,278
• Publication Number:
  US 20020160980A1
• Time in Patent Office: 1,006 Days
• Field of Search: 514/86, 514/88, 514/274, 544/309
• US Class Current: 514/86
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/3125 Methylphosphonates
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: G01N 33/5765 Hepatitis delta antigen

Abstract

A method for the treatment for hepatitis delta infection in a host, that includes administering an effective amount of a nucleoside or a nucleoside analog that suppresses the expression of the hepatitis B surface or preS1 antigen in the host 100-fold or more relative to pretreatment values in vivo; or to not more than 1 microgram per milliliter in vivo. In a preferred embodiment, the nucleoside is L-FMAU, or a pharmaceutically acceptable salt or prodrug thereof.

Claims

1. A method for the treatment of hepatitis delta infection comprising administering to a host an effective amount of a β

-L nucleoside of the formula

wherein R is 5-methyl uracil (also referred to as thymine) and R′

is hydrogen, acyl, alkyl, monophosphate, diphosphate, triphosphate, or a phosphate prodrug or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the compound is 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine.

3. The method of claim 2, wherein the compound is a pharmaceutically acceptable salt of 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine.

4. The method of claim 2, wherein the compound is a prodrug of 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine.

5. The method of claim 2, wherein the compound is administered in an enantiomerically enriched form.

6. The method of claim 1, wherein the compound is at least 95% in its designated enantiomeric.

7. The method of claim 1, wherein the compound is administered in a pharmaceutically acceptable carrier.

8. The method of claim 2, wherein the pharmaceutically acceptable carrier is suitable for oral delivery.

9. The method of claim 7, wherein the pharmaceutically acceptable carrier is suitable for intravenous delivery.

10. The method of claim 7, wherein the pharmaceutically acceptable carrier is suitable for parenteral delivery.

11. The method of claim 8, wherein the pharmaceutically acceptable carrier is suitable for intradermal delivery.

12. The method of claim 7, wherein the pharmaceutically acceptable carrier is suitable for subcutaneous delivery.

13. The method of claim 7, wherein the pharmaceutically acceptable carrier is suitable for topical delivery.

14. The method of claim 7, wherein the compound is in the form of a dosage unit.

15. The method of claim 7, wherein the dosage unit contains 10 to 1500 mg of the compound.

16. The method of claim 14 or 15, wherein the dosage unit is a tablet or capsule.