Method of treating hepatitis delta virus infection

• US 7,511,027 B2
• Filed: 11/22/2002
• Issued: 03/31/2009
• Est. Priority Date: 03/29/2000
• Status: Expired due to Fees

• Current Assignee: Georgetown University, The University of Georgia Research Foundation, Inc.
• Original Assignee: Georgetown University, The University of Georgia Research Foundation, Inc.
• Inventors: Gerin, John L., Tennant, Bud C., Cote, Paul J., Casey, John L., Chu, Chung K., Korba, Brent E.
• Primary Examiner(s): Epps-Ford; Janet L
• Application Number:
  US10/302,814
• Publication Number:
  US 20030158149A1
• Time in Patent Office: 2,321 Days
• Field of Search: None
• 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 infected with hepatitis delta virus an effective amount of a 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine or a pharmaceutically acceptable salt thereof, that reduces the level of hepatitis B surface or preS1 antigen in the host 100-fold or more relative to pretreatment value, wherein the treatment results in the reduction of hepatitis delta virus in the host.

4. The method of claim 1, further comprising administering the compound in combination or alternation with interferon α

.

5. The method of claim 1 wherein the level of hepatitis B surface antigen is reduced 200 fold.

6. The method of claim 1 wherein the level of hepatitis B surface antigen is reduced 500 fold.

9. The method of claim 1 wherein the level of preS1 is reduced 200 fold.

10. The method of claim 1 wherein the level of preS1 is reduced 500 fold.

11. The method of claim 4 wherein the compounds are administered in combination.

12. The method of claim 4 wherein the compounds are administered in alternation.

13. The method of claim 1 wherein the compound is in a pharmaceutically acceptable carrier or diluent.

14. The method of claim 13 wherein the compound is administered in a unit dose.

15. The method of claim 14 wherein the unit dose contains 50 to 1000 mg of the compound.

16. The method of claim 13 wherein pharmaceutically acceptable carrier is suitable for oral delivery.

17. The method of claim 13 wherein pharmaceutically acceptable carrier is suitable for intravenous delivery.

18. The method of claim 13 wherein pharmaceutically acceptable carrier is suitable for parenteral delivery.

19. The method of claim 13 wherein pharmaceutically acceptable carrier is suitable for topical delivery.

20. The method of claim 1 wherein the 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine is administered.

2. A method for the treatment of hepatitis delta infection comprising:

administering to a host infected with hepatitis delta virus an effective amount of a 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine or a pharmaceutically acceptable salt thereof, that reduces the level of preS1 antigen in the host 100-fold or more relative to pretreatment value, wherein the treatment results in the reduction of hepatitis delta virus in the host.

21. The method of claim 2 wherein the 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine is administered.

3. A method for the treatment of HDV infected host comprising administering of an effective amount of a 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine or a pharmaceutically acceptable salt thereof that reduces HBsAg in the infected host to not more than approximately 1 microgram per milliliter, as measured in serum or plasma, wherein the treatment results in the reduction of hepatitis delta virus in the host.

7. The method of claim 3 wherein the level of hepatitis B surface antigen is reduced to not more than 0.5 microgram per milliliter, as measured in serum or plasma.

8. The method of claim 3 wherein the level of hepatitis B surface antigen is reduced to not more than 0.1 microgram per milliliter, as measured in serum or plasma.

22. The method of claim 3 wherein the 2′

-fluoro-5-methyl-β

-L-arabinofuranosyl-uridine is administered.