Combination therapy to treat hepatitis B virus

• US 6,528,515 B1
• Filed: 11/02/1999
• Issued: 03/04/2003
• Est. Priority Date: 11/02/1998
• Status: Expired due to Term

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Triangle Pharmaceuticals, Inc. (Gilead Sciences Inc.)
• Inventors: Furman, Phillip A., Rousseau, Franck, Painter, George R. III, Barry, David W.
• Primary Examiner(s): Travers, Russell
• Assistant Examiner(s): Wang, Shengjun
• Application Number:
  US09/432,247
• Time in Patent Office: 1,218 Days
• Field of Search: 514/274, 514/261, 514/262, 514/263, 514/264
• US Class Current: 514/274
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention is directed to a method for treating hepatitis B virus infection in humans comprising administering a synergistically effective amount of agents having known anti-hepatitis B virus activity in combination or alternation. Specifically, the invention is directed to a method for treating hepatitis B virus infection comprising administering FTC in combination or alternation with penciclovir, famciclovir or Bis-POM-PMEA. Additionally, the invention is directed to a method for treating hepatitis B virus infection comprising administering L-FMAU in combination or alternation with DAPD, penciclovir or Bis-POM-PMEA. The invention is further directed to a method for treating hepatitis B virus infection comprising administering DAPD in combination or alternation with Bis-POM-PMEA.

Claims

1. A method for the treatment of hepatitis B virus in a human comprising administering in combination or alternation a synergistically effective amount of β

-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (β

-FTC) or a pharmaceutically acceptable salt, ester, or prodrug thereof with an effective amount of penciclovir.

2. The method of claim 1, wherein the β

-FTC is in the form of the (−

)-optical isomer ((−

)-β

-FTC).

3. The method of claim 2 wherein the (−

)-β

-FTC is in substantially pure form including no more than about 5% of the (+)-enantiomer.

4. The method of claim 2 wherein the (−

)-β

-FTC is in substantially pure form including no more than about 1% of the (+)-enantiomer.

5. The method of claim 2 wherein the (−

)-β

-FTC is present in a nucleoside composition comprising approximately 95% to 100% of (−

)-β

-FTC.

6. The method of claim 2 wherein the (−

)-β

-FTC is present in a nucleoside composition comprising greater than 97% of (−

)-β

-FTC.

7. The method of claim 2 wherein the (−

)-β

-FTC and penciclovir are administered as oral tablets.

8. The method of claim 2 wherein the (−

)-β

-FTC and penciclovir are administered in combination.

9. The method of claim 2 wherein the (−

)-β

-FTC and penciclovir are administered in alternation.

10. The method of claim 2 wherein (−

)-β

-FTC is administered.

11. The method of claim 2 wherein a pharmaceutically acceptable salt of (−

)-β

-FTC is administered.

12. The method of claim 10 wherein the (−

)-β

-FTC is in substantially pure form including no more than about 5% of the (+)-enantiomer.

13. The method of claim 10 wherein the (−

)-β

-FTC is in substantially pure form including no more than about 1% of the (+)-enantiomer.

14. The method of claim 11 wherein the pharmaceutically acceptable salt of (−

)-β

-FTC is in substantially pure form including no more than about 5% of the (+)-enantiomer.

15. The method of claim 11 wherein the pharmaceutically acceptable salt of (−

)-β

-FTC is in substantially pure form including no more than about 1% of the (+)-enantiomer.

16. The method of claim 10 wherein the (−

)-β

-FTC is present in a nucleoside composition comprising approximately 95% to 100% of (−

)-β

-FTC.

17. The method of claim 10 wherein the (−

)-β

-FTC is present in a nucleoside composition comprising greater than 97% of (−

)-β

-FTC.

18. The method of claim 11 wherein the pharmaceutically acceptable salt of (−

)-β

-FTC is present in a nucleoside composition comprising approximately 95% to 100% of the pharmaceutically acceptable salt of (−

)-β

-FTC.

19. The method of claim 11 wherein the pharmaceutically acceptable salt of (−

)-β

-FTC is present in a nucleoside composition comprising greater than 97% of the pharmaceutically acceptable salt of (−

)-β

-FTC.