Claims for Patent: 6,395,716

Summary for Patent: 6,395,716

Title:	.beta.-L-2'-deoxy-nucleosides for the treatment of hepatitis B
Abstract:	This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2'-deoxy-.beta.-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2'-deoxy-.beta.-L-erythro-pentofuranonucleoside has the formula: ##STR1## wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2'-deoxy-.beta.-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2'-deoxy-.beta.-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.
Inventor(s):	Gosselin; Gilles (Montpellier, FR), Imbach; Jean-Louis (Montpellier, FR), Bryant; Martin L. (Carlisle, MA)
Assignee:	Novirio Pharmaceuticals Limited (Grand Cayman, KY) Centre National da la Recherche Scientifique (Paris, FR)
Application Number:	09/371,747
Patent Claims:	1. A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of .beta.-L-2'-deoxycytidine of the formula: ##STR20## or pharmaceutically acceptable salt thereof. 2. A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of .beta.-L-thymidine of the formula: ##STR21## or pharmaceutically acceptable salt thereof. 3. A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a combination of the following nucleosides: ##STR22## or a pharmaceutically acceptable salt thereof. 4. A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a compound of the formula: ##STR23## or its pharmaceutically acceptable salt thereof, in combination or alternation with an effective amount of a compound selected from the group consisting of .beta.-L-2-hydroxymethyl-5-(cytosin-1-yl)-1,3-oxathiolane (3TC), cis-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (FTC), .beta.-L-2'-fluoro-5-methyl-arabinouridine (L-FMAU), .beta.-D-2,6-diaminopurine dioxolane (DAPD), famciclovir, penciclovir, 2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl] -6H-purin-6-one (entecavir, BMS-200475), 9-[2-(phosphono-methoxy)ethyl]adenine (PMEA, adefovir, dipivoxil); lobucavir, ganciclovir and ribavirin. 5. A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a compound of the formula: ##STR24## or its pharmaceutically acceptable salt thereof, in combination or alternation with an effective amount of a compound selected from the group consisting of .beta.-L-2-hydroxymethyl-5-(cytosin-1-yl)-1,3-oxathiolane (3TC), cis-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (FTC), .beta.-L-2'-fluoro-5-methyl-arabinouridine (L-FMAU), .beta.-D-2,6-diaminopurine dioxolane (DAPD), famciclovir, penciclovir, 2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl] -6H-purin-6-one (entecavir, BMS-200475), 9-[2-(phosphono-methoxy)ethyl]adenine (PMEA, adefovir, dipivoxil); lobucavir, ganciclovir and ribavirin. 6. The method of claim 1, wherein the .beta.-L-2'-deoxycytidine is at least 95% in its designated enantiomeric form. 7. The method of claim 1, wherein the .beta.-L-2'-deoxycytidine is administered in a pharmaceutically acceptable carrier. 8. The method of claim 7, 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 7, 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 14, 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. 17. The method of claim 2, wherein the .beta.-L-thymidine is at least 95% in its designated enantiomeric form. 18. The method of claim 2, wherein the .beta.-L-thymidine is administered in a pharmaceutically acceptable carrier. 19. The method of claim 17, wherein the pharmaceutically acceptable carrier is suitable for oral delivery. 20. The method of claim 17, wherein the pharmaceutically acceptable carrier is suitable for intravenous delivery. 21. The method of claim 17, wherein the pharmaceutically acceptable carrier is suitable for parenteral delivery. 22. The method of claim 17, wherein the pharmaceutically acceptable carrier is suitable for intradermal delivery. 23. The method of claim 17, wherein the pharmaceutically acceptable carrier is suitable for subcutaneous delivery. 24. The method of claim 17, wherein the pharmaceutically acceptable carrier is suitable for topical delivery. 25. The method of claim 17, wherein the compound is in the form of a dosage unit. 26. The method of claim 25, wherein the dosage unit contains 10 to 1500 mg of the compound. 27. The method of claim 25 or 26, wherein the dosage unit is a tablet or capsule.