HIV-1 mutations selected for by β-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine

• US 7,635,690 B2
• Filed: 10/03/2006
• Issued: 12/22/2009
• Est. Priority Date: 01/22/1999
• Status: Expired due to Fees

• Current Assignee: Emory University
• Original Assignee: Emory University
• Inventors: Hammond, Jennifer L., Schinazi, Raymond F., Liotta, Dennis C., Mellors, John W.
• Primary Examiner(s): Crane; Lawrence E
• Application Number:
  US11/542,044
• Publication Number:
  US 20070025964A1
• Time in Patent Office: 1,176 Days
• Field of Search: None
• US Class Current: 514/45
• 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 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• 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 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The present invention discloses a method for treating HIV that includes administering β-D-D4FC or its pharmaceutically acceptable salt or prodrug to a human in need of therapy in combination or alternation with a drug that induces a mutation in HIV-1 at a location other than the 70(K to N), 90 or the 172 codons of the reverse transcriptase region. Also disclosed is a method for using β-D-D4FC as “salvage therapy” to patients which exhibit drug resistance to other anti-HIV agents. β-D-D4FC can be used generally as salvage therapy for any patient which exhibits resistance to a drug that induces a mutation at other than the 70(K to N), 90 or the 172 codons.

Claims

1. A method for treating an HIV infection in a human in need thereof comprising administering an effective amount of β

-D-D4FC or its pharmaceutically acceptable ester or salt to the human, optionally in a pharmaceutically acceptable carrier, in combination or alternation with an effective amount of a second drug selected from the group consisting of abacavir, indinavir, nelfinavir, saquinavir, amprenavir, efavirenz, delavirdine and nevirapine for the treatment of an HIV infection in a human.

2. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is indinavir.

3. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is nelfinavir.

4. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is saquinavir.

5. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is amprenavir.

6. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is efavirenz.

7. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is delavirdine.

8. The method of claim 1 wherein the second drug in combination or alternation with β

-D-D4FC is nevirapine.

9. The method of claim 1, wherein β

-D-D4FC and the second drug are in a pharmaceutically acceptable carrier.

10. The method according to claim 9, wherein the pharmaceutically acceptable carrier is suitable for oral delivery, intravenous delivery, parenteral delivery, intradermal delivery, subcutaneous delivery or topical delivery.

11. The method of claim 1, wherein β

-D-D4FC and the second drug are in the form of a dosage unit.

12. The method of claim 11, wherein the dosage unit contains 10 to 1500 mg of each compound.

13. The method of claim 11, wherein the dosage unit is a tablet or a capsule.

14. The method of claim 1 wherein β

-D-D4FC and the second drug are administered in combination.

15. The method of claim 1 wherein β

-D-D4FC and the second drug are administered in alternation.

16. A pharmaceutical composition comprising an effective amount of β

-D-D4FC or its pharmaceutically acceptable ester or salt, in a pharmaceutically acceptable carrier, in combination with an effective amount of a second drug selected from the group consisting of abacavir, indinavir, nelfinavir, saquinavir, amprenavir, efavirenz, delavirdine and nevirapine.

17. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is indinavir.

18. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is nelfinavir.

19. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is saquinavir.

20. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is amprenavir.

21. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is efavirenz.

22. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is delavirdine.

23. The pharmaceutical composition of claim 16 wherein the second drug in combination with β

-D-D4FC is nevirapine.

24. The pharmaceutical composition according to claim 16, wherein the pharmaceutically acceptable carrier is suitable for oral delivery, intravenous delivery, parenteral delivery, intradermal delivery, subcutaneous delivery or topical delivery.

25. The pharmaceutical composition according to claim 16, wherein β

-D-D4FC and the second drug are in the form of a dosage unit.

26. The pharmaceutical composition according to claim 25, wherein the dosage unit contains 10 to 1500 mg of each compound.

27. The pharmaceutical composition according to claim 25, wherein the dosage unit is a tablet or a capsule.