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

• US 7,115,584 B2
• Filed: 01/23/2003
• Issued: 10/03/2006
• Est. Priority Date: 01/22/1999
• Status: Expired due to Fees

• Current Assignee: Emory University
• Original Assignee: Emory University
• Inventors: Schinazi, Raymond F., Liotta, Dennis C., Mellors, John W., Hammond, Jennifer L.
• Primary Examiner(s): Jiang, S. Anna
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US10/351,170
• Publication Number:
  US 20040082552A1
• Time in Patent Office: 1,349 Days
• Field of Search: 514 45- 51, 514/230.5, 514/261, 514/220, 514/231.5, 514/301, 514/473, 514/252, 514/253
• 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• 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 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 abacavir.

3. The method of claim 1, wherein β

-D-D4FC and abacavir are administered in a pharmaceutically acceptable carrier.

4. The method according to claim 3, wherein the pharmaceutically acceptable carrier is suitable for oral delivery, intravenous delivery, parenteral delivery, intradermal delivery, subcutaneous delivery or topical delivery.

5. The method of claim 1, wherein β

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

6. The method of claim 5, wherein the dosage unit contains 10 to 1500 mg of each compound.

7. The method of claim 5, wherein the dosage unit is a tablet or capsule.

8. The method of claim 1 wherein β

-D-D4FC and abacavir are administered in combination.

9. The method of claim 1 wherein β

-D-D4FC and abacavir are administered in alternation.

2. 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 abacavir.

10. The pharmaceutical composition according to claim 2, wherein the β

-D-D4FC and abacavir are in a pharmaceutically acceptable carrier.

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

12. The pharmaceutical composition according to claim 11, wherein the pharmaceutically acceptable carrier is suitable for oral delivery.

13. The pharmaceutical composition according to claim 11, wherein the pharmaceutically acceptable carrier is suitable for intravenous delivery.

14. The pharmaceutical composition according to claim 11, wherein the pharmaceutically acceptable carrier is suitable for parenteral delivery.

15. The pharmaceutical composition according to claim 11, wherein the pharmaceutically acceptable carrier is suitable for intradermal delivery.

16. The pharmaceutical composition according to claim 11, wherein the pharmaceutically acceptable carrier is suitable for topical delivery.

17. The pharmaceutical composition according to claim 2, wherein β

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

18. The pharmaceutical composition according to claim 17, wherein the dosage unit contains 10 to 1500 mg of each compound.

19. The pharmaceutical composition according to claim 17, wherein the dosage unit is a tablet or capsule.