COMBINATION THERAPY COMPRISING TENOFOVIR ALAFENAMIDE HEMIFUMARATE AND COBICISTAT FOR USE IN THE TREATMENT OF VIRAL INFECTIONS

• US 20150105350A1
• Filed: 02/01/2013
• Published: 04/16/2015
• Est. Priority Date: 02/03/2012
• Status: Abandoned Application

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Ramanathan, Srinivasan
• Application Number:
  US14/376,116
• Publication Number:
  US 20150105350A1
• Time in Patent Office: Days
• US Class Current: 514/81
• 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 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• 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

Abstract

The use of the hemifumarate form of {9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine} (tenofovir alafenamide hemifumarate) in combination with cobicistat is disclosed. In addition, the combination of tenofovir alafenamide hemifumarate, cobicistat, emtricitabine, and elvitegravir, and the combination of tenofovir alafenamide hemifumarate, cobicistat, emtricitabine, and darunavir, are disclosed.

Claims

1. A composition comprising:

cobicistat, or a pharmaceutically acceptable salt thereof; and

tenofovir alafenamide hemifumarate.

2. The composition of claim 1 comprising:

50-500 mg of cobicistat, or a pharmaceutically acceptable salt thereof; and

3-40 mg of tenofovir alafenamide hemifumarate.

3. The composition of claim 1, further comprising a pharmaceutically acceptable carrier or diluent.

4. A method of treating a viral infection in a human comprising administering a composition of claim 1 to the human.

12. A method of boosting an anti-viral effect of tenofovir alafenamide hemifumarate in a human comprising administering a composition of claim 1 to the human.

15. A method of inhibiting Pgp-mediated intestinal secretion of tenofovir alafenamide hemifumarate in a human comprising administering a composition of claim 1 to the human.

5. A method of treating a viral infection in a human comprising coadministering cobicistat, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide hemifumarate, to the human.

18. The method of claim 5, wherein the viral infection is human immunodeficiency virus (HIV) or Hepatitis B virus (HBV).

6. A method of inhibiting activity of a retroviral reverse transcriptase comprising coadministering cobicistat, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide hemifumarate.

7. The method of claim 6, wherein the coadministering of cobicistat, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide hemifumarate, is in a human.

8-11. -11. (canceled)

13. A method of boosting an anti-viral effect of tenofovir alafenamide hemifumarate in a human comprising coadministering cobicistat, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide hemifumarate to the human.

14. The method of claim 13, wherein 50-500 mg of cobicistat, or a pharmaceutically acceptable salt thereof, is coadministered with 3-40 mg of tenofovir alafenamide hemifumarate.

20. The method of claim 13, wherein the virus is human immunodeficiency virus (HIV) or Hepatitis B virus (HBV).

16. A method of inhibiting Pgp-mediated intestinal secretion of tenofovir alafenamide hemifumarate in a human by coadministration of cobicistat, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide hemifumarate.

17. The method of claim 16, wherein 50-500 mg of cobicistat, or a pharmaceutically acceptable salt thereof, is coadministered with 3-40 mg of tenofovir alafenamide hemifumarate.

19. (canceled)

21. A composition comprising:

(a) tenofovir alafenamide hemifumarate;

(b) cobicistat, or a pharmaceutically acceptable salt thereof;

(c) emtricitabine; and

(d) elvitegravir.

23. A method of treating a viral infection in a human comprising administering a composition of claim 21 to the human.

22. A composition comprising:

(a) 3-40 mg tenofovir alafenamide hemifumarate;

(b) 50-500 mg cobicistat, or a pharmaceutically acceptable salt thereof;

(c) 50-500 mg emtricitabine; and

(d) 50-500 mg elvitegravir.

24. A method of treating a viral infection in a human comprising coadministering (a) tenofovir alafenamide hemifumarate;

(b) cobicistat, or a pharmaceutically acceptable salt thereof;

(c) emtricitabine; and

(d) elvitegravir to the human.

25. The method of claim 24 comprising coadministering (a) 3-40 mg tenofovir alafenamide hemifumarate;

(b) 50-500 mg cobicistat, or a pharmaceutically acceptable salt thereof;

(c) 50-500 mg emtricitabine; and

(d) 50-500 mg elvitegravir to the human.

31. The method of claim 24, wherein the viral infection is human immunodeficiency virus (HIV) or Hepatitis B virus (HBV).

26-30. -30. (canceled)

32. (canceled)