METHODS FOR TREATING HCV

• US 20130243726A1
• Filed: 05/01/2013
• Published: 09/19/2013
• Est. Priority Date: 09/16/2011
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Ray, Adrian S., Watkins, William J., Link, John O., Oldach, David W., Delaney, William E. IV
• Granted Patent: US 9,393,256 B2
• Time in Patent Office: Days
• US Class Current: 424/85.4
• 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 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• 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 38/06 Tripeptides
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention folates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions,

Claims

10. A method of treating an HCV infection in a human, comprising administering to the human:

1) a compound 10 or a pharmaceutically acceptable salt thereof and

     2) a compound 5 or a pharmaceutically acceptable salt thereof, or compound 8 or a pharmaceutically acceptable salt thereof.

11. The method of claim 10 wherein:

1) compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound 5 or a pharmaceutically acceptable salt thereof are administered.

12. The method of claim 10 wherein:

1) a compound 10 or a pharmaceutical acceptable salt thereof, and

     2) a compound 8 or a pharmaceutically acceptable salt thereof are administered.

13. The method of claim 10 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof,

     2) a compound 5 or a pharmaceutically acceptable salt thereof, and

     3) a compound 8 or a pharmaceutically acceptable salt thereof are administered.

30. The method of any one of claims 10-29 wherein an interferon is not administered to the human.

31. The method of any one of claims 10-29 further comprising administering ribavirin to the human.

32. The method of any one of claims 10-29 further comprising administering one or more additional agents selected from ribavirin, an interferon, alpha-glucosidase 1 inhibitors, hepatoprotectants, TLR-7 agonists, cyclophilin inhibitors, HCV viral entry inhibitors, HCV maturation inhibitors, and HCV IRES inhibitors fo the human.

15. A method of ameliorating one or more symptoms of an HCV infection in a human, comprising administering to the human:

1) a compound 10 or a ptorniaceuficaliy acceptable salt thereof and

     2) a compound 5 or a pharmaceutically acceptable salt thereof, or compound 8 or a pharmaceutically acceptable salt thereof.

16. The method of claim 15 wherein:

1) compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound 5 or a pharmaceutically acceptable salt thereof are administered.

17. The method of claim 15 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound or a pharmaceutically acceptable salt thereof are administered.

18. The method of claim 15 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof,

     2) a compound 5 or a pharmaceutically acceptable salt thereof, and

     3) a compound 6 or a pharmaceutically acceptable salt thereof are administered.

20-1. The method of claim 25 wherein;

1) compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound 5 or a pharmaceutically acceptable salt thereof are administered.

25. A method for reducing emergence of HCV quaslspecles with resistance to coadministered oral antiviral agents in a human, comprising administering to the human:

1) a compound 10 or a pharmaceutically acceptable salt thereof and

     2) a compound 5 or a pharmaceutically acceptable salt thereof, or compound 6 or a pharmaceutically acceptable salt thereof.

1. A composita comprising:

1) compound 10 or a pharmaceutically acceptable salt thereof and

     2) compound 5 or a pharmaceutically acceptable salt thereof, or compound 6 or a pharmaceutically acceptable salt thereof.

2. The composition of claim 1 which composes:

1) compound 10 or a pharmaceutically acceptable salt thereof, and

     2) compound 5 or a pharmaceutically acceptable salt thereof.

3. The composition of claim 1 which composes:

1) compound 10 or a pharmaceutically acceptable salt thereof, and

     2) compound 8 or a pharmaceutically acceptable salt thereof.

4. The composition of claim 1 which comprises:

1) compound 10 or a pharmaceutically acceptable salt thereof,

     2) compound 5 or a pharmaceutically acceptable salt thereof, and

     3) compound 6 or a pharmaceutically acceptable salt thereof.

5. The composition of any one of claims 1-4 which further comprises one or more pharmaceutically acceptable diluents or carriers.

6. The composition of claim 5 which is formulated as a unit dosage form for once daily administration.

7. The composition of any one of claims 5-8 which is formulated for oral administration.

8. The composition of any one of claims 5-7 which is formulated, as a tablet.

9. The composition of any one of claims 1-8 which further comprises ribavirin.

14. The method of claim 10 wherein a composition as described in any one of claims 1-8 is administered to the human.

19. The method of claim 15 wherein a composition as described in any one of claims 1-8 is administered to the human.

20. A method of reducing viral load in a human with HCV, comprising administering to the human:

1) a compound 10 or a pharmaceutically acceptable salt thereof and

     2) a compound 5 or a pharmaceutically acceptable salt thereof, or compound 6 or a pharmaceutically acceptable salt thereof.

21. The method of claim 20 wherein:

1) compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound 5 or a pharmaceutically acceptable salt thereof are administered.

22. The method of claim 20 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound or a pharmaceutically acceptable salt thereof are administered,

23. The method of claim 20 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof,

     2) a compound 5 or a pharmaceutical acceptable salt thereof, and

     3) a compound 6 or a pharmaceutically acceptable salt thereof are administered.

24. The method of claim 20 wherein a composition as described in any one of claims 1-8 is administered to the human.

27. The method of claim 25 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof, and

     2) a compound 8 or a pharmaceutically acceptable salt thereof are administered.

28. The method of claim 25 wherein:

1) a compound 10 or a pharmaceutically acceptable salt thereof,

     2) a compound 5 or a pharmaceutically acceptable salt thereof, and

     3) a compound 8 or a pharmaceutically acceptable salt thereof are administered.

29. The method of claim 25 wherein a composition as described in any one of claims 1-3 is administered to the human.

33. A composition as described in any one of claims 1-9 for use in medical therapy.

34. A composition as described in any one of claims 1-9 for the prophylactic or therapeutic treatment of an HCV infection.

35. The use of a composition as described in any one of claims 1-9 to prepare a medicament for treating an HCV infection in a human,

36. The use of a composition as described in any one of claims 1-9 to prepare a medicament for ameliorating one or more symptoms of an HCV infection in a human.

37. A composition as described in any one of claims 1-9 for reducing viral load.

38. The use of a composition as described in any one of claims 1-9 to prepare a medicament for reducing viral load in a human,

39. A composition as described in any one of claims 1-9 for reducing emergence of HCV quasispedes with resistance to coadministered oral antiviral agents.

41. The composition of claim 34, 37, or 39 which is not for administration with an interferon.

42. The composition of claim 34, 37, or 39 which is for administration with ribavirin.

43. The composition of claim 34, 37, or 39 which is for administration with one or more additional agents selected from ribavirin, an interferon, alpha-glucosidase 1 inhibitors, hepatoprotectents, TLR-7 agonists, cyclophin inhibitors, HCV viral entry inhibitors, HCV maturation inhibitors, and HCV IRES inhibitors.

44. The use of any one of claims 35,36, 38, and 40 wherein the medicament is not for administration with an interferon.

45. The use of any one of claims 35,36, 38, and 40 wherein the medicament is for administration with ribavirin.

46. The use of any one of claims 35,38, 38, and 40 wherein the medicament is for administration with one or more additional agents selected from ribavirin, an interferon, alpha-glucosidase 1 inhibitors, hepatoprotectants, TLR-7 agonists, cyclophilin inhibitors, HCV viral entry inhibitors, HCV maturation inhibitors, and HCV IRES inhibitors.

40. The use of a composition as described in any one of ciaims 1-9 to prepare a medicament for reducing emergence of HCV quasispedes with resistance to coadministered oral antiviral agents in a human.