Claims for Patent: 8,735,345

Summary for Patent: 8,735,345

Title:	Therapeutic composition
Abstract:	Embodiments disclosed in the present application relate to a composition that can include a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof. Additional embodiments disclosed relate to methods for treating a disease condition such as a hepatitis C virus infection, liver fibrosis and/or impaired liver function with a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof.
Inventor(s):	Porter; Steven B. (Mill Valley, CA), Bradford; Williamson Ziegler (Ross, CA), Smith; Patrick F. (Pleasanton, CA), Yetzer; Ellen S. (San Francisco, CA), De La Rosa; Abel (Alpharetta, GA), Rogers; Michael D. (Chapel Hill, NC), Symonds; William T. (Cary, NC)
Assignee:	Hoffmann la Roche Inc. (Nutley, NJ) Pharmasset, Inc. (Princeton, NJ) Roche Palo Alto LLC (Palo Alto, CA)
Application Number:	12/713,497
Patent Claims:	1. A composition comprising a first compound, or a pharmaceutically acceptable salt thereof, wherein the first compound is ##STR00001## and a second compound, or a pharmaceutically acceptable salt thereof, wherein the second compound is ##STR00002## 2. A composition consisting essentially of a first compound, or a pharmaceutically acceptable salt thereof, wherein the first compound is ##STR00003## and a second compound, or a pharmaceutically acceptable salt thereof, wherein the second compound is ##STR00004## 3. The composition of claim 1, further comprising a pharmaceutically acceptable excipient, diluent or carrier. 4. The composition of claim 1, wherein the composition comprises an amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 9000 mg to about 50 mg. 5. The composition of claim 1, wherein the composition comprises an amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 5000 mg to about 150 mg. 6. The composition of claim 1, wherein the composition comprises an amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 2000 mg to about 300 mg. 7. The composition of claim 1, wherein the composition comprises an amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 1000 mg to about 450 mg. 8. The composition of claim 1, wherein the composition comprises an amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 1000 mg to about 500 mg. 9. The composition of claim 1, wherein the composition comprises an amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 2000 mg to about 2 mg. 10. The composition of claim 1, wherein the composition comprises an amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 1600 mg to about 25 mg. 11. The composition of claim 1, wherein the composition comprises an amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 500 mg to about 50 mg. 12. The composition of claim 1, wherein the composition comprises an amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 200 mg to about 100 mg. 13. The composition of claim 1, wherein the composition comprises a total amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 1% to about 99% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 14. The composition of claim 1, wherein the composition comprises a total amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 5% to about 90% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 15. The composition of claim 1, wherein the composition comprises a total amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 10% to about 80% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 16. The composition of claim 1, wherein the composition comprises a total amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 20% to about 70% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 17. The composition of claim 1, wherein the composition comprises a total amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 30% to about 60% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 18. The composition of claim 1, wherein the composition comprises a total amount of the first compound, or a pharmaceutically acceptable salt thereof, in the range of about 40% to about 50% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 19. The composition of claim 13, wherein the composition comprises a total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 1% to about 99% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 20. The composition of claim 13, wherein the composition comprises a total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 5% to about 90% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 21. The composition of claim 13, wherein the composition comprises a total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 10% to about 80% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 22. The composition of claim 13, wherein the composition comprises a total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 20% to about 70% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 23. The composition of claim 13, wherein the composition comprises a total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 30% to about 60% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 24. The composition of claim 13, wherein the composition comprises a total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the range of about 40% to about 50% (weight/weight) based on the sum of the total amount of the first compound, or a pharmaceutically acceptable salt thereof, and the total amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition. 25. The composition of claim 1, wherein the amount of the first compound, or a pharmaceutically acceptable salt thereof, in the composition is less than the amount of the first compound, or a pharmaceutically acceptable salt thereof, needed to achieve substantially the same viral load reduction as when the first compound, or a pharmaceutically acceptable salt thereof, is administered as monotherapy. 26. The composition of claim 1, wherein the amount of the second compound, or a pharmaceutically acceptable salt thereof, in the composition is less than the amount of the second compound, or a pharmaceutically acceptable salt thereof, needed to achieve substantially the same viral load reduction as when the second compound, or a pharmaceutically acceptable salt thereof, is administered as monotherapy. 27. The composition of claim 1, wherein the composition further comprises one or more additional therapeutic agents. 28. The composition of claim 27, wherein the one or more additional therapeutic agents are selected from the group consisting of a nucleoside analog, pirfenidone, a pirfenidone analog, an NS5B RNA-dependent RNA polymerase inhibitor, a tumor necrosis factor antagonist, thymosin-.alpha., interferon-gamma (IFN-.gamma.), interferon-alpha (IFN-.alpha.), 3'-azidothymidine, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, 2-,3-didehydro-2',3'-dideoxythymidine, combivir, abacavir, adefovir dipivoxil, cidofovir, ritonavir, an inosine monophosphate dehydrogenase inhibitor, an interferon, an additional NS3 protease inhibitor, a NS5B polymerase inhibitor, and an NS3 helicase inhibitor. 29. The composition of claim 28, wherein the nucleoside analog is selected from the group consisting of ribavirin, levovirin, viramidine, an L-nucleoside, and isatoribine. 30. The composition of claim 28, wherein the tumor necrosis factor antagonist is selected from the group consisting of etanercept, infliximab, and adalimumab. 31. The composition of claim 28, wherein the thymosin-.alpha. is in an amount in the range of from about 1.0 mg to about 1.6 mg. 32. The composition of claim 28, wherein the IFN-.gamma. is in an amount in the range of from about 10 .mu.g to about 300 .mu.g. 33. The composition of claim 28, wherein the IFN-.alpha. is monoPEG (30 kD, linear)-ylate consensus. 34. The composition of claim 28, wherein the IFN-.alpha. is selected from the group consisting of a 40 kD branched mono-methoxy PEG conjugate of interferon .alpha.-2b and a 12 kD mono-methoxy PEG conjugate of interferon .alpha.-2b. 35. The composition of claim 28, wherein the IFN-.alpha. is INFERGEN consensus IFN-.alpha.. 36. The composition of claim 28, wherein the additional NS3 protease inhibitor is selected from ##STR00005## 37. The composition of claim 1, wherein the composition does not comprise ribavirin. 38. The composition of claim 1, wherein the composition does not comprise an interferon. 39. The composition of claim 38, wherein the interferon is a pegylated interferon. 40. A method for ameliorating a disease condition in a patient population, comprising administering a therapeutically effective amount of one or more compositions of claim 1 to a subject suffering from the disease condition, wherein the disease condition is selected from the group consisting of a hepatitis C virus infection, and liver fibrosis. 41. A method for ameliorating a disease condition in a patient population comprising administering a therapeutically effective amount of a first compound, or a pharmaceutically acceptable salt thereof, wherein the first compound is ##STR00006## and a therapeutically effective amount of a second compound, or a pharmaceutically acceptable salt thereof, wherein the second compound is ##STR00007## to a subject suffering from the disease condition, wherein the disease condition is selected from the group consisting of a hepatitis C virus infection, and liver fibrosis. 42. The method of claim 41, wherein the first compound, or a pharmaceutically acceptable salt thereof, is administered before the second compound, or a pharmaceutically acceptable salt thereof. 43. The method of claim 41, wherein the first compound, or a pharmaceutically acceptable salt thereof, is administered after the second compound, or a pharmaceutically acceptable salt thereof. 44. The method of claim 41, wherein the first compound, or a pharmaceutically acceptable salt thereof, is administered at approximately the same time as the second compound, or a pharmaceutically acceptable salt thereof. 45. The method of claim 41, wherein the first compound, or a pharmaceutically acceptable salt thereof, and the second compound, or a pharmaceutically acceptable salt thereof, are together in one dosage form. 46. The method of claim 41, wherein the first compound, or a pharmaceutically acceptable salt thereof, and the second compound, or a pharmaceutically acceptable salt thereof, are in separate dosage forms. 47. The method of claim 40, wherein the disease condition is a hepatitis C viral infection. 48. The method of claim 40, wherein the method further comprises administering an effective amount of an additional nucleoside analog. 49. The method of claim 48, wherein the additional nucleoside analog is selected from the group consisting of ribavirin, levovirin, viramidine, an L-nucleoside, and isatoribine. 50. The method of claim 40, wherein the method further comprises administering an effective amount of pirfenidone or a pirfenidone analog. 51. The method of claim 40, wherein the method further comprises administering an effective amount of an NS5B RNA-dependent RNA polymerase inhibitor. 52. The method of claim 40, wherein the method further comprises administering an effective amount of a tumor necrosis factor antagonist selected from the group consisting of etanercept, infliximab, and adalimumab. 53. The method of claim 40, wherein the method further comprises administering an effective amount of thymosin-.alpha.. 54. The method of claim 53, wherein the thymosin-.alpha. is in an amount in the range of from about 1.0 mg to about 1.6 mg. 55. The method of claim 40, wherein the method further comprises administering an effective amount of interferon-gamma (IFN-.gamma.). 56. The method of claim 55, wherein the IFN-.gamma. is administered subcutaneously in an amount in the range of from about 10 .mu.g to about 300 .mu.g. 57. The method of claim 40, wherein the method further comprises administering an effective amount of interferon-alpha (IFN-.alpha.). 58. The method of claim 57, wherein the IFN-.alpha. is monoPEG (30 kD, linear)-ylate consensus administered at a dosing interval in the range of every 8 days to every 14 days. 59. The method of claim 57, wherein the IFN-.alpha. is monoPEG (30 kD, linear)-ylated consensus IFN-.alpha. administered at a dosing interval of once every 7 days. 60. The method of claim 57, wherein the IFN-.alpha. is selected from the group consisting of a 40 kD branched mono-methoxy PEG conjugate of interferon .alpha.-2b and a 12 kD mono-methoxy PEG conjugate of interferon .alpha.-2b. 61. The method of claim 57, wherein the IFN-.alpha. is INFERGEN consensus IFN-.alpha.. 62. The method of claim 40, wherein the method further comprises administering an effective amount of an agent selected from 3'-azidothymidine, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, 2-,3-didehydro-2',3'-dideoxythymidine, combivir, abacavir, adefovir dipivoxil, cidofovir, ritonavir, and an inosine monophosphate dehydrogenase inhibitor. 63. The method of claim 40, wherein the method further comprises administering an effective amount of an interferon, an additional NS3 protease inhibitor, an NS5B polymerase inhibitor, or an NS3 helicase inhibitor. 64. The method of claim 63, wherein the additional NS3 protease inhibitor is selected from ##STR00008## 65. The method of claim 40, wherein the patient population is administered pegylated interferon after administration of the first compound, or a pharmaceutically acceptable salt thereof, and the second compound, or a pharmaceutically acceptable salt thereof, is complete. 66. The method of claim 40, wherein the patient population is administered ribavirin after administration of the first compound, or a pharmaceutically acceptable salt thereof, and the second compound, or a pharmaceutically acceptable salt thereof, is complete. 67. The method of claim 40, wherein the method does not include administering an additional agent. 68. The method of claim 67, wherein the additional agent is ribavirin. 69. The method of claim 67, wherein the additional agent is an interferon. 70. The method of claim 69, wherein the interferon is a pegylated interferon.

Details for Patent 8,735,345

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Kadmon Pharmaceuticals Llc	INFERGEN	interferon alfacon-1	Injection	103663	10/06/1997		2039-02-26
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2039-02-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2039-02-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2039-02-26
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2039-02-26