Claims for Patent: 10,106,546

Summary for Patent: 10,106,546

Title:	Immunoregulatory agents
Abstract:	Compounds that modulate the oxidoreductase enzyme indoleamine 2,3-dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided.
Inventor(s):	Beck; Hilary Plake (Emerald Hills, CA), Jaen; Juan Carlos (Burlingame, CA), Osipov; Maksim (Belmont, CA), Powers; Jay Patrick (Pacifica, CA), Reilly; Maureen Kay (Belmont, CA), Shunatona; Hunter Paul (San Francisco, CA), Walker; James Ross (Menlo Park, CA), Zibinsky; Mikhail (Lodi, CA), Balog; James Aaron (Lambertville, NJ), Williams; David K. (Delran, NJ), Markwalder; Jay A. (Lahaska, PA), Cherney; Emily Charlotte (Newtown, PA), Shan; Weifang (Princeton, NJ), Huang; Audris (New Hope, PA)
Assignee:	Flexus Biosciences, Inc. (Princeton, NJ)
Application Number:	15/469,707
Patent Claims:	1. A compound that is (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00284## or a pharmaceutically acceptable salt thereof. 2. A compound that is (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide or a stereoisomer thereof or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1 that is (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00285## 4. The compound of claim 1 that is a pharmaceutically acceptable salt of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide. 5. A pharmaceutical composition comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00286## or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 6. A pharmaceutical composition comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 7. The pharmaceutical composition of claim 5 comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00287## 8. The pharmaceutical composition of claim 5 comprising a pharmaceutically acceptable salt of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide. 9. A combination comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00288## or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent. 10. A combination comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent. 11. The combination of claim 9, comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00289## 12. The combination of claim 9, comprising a pharmaceutically acceptable salt of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl- )propanamide. 13. The combination of claim 9, wherein said additional therapeutic agent is an immuno-oncology agent. 14. The combination of claim 13, wherein said immuno-oncology agent is selected from a CTLA-4 antagonist, a PD-1 antagonist, a PD-L1 antagonist, a LAG-3 antagonist, a CD137 agonist, a GITR agonist, an OX40 agonist, an OX40L antagonist, a CD40 agonist or antagonist, a CD27 agonist, a BTLA antagonist, a TIM-3 antagonist, an A2aR antagonist, a Killer Inhibitor Receptor antagonist, or a B7H3 antibody. 15. The combination of claim 14, wherein said immuno-oncology agent is a CTLA-4 antagonist. 16. The combination of claim 15, wherein said CTLA-4 antagonist is ipilimumab. 17. The combination of claim 14, wherein said immuno-oncology agent is a PD-1 antagonist. 18. The combination of claim 17, wherein said PD-1 antagonist is nivolumab. 19. The combination of claim 17, wherein said PD-1 antagonist is pembrolizumab, MEDI-0680 or pidilizumab. 20. The combination of claim 14, wherein said immuno-oncology agent is a PD-L1 antagonist. 21. The combination of claim 20, wherein said PD-L1 antagonist is BMS-936559. 22. The combination of claim 14, wherein said immuno-oncology agent is a LAG-3 antagonist. 23. The combination of claim 22, wherein said LAG-3 antagonist is BMS-986016. 24. The combination of claim 9, wherein said additional therapeutic agent is tremelimumab, MPDL3280A, durvalumab, MSB0010718C, IMP-731, IMP-321, urelumab, PF-05082566, BMS-986153, BMS-986156, TRX-518, MK-4166, MEDI-6383, MEDI-6469, RG-7888, lucatumumab, dacetuzumab, varlilumab, or MGA271. 25. A combination comprising (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00290## or a pharmaceutically acceptable salt thereof, and at least one immuno-oncology agent and at least one chemotherapeutic agent. 26. The combination of claim 25, wherein said immuno-oncology agent is nivolumab. 27. A method of treating melanoma, lung cancer, head cancer, neck cancer, renal cell carcinoma, or bladder cancer in a human in need of such treatment, comprising administering to the human an effective amount of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00291## or a pharmaceutically acceptable salt thereof. 28. A method of treating melanoma, lung cancer, head cancer, neck cancer, renal cell carcinoma, or bladder cancer in a human in need of such treatment, comprising administering to the human an effective amount of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide or a stereoisomer thereof or a pharmaceutically acceptable salt thereof. 29. The method of claim 27, wherein the human is administered (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00292## 30. The method of claim 27, wherein the human is administered a pharmaceutically acceptable salt of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide. 31. The method of claim 27, for treating melanoma. 32. The method of claim 27, for treating lung cancer. 33. The method of claim 27, for treating head cancer. 34. The method of claim 27, for treating neck cancer. 35. The method of claim 27, for treating renal cell carcinoma. 36. The method of claim 27, for treating bladder cancer. 37. The method of claim 27, further comprising administering to said human at least one additional therapeutic agent. 38. The method of claim 28, further comprising administering to said human at least one additional therapeutic agent. 39. The method of claim 29, further comprising administering to said human at least one additional therapeutic agent. 40. The method of claim 30, further comprising administering to said human at least one additional therapeutic agent. 41. The method of claim 37, wherein the at least one additional therapeutic agent is an immuno-oncology agent. 42. The method of claim 41, wherein said immuno-oncology agent is selected from a CTLA-4 antagonist, a PD-1 antagonist, a PD-L1 antagonist, a LAG-3 antagonist, a CD137 agonist, a GITR agonist, an OX40 agonist, and OX40L antagonist, a CD40 agonist or antagonist, a CD27 agonist, a BTLA antagonist, a TIM-3 antagonist, an A2aR antagonist, a Killer Inhibitor Receptor antagonist, or a B7H3 antibody. 43. The method of claim 42, wherein said immuno-oncology agent is a CTLA-4 antagonist. 44. The method of claim 43, wherein said CTLA-4 antagonist is ipilimumab. 45. The method of claim 44, for treating melanoma. 46. The method of claim 44, for treating lung cancer. 47. The method of claim 44, for treating head cancer. 48. The method of claim 44, for treating neck cancer. 49. The method of claim 44, for treating renal cell carcinoma. 50. The method of claim 44, for treating bladder cancer. 51. The method of claim 42, wherein said immuno-oncology agent is a PD-1 antagonist. 52. The method of claim 51, wherein said PD-1 antagonist is nivolumab. 53. The method of claim 52, for treating melanoma. 54. The method of claim 52, for treating lung cancer. 55. The method of claim 52, for treating head cancer. 56. The method of claim 52, for treating neck cancer. 57. The method of claim 52, for treating renal cell carcinoma. 58. The method of claim 52, for treating bladder cancer. 59. The method of claim 51, wherein said PD-1 antagonist is pembrolizumab, MEDI-0680 or pidilizumab. 60. The method of claim 42, wherein said immuno-oncology agent is a PD-L1 antagonist. 61. The method of claim 60, wherein said PD-L1 antagonist is BMS-936559. 62. The method of claim 42, wherein said immuno-oncology agent is a LAG-3 antagonist. 63. The method of claim 62, wherein said LAG-3 antagonist is BMS-986016. 64. The method of claim 41, wherein said additional therapeutic agent is tremelimumab, MPDL3280A, durvalumab, MSB0010718C, IMP-731, IMP-321, urelumab, PF-05082566, BMS-986153, BMS-986156, TRX-518, MK-4166, MEDI-6383, MEDI-6469, RG-7888, lucatumumab, dacetuzumab, varlilumab, or MGA271. 65. A method of treating melanoma, lung cancer, head cancer, neck cancer, renal cell carcinoma, or bladder cancer in a human in need of such treatment, comprising administering to said human an effective amount of (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propana- mide ##STR00293## or a pharmaceutically acceptable salt thereof, said method further comprising administering to said human at least one immuno-oncology agent and at least one chemotherapeutic agent. 66. The method of claim 65, wherein said immuno-oncology agent is nivolumab.

Details for Patent 10,106,546

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2034-11-05
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2034-11-05
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2034-11-05
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	12/22/2014		2034-11-05
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	10/04/2017		2034-11-05
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	08/27/2021		2034-11-05