Claims for Patent: 11,807,625

Summary for Patent: 11,807,625

Title:	Capsid inhibitors for the prevention of HIV
Abstract:	The present disclosure provides methods of preventing HIV in a subject, comprising administering to the subject a therapeutically effective amount of a compounds of Formula (Ia) or (Ib):or a pharmaceutically acceptable salt thereof, optionally in combination with one or more additional therapeutic agents. Methods of reducing the risk of acquiring HIV (e.g., HIV-1 and/or HIV-2) are also provided.
Inventor(s):	Elena Bekerman, Wade S. Blair, Anna Chiu, Tomas Cihlar, Dana J. Levine, Winston C. Tse, Stephen R. Yant, Jim X. Zheng
Assignee:	Gilead Sciences Inc
Application Number:	US17/104,554
Patent Claims:	1. A method of preventing an HIV infection in a subject, comprising administering to the subject a compound of Formula (Ia) or Formula (Ib): or a pharmaceutically acceptable salt thereof, wherein: the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 309 mg/mL; or the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 400 mg/mL to about 500 mg/mL; or the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 400 mg/mL; or the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 500 mg/mL. 2. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 309 mg/mL. 3. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 400 mg/mL to about 500 mg/mL. 4. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 400 mg/mL. 5. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered in a dosage of about 2000 mg or about 2500 mg. 6. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 500 mg/mL. 7. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered as a monotherapy. 8. The method of claim 1, wherein the method comprises event driven administration of the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, to the subject. 9. The method of claim 1, wherein the method comprises pre-exposure prophylaxis (PrEP). 10. The method of claim 1, wherein the method comprises post-exposure prophylaxis (PEP). 11. The method of claim 1, wherein the method comprises pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). 12. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered before exposure of the subject to the HIV. 13. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered once from about 14 days to about one day before exposure of the subject to the HIV. 14. The method of claim 1, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered once from about 72 hours to about 1 hour before exposure of the subject to the HIV. 15. The method of claim 9, wherein the pre-exposure prophylaxis (PrEP) comprises continuous PrEP. 16. The method of claim 15, wherein the continuous PrEP comprises daily administration of the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, from about 14 days to about 1 hour before the exposure of the subject to the HIV. 17. The method of claim 1, comprising administering the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, during the period of exposure of the subject to the HIV. 18. The method of claim 17, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered once about every 7 days, about every 14 days, about every 21 days, about every 28 days, about every 35 days, or about every 42 days during the period of exposure of the subject to the HIV. 19. The method of claim 17, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered once about every month, about every 2 months, about every 3 months, about every 6 months, or about every 12 months during the period of exposure of the subject to the HIV. 20. The method of claim 1, comprising administering the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, after final exposure of the subject to the HIV. 21. The method of claim 20, wherein the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered once from about 1 hour to about 14 days after final exposure of the subject to the HIV. 22. The method of claim 1, wherein the method comprises: (i) administering the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, at about 7 days prior to exposure of the subject to the HIV; and (ii) administering the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, once every 7 days, once every 14 days, once every 21 days, once every 28 days, once every 35 days, or once every 42 days, during the period of exposure to the HIV. 23. The method of claim 1, wherein the method comprises: (i) administering the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, at about 7 days prior to exposure of the subject to the HIV; and (ii) administering the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically salt thereof, once every 1 month, once every 2 months, once every 3 months, once every 6 months, or once every 12 months during the period of exposure to the HIV. 24. A method of reducing the risk of acquiring HIV in a subject, comprising administering to the subject a compound of Formula (Ia) or Formula (Ib): or a pharmaceutically acceptable salt thereof, wherein: the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 309 mg/mL, or the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 400 mg/mL to about 500 mg/mL; or the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 400 mg/mL; or the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 500 mg/mL. 25. The method of claim 24, wherein the reduction in risk of acquiring HIV is at least about 75% compared to a subject having not been administered the compound of Formula (Ia) or Formula (Ib), or a pharmaceutically acceptable salt thereof. 26. The method of claim 1, wherein the subject has been identified as an individual who is at risk of sexual transmission of HIV. 27. The method of claim 1, wherein the HIV is HIV-1 or HIV-2. 28. The method of claim 1, wherein the method comprises administering the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof. 29. The method of claim 28, wherein the pharmaceutically acceptable salt of the compound of Formula (Ia) is a sodium salt. 30. The method of claim 1, wherein a solution of the sodium salt of the compound of Formula (Ia) is administered subcutaneously and wherein the solution comprises about 20 w/w % to about 30 w/w % water, about 48 w/w % to about 60 w/w % PEG 300, and about 11 w/w % to about 28 w/w % of a sodium salt of the compound of Formula (Ia). 31. The method of claim 30, wherein a solution of the sodium salt of the compound of Formula (Ia) is administered subcutaneously and wherein the solution comprises about 23.41 w/w % water, about 50.13 w/w % PEG 300, and about 26.46 w/w % of the sodium salt of the compound of Formula (Ia). 32. The method of claim 1, wherein the subject is a human. 33. The method of claim 1, wherein the method comprises administering the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, once every six months. 34. The method of claim 33, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered subcutaneously once every six months as two administrations, each at a concentration of about 309 mg/mL. 35. The method of claim 1, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered intramuscularly once every year. 36. The method of claim 35, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered intramuscularly once every year as two administrations, each at a concentration of about 400 mg/mL to about 500 mg/mL. 37. The method of claim 24, wherein the method comprises administering the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, once every six months. 38. The method of claim 37, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered subcutaneously once every six months as two administrations, each at a concentration of about 309 mg/mL. 39. The method of claim 24, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered intramuscularly once every year. 40. The method of claim 39, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered intramuscularly once every year as two administrations, each at a concentration of about 400 mg/mL to about 500 mg/mL. 41. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 10 w/w % to about 30 w/w % water, about 35 w/w % to about 65 w/w % PEG 300, and about 5 w/w % to about 45 w/w % of a sodium salt of the compound of Formula (Ia), wherein the pharmaceutical composition is a solution. 42. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 21.13 w/w % water, about 45.25 w/w % PEG 300, and about 33.61 w/w % of the sodium salt of the compound of Formula (Ia), wherein the pharmaceutical composition is a solution. 43. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 10 w/w % to about 20 w/w % water, about 30 w/w % to about 40 w/w % PEG 300, about 37 w/w % to about 45 w/w % of a sodium salt of the compound of Formula (Ia), and about 3 w/w % to about 8 w/w % of ethanol, wherein the pharmaceutical composition is a solution. 44. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 16.93 w/w % water, about 36.22 w/w % PEG 300, about 41.85 w/w % of the sodium salt of the compound of Formula (Ia), and about 5.00% ethanol, wherein the pharmaceutical composition is a solution. 45. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 15 w/w % to about 35 w/w % water, about 35 w/w % to about 75 w/w % PEG 300, about 1 w/w % to about 35 w/w % of a sodium salt of a compound of Formula (Ia), and about 0.3 w/w % to about 8 w/w % of poloxamer 188, wherein the pharmaceutical composition is a solution. 46. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 20.16 w/w % water, about 43.17 w/w % PEG 300, about 33.61 w/w % of a sodium salt of a compound of Formula (Ia), and about 3.06 w/w % of poloxamer 188, wherein the pharmaceutical composition is a solution. 47. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 19.18 w/w % water, about 41.09 w/w % PEG 300, about 33.61 w/w % of a sodium salt of a compound of Formula (Ia), and about 6.12 w/w % of poloxamer 188, wherein the pharmaceutical composition is a solution. 48. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 10 w/w % to about 40 w/w % water, about 20 w/w % to about 75 w/w % PEG 300, about 10 w/w % to about 70 w/w % of a sodium salt of the compound of Formula (Ia), about 1 w/w % to about 20 w/w % poloxamer 188, and about 1 w/w % to about 10 w/w % of ethanol, wherein the pharmaceutical composition is a solution. 49. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 15.71 w/w % water, about 33.63 w/w % PEG 300, about 41.85 w/w % of the sodium salt of the compound of Formula (Ia), about 5.00% ethanol, about 3.81 w/w % poloxamer 188, wherein the pharmaceutical composition is a solution. 50. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 14.57 w/w % water, about 31.21 w/w % PEG 300, about 41.64 w/w % of a sodium salt of the compound of Formula (Ia), about 7.58 w/w % poloxamer 188, and about 5.00 w/w % ethanol, wherein the pharmaceutical composition is a solution. 51. The method of claim 1, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 14.50 w/w % water, about 31.04 w/w % PEG 300, about 41.85 w/w % of the sodium salt of the compound of Formula (Ia), about 5.00% ethanol, about 7.61 w/w % poloxamer 188, wherein the pharmaceutical composition is a solution. 52. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 10 w/w % to about 30 w/w % water, about 35 w/w % to about 65 w/w % PEG 300, and about 5 w/w % to about 45 w/w % of a sodium salt of the compound of Formula (Ia), wherein the pharmaceutical composition is a solution. 53. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 21.13 w/w % water, about 45.25 w/w % PEG 300, and about 33.61 w/w % of the sodium salt of the compound of Formula (Ia), wherein the pharmaceutical composition is a solution. 54. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 10 w/w % to about 20 w/w % water, about 30 w/w % to about 40 w/w % PEG 300, about 37 w/w % to about 45 w/w % of a sodium salt of the compound of Formula (Ia), and about 3 w/w % to about 8 w/w % of ethanol, wherein the pharmaceutical composition is a solution. 55. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 16.93 w/w % water, about 36.22 w/w % PEG 300, about 41.85 w/w % of the sodium salt of the compound of Formula (Ia), and about 5.00% ethanol, wherein the pharmaceutical composition is a solution. 56. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 15 w/w % to about 35 w/w % water, about 35 w/w % to about 75 w/w % PEG 300, about 1 w/w % to about 35 w/w % of a sodium salt of a compound of Formula (Ia), and about 0.3 w/w % to about 8 w/w % of poloxamer 188, wherein the pharmaceutical composition is a solution. 57. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 20.16 w/w % water, about 43.17 w/w % PEG 300, about 33.61 w/w % of a sodium salt of a compound of Formula (Ia), and about 3.06 w/w % of poloxamer 188, wherein the pharmaceutical composition is a solution. 58. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 19.18 w/w % water, about 41.09 w/w % PEG 300, about 33.61 w/w % of a sodium salt of a compound of Formula (Ia), and about 6.12 w/w % of poloxamer 188, wherein the pharmaceutical composition is a solution. 59. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 10 w/w % to about 40 w/w % water, about 20 w/w % to about 75 w/w % PEG 300, about 10 w/w % to about 70 w/w % of a sodium salt of the compound of Formula (Ia), about 1 w/w % to about 20 w/w % poloxamer 188, and about 1 w/w % to about 10 w/w % of ethanol, wherein the pharmaceutical composition is a solution. 60. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 15.71 w/w % water, about 33.63 w/w % PEG 300, about 41.85 w/w % of the sodium salt of the compound of Formula (Ia), about 5.00% ethanol, about 3.81 w/w % poloxamer 188, wherein the pharmaceutical composition is a solution. 61. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 14.57 w/w % water, about 31.21 w/w % PEG 300, about 41.64 w/w % of a sodium salt of the compound of Formula (Ia), about 7.58 w/w % poloxamer 188, and about 5.00 w/w % ethanol, wherein the pharmaceutical composition is a solution. 62. The method of claim 24, wherein the intramuscular administration comprises administering to the patient a pharmaceutical composition comprising about 14.50 w/w % water, about 31.04 w/w % PEG 300, about 41.85 w/w % of the sodium salt of the compound of Formula (Ia), about 5.00% ethanol, about 7.61 w/w % poloxamer 188, wherein the pharmaceutical composition is a solution. 63. The method of claim 1, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 400 mg/mL. 64. The method of claim 1, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 500 mg/mL. 65. The method of claim 24, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 400 mg/mL. 66. The method of claim 24, wherein the compound of Formula (Ia), or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 500 mg/mL. 67. The method of claim 24, wherein a solution of the sodium salt of the compound of Formula (Ia) is administered subcutaneously and wherein the solution comprises about 20 w/w% to about 30 w/w% water, about 48 w/w% to about 60 w/w% PEG 300, and about 11 w/w% to about 28 w/w% of a sodium salt of the compound of Formula (Ia). 68. The method of claim 67, wherein a solution of the sodium salt of the compound of Formula (Ia) is administered subcutaneously and wherein the solution comprises about 23.41 w/w% water, about 50.13 w/w% PEG 300, and about 26.46 w/w% of the sodium salt of the compound of Formula (Ia). 69. The method of claim 24, wherein the subject is a human.