Claims for Patent: RE50189

Summary for Patent: RE50189

Title:	Long term treatment of HIV-infection with TMC278
Abstract:	This invention relates to the use of a parenteral formulation comprising an anti-virally effective amount of TMC278 or a pharmaceutically acceptable acid-addition salt thereof, and a carrier, for the manufacture of a medicament for the treatment of a subject being infected with HIV, wherein the formulation is to be administered intermittently at a time interval of at least one week.
Inventor(s):	Lieven Elvire Colette Baert, Guenter Kraus, Gerben Albert Eleutherius van 't Klooster
Assignee:	Janssen Sciences Ireland ULC
Application Number:	US17/473,424
Patent Claims:	1. A method of treating HIV infection in a subject comprising administering to the subject a solution an aqueous parenteral formulation comprising an amount of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (TMC278) or a pharmaceutically acceptable acid-addition salt thereof, and a carrier, wherein the solution aqueous parenteral formulation is administered intermittently by subcutaneous or intramuscular administration at a time interval that is once every one month or once every four weeks, and wherein the amount of TMC278, or the pharmaceutically acceptable acid-addition salt thereof, is effective in keeping a minimum blood plasma level of TMC278 in the subject during the time interval, and the minimum blood plasma level is about 5 ng/mL to about 500 ng/mL. 2. The method according to claim 1, wherein the solution aqueous parenteral formulation is administered intramuscularly. 3. The method according to claim 1, wherein the minimum blood plasma level is about 5 ng/mL to about 500 ng/mL. 4. The method according to claim 1, wherein the minimum blood plasma level is about 5 ng/mL to about 200 ng/mL. 5. The method according to claim 1, wherein the minimum blood plasma level is about 5 ng/mL to about 100 ng/mL. 6. The method according to claim 1, wherein the minimum blood plasma level is about 10 ng/mL to about 50 ng/mL. 7. The method according to claim 1, wherein the subject's HIV viral load is below about 200 copies/mL, prior to administration of the solution aqueous parenteral formulation. 8. The method according to claim 1, wherein the solution is an aqueous solution amount of TMC278, or the pharmaceutically acceptable acid addition salt thereof, constitutes a dose calculated on a basis of about 0.5 mg/day to about 50 mg/day of the time interval. 9. The method according to claim 1, wherein the time interval is once every four weeks. 10. The method according to claim 1, wherein the time interval is once every one month. 11. The method according to claim 1, wherein the TMC278 or the pharmaceutically acceptable acid-addition salt thereof is E-TMC278. 12. The method according to claim 1, wherein the carrier comprises polyethyleneglycol. 13. The method according to claim 8, wherein the carrier comprises polyethyleneglycol. 14. The method according to claim 1, wherein the subject's HIV viral load is below 50 copies/ml, prior to administration of the aqueous parenteral formulation. 15. The method according to claim 2, wherein the TMC278 or the pharmaceutically acceptable acid-addition salt thereof is TMC278. 16. The method according to claim 2, wherein the TMC278 or the pharmaceutically acceptable acid-addition salt thereof is E-TMC278. 17. The method according to claim 8, wherein the aqueous parenteral formulation is administered intramuscularly. 18. The method according to claim 17, wherein the TMC278 or a pharmaceutically acceptable acid-addition salt thereof is E-TMC278. 19. The method according to claim 18, wherein the amount of E-TMC278 is a dose calculated on a basis of about 20 mg/day of the time interval. 20. The method according to claim 18, wherein the amount of E-TMC278 is about 600 mg. 21. The method according to claim 16, wherein the time interval is once every month. 22. The method according to claim 18, wherein the time interval is once every month. 23. The method according to claim 19, wherein the time interval is once every month. 24. The method according to claim 20, wherein the time interval is once every month. 25. The method according to claim 21, wherein the intramuscular administration is administered via a single administration. 26. The method according to claim 22, wherein the intramuscular administration is administered via a single administration. 27. The method according to claim 23, wherein the intramuscular administration is administered via a single administration. 28. The method according to claim 24, wherein the intramuscular administration is administered via a single administration. 29. The method according to claim 25, wherein blood plasma levels of E-TMC278 approach a steady state mode during a prolonged period of time. 30. The method according to claim 26, wherein blood plasma levels of E-TMC278 approach a steady state mode during a prolonged period of time. 31. The method according to claim 27, wherein blood plasma levels of E-TMC278 approach a steady state mode during a prolonged period of time. 32. The method according to claim 28, wherein blood plasma levels of E-TMC278 approach a steady state mode during a prolonged period of time. 33. The method according to claim 27, wherein the E-TMC278 is suspended in the aqueous parenteral formulation. 34. The method according to claim 28, wherein the E-TMC278 is suspended in the aqueous parenteral formulation. 35. The method according to claim 18, wherein the minimum blood plasma level is above 13.5 ng/mL. 36. The method according to claim 23, wherein the minimum blood plasma level is above 13.5 ng/mL. 37. The method according to claim 24, wherein the minimum blood plasma level is above 13.5 ng/mL. 38. The method according to claim 27, wherein the minimum blood plasma level is above 13.5 ng/mL. 39. The method according to claim 28, wherein the minimum blood plasma level is above 13.5 ng/mL. 40. The method according to claim 18, wherein the aqueous parenteral formulation further comprises poloxamer 338. 41. The method according to claim 40, wherein the minimum blood plasma level is above 13.5 ng/mL. 42. The method according to claim 41, wherein the intramuscular administration is administered via a single administration. 43. The method according to claim 18, wherein the time interval is once every four weeks. 44. The method according to claim 43, wherein the minimum blood plasma level is above 13.5 ng/mL. 45. The method according to claim 44, wherein the intramuscular administration is administered via a single administration. 46. A method of treating HIV infection in a subject comprising administering to the subject an aqueous parenteral formulation comprising an amount of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (TMC278) and a carrier, wherein the aqueous parenteral formulation is administered intermittently by intramuscular administration at a time interval that is once every two months, and wherein the amount of TMC278 is effective in keeping a minimum blood plasma level of TMC278 in the subject during the time interval, and the minimum blood plasma level is about 5 ng/mL to about 500 ng/mL. 47. The method according to claim 46, wherein the minimum blood plasma level is about 5 ng/mL to about 200 ng/mL. 48. The method according to claim 46, wherein the minimum blood plasma level is about 5 ng/mL to about 100 ng/mL. 49. The method according to claim 46, wherein the minimum blood plasma level is about 10 ng/mL to about 50 ng/mL. 50. The method according to claim 46, wherein the subject's HIV viral load is below about 200 copies/mL, prior to administration of the aqueous parenteral formulation. 51. The method according to claim 46, wherein the subject's HIV viral load is below about 50 copies/mL, prior to administration of the aqueous parenteral formulation. 52. The method according to claim 46, wherein the amount of TMC278 is a dose calculated on a basis of about 0.5 mg/day to about 50 mg/day of the time interval. 53. The method according to claim 46, wherein the amount of the TMC278 is a dose calculated on a basis of about 10 mg/day to about 20 mg/day of the time interval. 54. The method according to claim 46, wherein the TMC278 is E-TMC278. 55. The method according to claim 54, wherein the amount of E-TMC278 is a dose calculated on a basis of about 0.5 mg/day to about 50 mg/day of the time interval. 56. The method according to claim 55, wherein the minimum blood plasma level is above 13.5 ng/mL. 57. The method according to claim 54, wherein the amount of the E-TMC278 is a dose calculated on a basis of about 10 mg/day to about 20 mg/day of the time interval. 58. The method according to claim 54, wherein the intramuscular administration is via a single administration. 59. The method according to claim 58, wherein blood plasma levels of E-TMC278 approach a steady state mode during a prolonged period of time. 60. The method according to claim 55, wherein the aqueous parenteral formulation further comprises poloxamer 338. 61. The method according to claim 60, wherein the minimum blood plasma level is above 13.5 ng/mL. 62. The method according to claim 61, wherein the intramuscular administration is administered via a single administration. 63. The method according to claim 55, wherein the intramuscular administration is administered via a single administration. 64. The method according to claim 63, wherein blood plasma levels of E-TMC278 approach a steady state mode during a prolonged period of time. 65. The method according to claim 63, wherein the E-TMC278 is suspended in the aqueous parenteral formulation.