P
USRE50189EExpiredUtilityPatentIndex 59

Long term treatment of HIV-infection with TMC278

Assignee: JANSSEN SCIENCES IRELAND UNLIMITED COPriority: Jan 20, 2006Filed: Jan 19, 2007Granted: Oct 29, 2024
Est. expiryJan 20, 2026(expired)· nominal 20-yr term from priority
Inventors:BAERT LIEVEN ELVIRE COLETTEKRAUS GUENTERVAN 'T KLOOSTER GERBEN ALBERT ELEUTHERIUS
A61P 31/18A61P 31/00A61K 31/505
59
PatentIndex Score
0
Cited by
81
References
65
Claims

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.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       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.

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