Prevention of HIV-infection

Patent metadata

Field	Value
Publication number	US-10765674-B2
Application number	US-201615180391-A
Country	US
Kind code	B2
Filing date	Jun 13, 2016
Priority date	Apr 4, 2005
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

This invention relates to the use of a parenteral formulation comprising the NNRTI TMC278 for the long term prevention of HIV infection in a subject at risk of being infected by HIV, which comprises the intermittent administration of the said formulation at long time intervals.

First claim

The invention claimed is:

1. A method of maintaining a blood plasma level of 4-1000 ng/ml of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof in an individual at risk of being infected with HIV-1, comprising
subcutaneously or intramuscularly injecting a solution into the individual, intermittently at a time interval of at least one week, wherein said solution comprises:
sterile water;
a solubilizer or a surfactant; and
a dose, calculated on a basis of 0.2 mg/day to 50 mg/day of the time interval, of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof; or a pharmaceutically acceptable acid-addition salt thereof;
wherein the blood plasma level is maintained over the time interval.

2. The method according to claim 1 wherein the administration time interval is once every 3, 4, 6, 7, or 8 weeks.

3. The method according to claim 1 wherein the administration time interval is once every 1, 2, or 3 months.

4. The method according to claim 1 wherein the administration time interval is once every month.

5. The method according to claim 1 wherein the administration time interval is once every three months.

6. The method according to claim 1 wherein the blood plasma level of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof is maintained over the time interval at a level equal to or above 15 ng/ml.

7. The method according to claim 1 wherein the blood plasma level of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof is maintained over the time interval at a level equal to or above 20 ng/ml.

8. The method according to claim 1 wherein the blood plasma level of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof is maintained over the time interval at a level equal to or above 40 ng/ml.

9. The method according to claim 1 wherein the blood plasma level of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof is maintained over the time interval at a level below 40 ng/ml and above 4 ng/ml.

10. The method according to claim 1 wherein the solubilizer is a cyclodextrin or a cyclodextrin derivative or a polyethylene glycol.

11. The method according to claim 1 , wherein the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof; or a pharmaceutically acceptable acid-addition salt thereof is in base-form.

12. The method according to claim 1 wherein the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile occurs in its E-isomeric form.

13. The method according to claim 11 wherein the base form of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, occurs in its E-isomeric form.

14. The method according to claim 1 wherein the administration time interval is once every two months.

15. The method according to claim 3 wherein the time interval is 30 days and the dose of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof, ranges from 15 mg to 1,500 mg.

16. The method according to claim 3 wherein the time interval is 28 days and the dose of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof, ranges from 14 mg to 1,400 mg.

17. The method according to claim 1 wherein the dose is calculated on a basis of 1 mg/day to 10 mg/day.

18. The method according to claim 3 , wherein the time interval is 29 days and the dose of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof, ranges from 14.5 mg to 1,450 mg.

19. The method according to claim 3 , wherein the time interval is 31 days and the dose of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof, ranges from 15.5 mg to 1,550 mg.

20. The method according to claim 3 , wherein the time interval is about one month and the dose of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino]benzonitrile, the E isomeric form thereof or the Z-isomeric form thereof, ranges from about 15 mg to about 1,500 mg.

21. The method according to claim 3 , wherein the dose is about 30 mg to about 300 mg.

22. The method according to claim 3 , wherein the dose is about 60 mg to about 150 mg.

23. The method according to claim 1 wherein the administration time interval is once every 4 weeks.

24. The method according to claim 1 wherein the administration time interval is once every 8 weeks.

Assignees

• Janssen Sciences Ireland Unlimited Co

Inventors

• Baert Lieven Elvire Colette
• Lewi Paulus Joannes
• Heeres Jan

Classifications

• A61K47/16

  containing nitrogen, {e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates} · CPC title

• A61K31/505 Primary

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title