# US 10,765,674 B2 · Prevention of HIV-infection > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,765,674 B2 - Document ID: US10765674B2 - Status: Granted - Kind: B2 - Application number: 15/180,391 - Filed: 2016-06-13 - Published: 2016-10-13 - Granted: 2020-09-08 - Earliest claimed: 2005-04-04 - Assignees: Janssen Sciences Ireland Unlimited Company - Applicants: Janssen Sciences Ireland Unlimited Company - Inventors: Lieven Elvire Colette Baert; Paulus Joannes Lewi; Jan Heeres - Web page: https://patentgrep.com/patent/US10765674B2 ## CPC - A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/16: containing nitrogen, {e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates} - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/18: for HIV - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### Claim 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. ### Claim 2 (depends on 1) The method according to claim 1 wherein the administration time interval is once every 3, 4, 6, 7, or 8 weeks. ### Claim 3 (depends on 1) The method according to claim 1 wherein the administration time interval is once every 1, 2, or 3 months. ### Claim 4 (depends on 1) The method according to claim 1 wherein the administration time interval is once every month. ### Claim 5 (depends on 1) The method according to claim 1 wherein the administration time interval is once every three months. ### Claim 6 (depends on 1) 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. ### Claim 7 (depends on 1) 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. ### Claim 8 (depends on 1) 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. ### Claim 9 (depends on 1) 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. ### Claim 10 (depends on 1) The method according to claim 1 wherein the solubilizer is a cyclodextrin or a cyclodextrin derivative or a polyethylene glycol. ### Claim 11 (depends on 1) 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. ### Claim 12 (depends on 1) 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. ### Claim 13 (depends on 11) 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. ### Claim 14 (depends on 1) The method according to claim 1 wherein the administration time interval is once every two months. ### Claim 15 (depends on 3) 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. ### Claim 16 (depends on 3) 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. ### Claim 17 (depends on 1) The method according to claim 1 wherein the dose is calculated on a basis of 1 mg/day to 10 mg/day. ### Claim 18 (depends on 3) 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. ### Claim 19 (depends on 3) 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. ### Claim 20 (depends on 3) 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. ### Claim 21 (depends on 3) The method according to claim 3, wherein the dose is about 30 mg to about 300 mg. ### Claim 22 (depends on 3) The method according to claim 3, wherein the dose is about 60 mg to about 150 mg. ### Claim 23 (depends on 1) The method according to claim 1 wherein the administration time interval is once every 4 weeks. ### Claim 24 (depends on 1) The method according to claim 1 wherein the administration time interval is once every 8 weeks.