You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 28, 2024

Claims for Patent: 6,417,191


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 6,417,191
Title: Synergistic combinations of zidovudine, 1592U89 and 3TC
Abstract:The present invention relates to therapeutic combinations of (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl)-2-cyclopentene- 1-methanol (1592U89), 3'-azido-3'-deoxythymidine (zidovudine) and (2R,cis)-4-amino-]-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin- 2-one (3TC) (or, alternatively to 3TC, (2R,cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyr imidin-2-one (FTC)) which have anti-HIV activity. The present invention is also concerned with pharmaceutical compositions containing said combinations and their use in the treatment of HIV infections including infections with HIV mutants bearing resistance to nucleoside and/or non-nucleoside inhibitors.
Inventor(s): Barry; David Walter (Chapel Hill, NC), St. Clair; Martha Heider (Rougemont, NC)
Assignee: GlaxoSmithKline (Research Triangle Park, NC)
Application Number:08/930,225
Patent Litigation and PTAB cases: See patent lawsuits and PTAB cases for patent 6,417,191
Patent Claims: 1. A method for the treatment or prevention of the symptoms or effects of an HIV infection in an infected animal which comprises treating said animal with a therapeutically effective amount of a combination comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol or a physiologically functional derivative thereof, zidovudine or a physiologically functional derivative thereof, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a physiologically functional derivative thereof.

2. A method according to claim 1 wherein (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol or a physiologically functional derivative thereof, zidovudine or a physiologically function derivative thereof, and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2- one or a physiologically functional derivative thereof are present in a ratio of 1 to 20:1 to 20:1 to 22 by weight.

3. A method according to claim 2 wherein (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one are present in a ratio of 1 to 10:1 to 10:1 to 5 by weight.

4. A method according to claim 2 wherein (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one are present in a ratio of 1 to 3:1 to 3:1 to 2 by weight.

5. A method according to claim 2 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one is present in an amount from 1 to 1500 mg per unit dosage form.

6. A method according to claim 2 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one is present in an amount from 5 to 1000 mg per unit dosage form.

7. A method according to claim 2 wherein the (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

8. A method according to claim 2 wherein the combination is administered simultaneously.

9. A method according to claim 2 wherein the combination is administered sequentially.

10. A method according to claim 2 wherein the combination is administered as a single combined formulation.

11. A method according to claim 2 in which said animal is a human.

12. A method according to claim 1 wherein the physiologically functional derivative of (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

13. A method according to claim 1 wherein (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-3-2-cyclopentene-1- methanol or a physiologically functional derivative thereof, zidovudine or a physiologically function derivative thereof, and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2- one or a physiologically functional derivative thereof are present in a ratio of 1 to 10:1 to 10:1 to 5 by weight.

14. A method according to claim 1 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol or a physiologically functional derivative thereof, zidovudine or a physiologically function derivative thereof, and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2- one or a physiologically functional derivative thereof is present in an amount from 1 to 1500 mg per unit dosage form.

15. A method according to claim 1 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol or a physiologically functional derivative thereof, zidovudine or a physiologically function derivative thereof, and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2- one or a physiologically functional derivative thereof is present in an amount from 5 to 1000 mg per unit dosage form.

16. A pharmaceutical formulation comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol or a physiologically functional derivative thereof, zidovudine or a physiologically functional derivative thereof, and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2- one or a physiologically functional derivative thereof in association with one or more pharmaceutically acceptable carriers therefor.

17. A formulation according to claim 16 in unit dosage.

18. A formulation according to claim 17 in the form of a tablet or capsule.

19. A pharmaceutical formulation according to claim 16 wherein the physiologically functional derivative of (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

20. A method for the treatment or prevention of the symptoms or effects of an HIV infection in an infected animal which comprises treating said animal with a therapeutically effective amount of a combination comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2- one.

21. A method according to claim 1 wherein the combination is administered simultaneously.

22. A method according to claim 1 wherein the combination is administered sequentially.

23. A method according to claim 1 wherein the combination is administered as a single combined formulation.

24. A method according to claim 1 in which said animal is a human.

25. A method according to claim 20 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one is present in an amount from 1 to 1500 mg per unit dosage form.

26. A method according to claim 20 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one is present in an amount from 5 to 1000 mg per unit dosage form.

27. A method according to claim 20 wherein the combination is administered simultaneously.

28. A method according to claim 20 wherein the combination is administered sequentially.

29. A method according to claim 20 wherein the combination is administered as a single combined formulation.

30. A method according to claim 20 in which said animal is a human.

31. A patient pack comprising at least one active ingredient selected from (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one and an information insert containing directions on the use of all three active ingredients together in combination.

32. A method for the treatment or prevention of the symptoms or effects of an HIV infection in an infected animal which comprises treating said animal with a therapeutically effective amount of a combination comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one.

33. A method according to claim 32 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one are present in an amount from 1 to 1500 mg per unit dosage form.

34. A method according to claim 32 wherein each (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one is present in an amount from 5 to 1000 mg per unit dosage form.

35. A method according to claim 32 wherein the (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

36. A method according to claim 32 wherein the combination is administered simultaneously.

37. A method according to claim 32 wherein the combination is administered sequentially.

38. A method according to claim 32 wherein the combination is administered as a single combined formulation.

39. A method according to claim 32 in which said animal is a human.

40. A method according to claim 32 wherein the (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

41. A pharmaceutical formulation comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one in association with one or more pharmaceutically acceptable carriers therefor.

42. A pharmaceutical formulation according to claim 41 wherein the (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

43. A formulation according to claim 41 in unit dosage form.

44. A formulation according to claim 43 in the form of a tablet or capsule.

45. A pharmaceutical formulation comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol, zidovudine, and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one in a ratio of 1 to 20:1 to 20:1 to 10 by weight, in association with one or more pharmaceutically acceptable carriers therefor.

46. A formulation according to claim 45 in unit dosage form.

47. A formulation according to claim 46 in the form of a tablet or capsule.

48. A pharmaceutical formulation comprising (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol or a physiologically functional derivative thereof and (2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a physiologically functional derivative thereof in association with one or more pharmaceutically acceptable carriers therefor.

49. A pharmaceutical formulation according to claim 48 wherein the physiologically functional derivative of (1S, 4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-me thanol is the succinate salt.

50. A formulation according to claim 48 in unit dosage form.

51. A formulation according to claim 50 in the form of a tablet or capsule.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.