Claims for Patent: 8,835,407

Summary for Patent: 8,835,407

Title:	Pharmaceutical compositions comprising prasugrel and cyclodextrin derivatives and methods of making and using the same
Abstract:	The present invention is directed to pharmaceutical compositions comprising prasugrel and a cyclodextrin derivative, and methods of making and using the same.
Inventor(s):	Mosher; Gerold L. (Kansas City, MO), Machatha; Stephen G. (Waltham, MA), Cushing; Daniel J. (Phoenixville, PA)
Assignee:	CyDex Pharmaceuticals, Inc. (La Jolla, CA)
Application Number:	13/542,253
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,835,407
Patent Claims:	1. A method of administering prasugrel and its pharmaceutically acceptable salts to a subject suffering from an acute coronary syndrome, comprising: identifying a subject suffering from an acute coronary syndrome; administering to the subject a loading dose of a pharmaceutical composition comprising: prasugrel, and a cyclodextrin derivative of formula I: ##STR00008## wherein: n is 4, 5 or 6, and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from: --OH, a straight-chain or branched --O--(C.sub.1-C.sub.8-(alkylene))-SO.sub.3.sup.- group, an optionally substituted straight-chain, branched, or cyclic --O--(C.sub.1-C.sub.10) group, an optionally substituted straight-chain, branched, or cyclic --S--(C.sub.1-C.sub.10) group, and a saccharide, and wherein the cyclodextrin derivative is present in a concentration of at least 100:1 by weight relative to the prasugrel; and subsequently administering to the subject a maintenance dose of said pharmaceutical composition, wherein the maintenance dose comprises a lower amount of prasugrel than the loading dose. 2. The method of claim 1, wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 is a --O-(hydroxy-substituted-C.sub.3) group. 3. The method of claim 1, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently a straight-chain or branched --O--(C.sub.1-C.sub.8-(alkylene))-SO.sub.3.sup.- group having an average degree of substitution of about 4 to about 8 per cyclodextrin derivative, and the remaining substituents are --OH. 4. The method of claim 3, wherein the straight-chain or branched --O--(C.sub.1-C.sub.8-(alkylene))-SO.sub.3.sup.- group is sulfobutyl ether. 5. The method of claim 3, wherein the average degree of substitution is about 6 to about 8. 6. The method of claim 3, wherein the average degree of substitution is about 6.5 to about 7.5. 7. The method of claim 3, wherein the cyclodextrin derivative is a compound of formula II: ##STR00009## wherein R is selected from (H).sub.21-x or (--(CH.sub..sub.2).sub..sub.4-SO.sub.3.sup.-Na.sup.+).sub.x. 8. The method of claim 7, wherein x is 6.0 to 7.1. 9. The method of claim 3, wherein the loading dose is administered parenterally. 10. The method of claim 9, wherein the loading dose is administered intravenously. 11. The method of claim 10, wherein the loading dose is administered by a bolus injection. 12. The method of claim 3, wherein the maintenance dose is administered parenterally. 13. The method of claim 3, wherein the maintenance dose is administered orally. 14. The method of claim 3, wherein the loading dose comprises from about 20 mg to about 120 mg of prasugrel. 15. The method of claim 3, wherein the loading dose comprises from about 20 mg to about 80 mg of prasugrel. 16. The method of claim 3, wherein the loading dose comprises about 60 mg of prasugrel. 17. The method of claim 3, wherein the maintenance dose comprises from about 1 mg to about 20 mg prasugrel. 18. The method of claim 3, wherein the maintenance dose comprises from about 1 mg to about 10 mg prasugrel. 19. The method of claim 3, wherein the maintenance dose comprises about 10 mg prasugrel. 20. The method of claim 3, wherein the maintenance dose comprises about 5 mg prasugrel. 21. The method of claim 3, wherein the maintenance dose is administered once daily. 22. The method of claim 3, wherein the maintenance dose is administered twice daily. 23. The method of claim 3, further comprising administering a nonsteroidal anti-inflammatory drug. 24. The method of claim 23, wherein the nonsteroidal anti-inflammatory drug is aspirin. 25. A method for inhibiting platelet activation in a patient for which oral administration of prasugrel is contra-indicated, comprising parenterally administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising: prasugrel, and a cyclodextrin derivative of formula I: ##STR00010## wherein: n is 4, 5 or 6, and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from: --OH, a straight-chain or branched --O--(C.sub.1-C.sub.8-(alkylene))-SO.sub.3.sup.- group, an optionally substituted straight-chain, branched, or cyclic --O--(C.sub.1-C.sub.10) group, an optionally substituted straight-chain, branched, or cyclic --S--(C.sub.1-C.sub.10) group, and a saccharide, and wherein the cyclodextrin derivative is present in a concentration of at least 100:1 by weight relative to the prasugrel. 26. The method of claim 25, further comprising administering a second therapeutic agent. 27. The method of claim 26, wherein the second therapeutic agent is selected from streptokinase, alteplase, reteplase, urokinase, tenecteplase, aspirin, bivalirudin, heparin, warfarin, eptifibatide, abciximab, and tirofiban. 28. The method of claim 25, wherein the composition is administered intravenously. 29. The method of claim 28, wherein the composition is administered in a bolus dose. 30. A method of inhibiting platelet activation in a patient in need thereof, comprising, prior to the patient undergoing an invasive procedure, administering to the patient a therapeutically effective amount of prasugrel in a pharmaceutical composition comprising: prasugrel, and a cyclodextrin derivative of formula I: ##STR00011## wherein: n is 4, 5 or 6, and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from: --OH, a straight-chain or branched --O--(C.sub.1-C.sub.8-(alkylene))-SO.sub.3.sup.- group, an optionally substituted straight-chain, branched, or cyclic --O--(C.sub.1-C.sub.10) group, an optionally substituted straight-chain, branched, or cyclic --S--(C.sub.1-C.sub.10) group, and a saccharide, and wherein the cyclodextrin derivative is present in a concentration of at least 100:1 by weight relative to the prasugrel. 31. The method of claim 30, further comprising administering a second therapeutic agent. 32. The method of claim 31, wherein the second therapeutic agent is selected from streptokinase, alteplase, reteplase, urokinase, tenecteplase, aspirin, bivalirudin, heparin, warfarin, eptifibatide, abciximab, and tirofiban. 33. The method of claim 30, wherein the composition is administered intravenously. 34. The method of claim 33, wherein the composition is administered in a bolus dose. 35. A method of preparing a prasugrel composition for parenteral administration, comprising reconstituting a solid prasugrel composition with a pharmaceutically acceptable diluent, wherein the prasugrel composition comprises: prasugrel or its pharmaceutically acceptable salt, and a cyclodextrin derivative of formula I: ##STR00012## wherein: n is 4, 5 or 6, and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from: --OH, a straight-chain or branched --O--(C.sub.1-C.sub.8-(alkylene))-SO.sub.3.sup.- group, an optionally substituted straight-chain, branched, or cyclic --O--(C.sub.1-C.sub.10) group, an optionally substituted straight-chain, branched, or cyclic --S--(C.sub.1-C.sub.10) group, and a saccharide, and wherein the cyclodextrin derivative is present in a concentration of at least 100:1 by weight relative to the prasugrel. 36. The method of claim 35, wherein the pharmaceutically acceptable diluent is sterile water. 37. The method of claim 35, comprising reconstituting the prasugrel composition using from about 10 ml to about 500 ml of the pharmaceutically acceptable diluent. 38. The method of claim 35, further comprising diluting the reconstituted solution.

Details for Patent 8,835,407

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2029-05-13
Genentech, Inc.	ACTIVASE	alteplase	For Injection	103172	11/13/1987		2029-05-13
Genentech, Inc.	CATHFLO ACTIVASE	alteplase	For Injection	103172	09/04/2001		2029-05-13
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2029-05-13
Chiesi Usa, Inc.	RETAVASE	reteplase	For Injection	103786	10/30/1996		2029-05-13
Genentech, Inc.	TNKASE	tenecteplase	For Injection	103909	06/02/2000		2029-05-13