Claims for Patent: 10,105,365

Summary for Patent: 10,105,365

Title:	Solid antiviral dosage forms
Abstract:	The present disclosure relates to solid dosage forms comprising antiviral compounds and methods of using such dosage forms to treat antiviral infection.
Inventor(s):	Miller; Jonathan M. (Lindenhurst, IL), Morris; John B. (Grayslake, IL), Sever; Nancy E. (Northbrook, IL), Schmitt; Eric A. (Libertyville, IL), Gao; Ping X. (Highland Park, IL), Shi; Yi (Libertyville, IL), Gao; Yi (Vernon Hills, IL), Liepold; Bernd (Dossenheim, DE), Moosmann; Anna (Winterbach, DE), Pauli; Mirko (Ludwigshafen, DE), Durak; Fatih (Ludwigshafen, DE), Kessler; Thomas (Schifferstadt, DE), Hoelig; Peter (Waechtersbach, DE), Rosenblatt; Karin (Mannheim, DE), Kostelac; Drazen (Mannheim, DE), Gokhale; Rajeev (Singapore, SG), Costello; Mark (Chicago, IL), Knable; Carl (Elmhurst, IL), George; Susan (Waukegan, IL)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	15/639,424
Patent Claims:	1. A solid dosage form comprising: ##STR00011## or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable polymer, or combination of pharmaceutically acceptable polymers, in an amount of 350 mg to 2500 mg. 2. The solid dosage form of claim 1, comprising the pharmaceutically acceptable polymer, or combination of pharmaceutically acceptable polymers in an amount of 500 mg to 1000 mg. 3. The solid dosage form of claim 1, wherein the pharmaceutically acceptable polymer or combination of pharmaceutically acceptable polymers comprises (i) a pharmaceutically acceptable stabilizing polymer, or combination of pharmaceutically acceptable stabilizing polymers; and (ii) a pharmaceutically acceptable release rate-modifying polymer, or combination of pharmaceutically acceptable release rate-modifying polymers; wherein the stabilizing polymer, or combination of stabilizing polymers, and the release rate-modifying polymer, or combination of release rate-modifying polymers, can be the same or different. 4. The solid dosage form of claim 3, wherein the pharmaceutically acceptable stabilizing polymer, or combination of pharmaceutically acceptable stabilizing polymers is selected from the group consisting of copovidone, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and combinations thereof; and the pharmaceutically acceptable release rate-modifying polymer, or combination of pharmaceutically acceptable release rate-modifying polymers are selected from the group consisting of polyvinylpyrolidone, hydroxypropyl methylcellulose, ethylcellulose polymers, copovidone, polyvinyl acetate, methacrylate/methacrylic free acid copolymers, polyethylene glycols, polaxamers, and combinations thereof. 5. The solid dosage form of claim 1, wherein the pharmaceutically acceptable polymer or combination of pharmaceutically acceptable polymers is selected from the group consisting of copovidone, hypromellose, and combinations thereof. 6. The solid dosage form of claim 1, further comprising a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants. 7. The solid dosage form of claim 1, wherein the total weight of the solid dosage form is from 1000 mg to 1600 mg. 8. The solid dosage form of claim 1 comprising a first composition and a second composition. 9. The solid dosage form of claim 8, wherein the first composition comprises Compound 1, Compound 2, and ritonavir, and the second composition comprises Compound 4 or a pharmaceutically acceptable salt thereof. 10. The solid dosage form of claim 9, wherein the second composition further comprises a stabilizing polymer or combination of stabilizing polymers in an amount of 10% to 60% by weight of the second composition. 11. The solid dosage form of claim 9, wherein the second composition comprises a release rate-modifying polymer, or combination of release rate-modifying polymers in an amount of 5% to 60% by weight of the second composition. 12. The solid dosage form of claim 9, wherein the first composition comprises 5% to 10% of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, by total weight of the first composition. 13. The solid dosage form of claim 9, wherein the first composition comprises 70-85% of a pharmaceutically acceptable hydrophilic polymer or a combination of pharmaceutically acceptable hydrophilic polymers. 14. The solid dosage form of claim 13, wherein the pharmaceutically acceptable hydrophilic polymer or combination of pharmaceutically acceptable hydrophilic polymers comprises copovidone. 15. The solid dosage form of claim 1, wherein the pharmaceutically acceptable salt of Compound 4 is an alkali metal salt. 16. The solid dosage form of claim 15, wherein the alkali metal salt of Compound 4 is a sodium monohydrate salt of Compound 4. 17. The solid dosage form of claim 16, comprising 216.2 mg of the sodium monohydrate salt of Compound 4. 18. A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient at least one solid dosage form of claim 1. 19. A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient three solid dosage forms of claim 1. 20. A solid dosage form comprising: ##STR00012## or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable polymer, or combination of pharmaceutically acceptable polymers in an amount of 350 mg to 2500 mg; wherein when a single dose consisting of three of the solid dosage forms is administered to humans under non-fasting conditions, the average AUC.sub..infin. for Compound 1 is from 2,000 nghr/mL to 25,000 nghr/mL, the average AUC.sub..infin. for Compound 2 is from 800 nghr/mL to 2,000 nghr/mL, the average AUC.sub..infin. for ritonavir is from 3,000 nghr/mL to 18,000 nghr/mL, and the average AUC.sub..infin. for Compound 4 is from 4,000 nghr/mL to 30,000 nghr/mL. 21. The solid dosage form of claim 20, wherein when a single dose consisting of three of the solid dosage forms is administered to humans under non-fasting conditions, the average AUC.sub..infin. for Compound 1 is from 2,500 nghr/mL to 15,000 nghr/mL, the average AUC.sub..infin. for Compound 2 is from 1,000 nghr/mL to 2,000 nghr/mL, the average AUC.sub..infin. for ritonavir is from 4,000 nghr/mL to 12,000 nghr/mL, and the average AUC.sub..infin. for Compound 4 is from 6,000 nghr/mL to 20,000 nghr/mL. 22. The solid dosage form of claim 20, wherein when a single dose consisting of three of the solid dosage forms is administered to humans under non-fasting conditions, the average AUC.sub..infin. for Compound 1 is from 4,000 nghr/mL to 5,000 nghr/mL, the average AUC.sub..infin. for Compound 2 is from 1,500 nghr/mL to 2,000 nghr/mL, the average AUC.sub..infin. for ritonavir is from 7,000 nghr/mL to 9,000 nghr/mL, and the average AUC.sub..infin. for Compound 4 is from 10,000 nghr/mL to 20,000 nghr/mL. 23. The solid dosage form of claim 20, comprising the pharmaceutically acceptable polymer, or combination of pharmaceutically acceptable polymers in an amount of 500 mg to 1000 mg. 24. The solid dosage form of claim 20, wherein the pharmaceutically acceptable polymer or combination of pharmaceutically acceptable polymers comprises (i) a pharmaceutically acceptable stabilizing polymer, or combination of pharmaceutically acceptable stabilizing polymers; and (ii) a pharmaceutically acceptable release rate-modifying polymer, or combination of pharmaceutically acceptable release rate-modifying polymers; wherein the stabilizing polymer, or combination of stabilizing polymers, and the release rate-modifying polymer, or combination of release rate-modifying polymers, can be the same or different. 25. The solid dosage form of claim 24, wherein the pharmaceutically acceptable stabilizing polymer, or combination of pharmaceutically acceptable stabilizing polymers is selected from the group consisting of copovidone, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and combinations thereof; and the pharmaceutically acceptable release rate-modifying polymer, or combination of pharmaceutically acceptable release rate-modifying polymers are selected from the group consisting of polyvinylpyrolidone, hydroxypropyl methylcellulose, ethylcellulose polymers, copovidone, polyvinyl acetate, methacrylate/methacrylic free acid copolymers, polyethylene glycols, polaxamers, and combinations thereof. 26. The solid dosage form of claim 20, wherein the pharmaceutically acceptable polymer or combination of pharmaceutically acceptable polymers is selected from the group consisting of copovidone, hypromellose, and combinations thereof. 27. The solid dosage form of claim 20, further comprising a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants. 28. The solid dosage form of claim 20, wherein the total weight of the solid dosage form is from 1000 mg to 1600 mg. 29. The solid dosage form of claim 20 comprising a first composition and a second composition. 30. The solid dosage form of claim 29, wherein the first composition comprises Compound 1, Compound 2, and ritonavir, and the second composition comprises Compound 4 or a pharmaceutically acceptable salt thereof. 31. The solid dosage form of claim 30, wherein the second composition further comprises a stabilizing polymer or combination of stabilizing polymers in an amount of 10% to 60% by weight of the second composition. 32. The solid dosage form of claim 30, wherein the second composition comprises a release rate-modifying polymer, or combination of release rate-modifying polymers in an amount of 5% to 60% by weight of the second composition. 33. The solid dosage form of claim 30, wherein the first composition comprises 5% to 10% of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, by total weight of the first composition. 34. The solid dosage form of claim 30, wherein the first composition comprises 70-85% of a pharmaceutically acceptable hydrophilic polymer or a combination of pharmaceutically acceptable hydrophilic polymers. 35. The solid dosage form of claim 34, wherein the pharmaceutically acceptable hydrophilic polymer or combination of pharmaceutically acceptable hydrophilic polymers comprises copovidone. 36. The solid dosage form of claim 20, wherein the pharmaceutically acceptable salt of Compound 4 is an alkali metal salt. 37. The solid dosage form of claim 36, wherein the alkali metal salt of Compound 4 is a sodium monohydrate salt of Compound 4. 38. The solid dosage form of claim 36, comprising 216.2 mg of the sodium monohydrate salt of Compound 4. 39. A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient at least one solid dosage form of claim 20. 40. A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient three solid dosage forms of claim 20. 41. A solid dosage form comprising: ##STR00013## or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable polymer, or combination of pharmaceutically acceptable polymers in an amount of 350 mg to 2500 mg; wherein when a single dose consisting of three of the solid dosage forms is administered to humans under non-fasting conditions, the average C.sub.max for Compound 1 is from 200 ng/mL to 4,000 ng/mL, the average C.sub.max for Compound 2 is from 50 ng/mL to 200 ng/mL, the average C.sub.max for ritonavir is from 500 ng/mL to 2,500 ng/mL, and the average C.sub.max for Compound 4 is from 400 ng/mL to 2,000 ng/mL. 42. The solid dosage form of claim 41, wherein when a single dose consisting of three of the solid dosage forms is administered to humans under non-fasting conditions, the average C.sub.max for Compound 1 is from 350 ng/mL to 2,200 ng/mL, the average C.sub.max for Compound 2 is from 90 ng/mL to 180 ng/mL, the average C.sub.max for ritonavir is from 700 ng/mL to 2,000 ng/mL, and the average C.sub.max for Compound 4 is from 750 ng/mL to 1,500 ng/mL. 43. The solid dosage form of claim 41, wherein when a single dose consisting of three of the solid dosage forms is administered to humans under non-fasting conditions, the average AUC.sub..infin. for Compound 1 is from 2,000 nghr/mL to 25,000 nghr/mL, the average AUC.sub..infin. for Compound 2 is from 800 nghr/mL to 2,000 nghr/mL, the average AUC.sub..infin. for ritonavir is from 3,000 nghr/mL to 18,000 nghr/mL, and the average AUC.sub..infin. for Compound 4 is from 4,000 nghr/mL to 30,000 nghr/mL. 44. The solid dosage form of claim 41, comprising the pharmaceutically acceptable polymer, or combination of pharmaceutically acceptable polymers in an amount of 500 mg to 1000 mg. 45. The solid dosage form of claim 41, wherein the pharmaceutically acceptable polymer or combination of pharmaceutically acceptable polymers comprises (i) a pharmaceutically acceptable stabilizing polymer, or combination of pharmaceutically acceptable stabilizing polymers; and (ii) a pharmaceutically acceptable release rate-modifying polymer, or combination of pharmaceutically acceptable release rate-modifying polymers; wherein the stabilizing polymer, or combination of stabilizing polymers, and the release rate-modifying polymer, or combination of release rate-modifying polymers, can be the same or different. 46. The solid dosage form of claim 45, wherein the pharmaceutically acceptable stabilizing polymer, or combination of pharmaceutically acceptable stabilizing polymers is selected from the group consisting of copovidone, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and combinations thereof; and the pharmaceutically acceptable release rate-modifying polymer, or combination of pharmaceutically acceptable release rate-modifying polymers are selected from the group consisting of polyvinylpyrolidone, hydroxypropyl methylcellulose, ethylcellulose polymers, copovidone, polyvinyl acetate, methacrylate/methacrylic free acid copolymers, polyethylene glycols, polaxamers, and combinations thereof. 47. The solid dosage form of claim 41, wherein the pharmaceutically acceptable polymer or combination of pharmaceutically acceptable polymers is selected from the group consisting of copovidone, hypromellose, and combinations thereof. 48. The solid dosage form of claim 41, further comprising a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants. 49. The solid dosage form of claim 41, wherein the total weight of the solid dosage form is from 1000 mg to 1600 mg. 50. The solid dosage form of claim 41 comprising a first composition and a second composition. 51. The solid dosage form of claim 50, wherein the first composition comprises Compound 1, Compound 2, and ritonavir, and the second composition comprises Compound 4 or a pharmaceutically acceptable salt thereof. 52. The solid dosage form of claim 50, wherein the second composition further comprises a stabilizing polymer or combination of stabilizing polymers in an amount of 10% to 60% by weight of the second composition. 53. The solid dosage form of claim 50, wherein the second composition comprises a release rate-modifying polymer, or combination of release rate-modifying polymers in an amount of 5% to 60% by weight of the second composition. 54. The solid dosage form of claim 50, wherein the first composition comprises 5% to 10% of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, by total weight of the first composition. 55. The solid dosage form of claim 50, wherein the first composition comprises 70-85% of a pharmaceutically acceptable hydrophilic polymer or a combination of pharmaceutically acceptable hydrophilic polymers. 56. The solid dosage form of claim 55, wherein the pharmaceutically acceptable hydrophilic polymer or combination of pharmaceutically acceptable hydrophilic polymers comprises copovidone. 57. The solid dosage form of claim 41, wherein the pharmaceutically acceptable salt of Compound 4 is an alkali metal salt. 58. The solid dosage form of claim 57, wherein the alkali metal salt of Compound 4 is a sodium monohydrate salt of Compound 4. 59. The solid dosage form of claim 58, comprising 216.2 mg of the sodium monohydrate salt of Compound 4. 60. A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient at least one solid dosage form of claim 41. 61. A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient three solid dosage forms of claim 41.