Claims for Patent: 9,757,406

Summary for Patent: 9,757,406

Title:	Combination formulation of two antiviral compounds
Abstract:	Disclosed are pharmaceutical compositions comprising Compound I, having the formula: ##STR00001## and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.
Inventor(s):	Gorman; Eric (Foster City, CA), Mogalian; Erik (Foster City, CA), Oliyai; Reza (Foster City, CA), Stefanidis; Dimitrios (Mountain View, CA), Wiser; Lauren (San Francisco, CA), Zia; Vahid (Palo Alto, CA)
Assignee:	Gilead Pharmasset LLC (Foster City, CA)
Application Number:	15/282,128
Patent Claims:	1. A pharmaceutical composition comprising: a) from about 1% to about 25% w/w of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound I to copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula: ##STR00018## b) from about 35% to about 45% w/w of substantially crystalline sofosbuvir having the formula: ##STR00019## c) from about 30% to about 40% w/w of microcrystalline cellulose; d) from about 1% to about 5% w/w of croscarmellose sodium; and e) from about 0.5% to about 2.5% w/w of magnesium stearate. 2. The pharmaceutical composition of claim 1, wherein the crystalline sofosbuvir has XRPD 2.theta.-reflections at about: 6.1 and 12.7 .degree.2.theta..+-.0.2. 3. The pharmaceutical composition of claim 1, wherein the crystalline sofosbuvir has XRPD 2.theta.-reflections at about: 6.1, 20.1, and 20.8 .degree.2.theta..+-.0.2. 4. The pharmaceutical composition of claim 1, comprising about 40% w/w of sofosbuvir. 5. The pharmaceutical composition of claim 1, comprising about 20% w/w of the solid dispersion. 6. The pharmaceutical composition of claim 1, comprising about 35.5% w/w of microcrystalline cellulose. 7. The pharmaceutical composition of claim 1, comprising about 3% w/w of croscarmellose sodium. 8. The pharmaceutical composition of claim 1, comprising about 1.5% w/w of magnesium stearate. 9. A pharmaceutical composition comprising: a) about 20% w/w of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound I to copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula: ##STR00020## b) about 40% w/w of substantially crystalline sofosbuvir having the formula: ##STR00021## c) about 35.5% w/w of microcrystalline cellulose; d) about 3% w/w of croscarmellose sodium; and e) about 1.5% w/w of magnesium stearate. 10. The pharmaceutical composition of claim 9, wherein the crystalline sofosbuvir has XRPD 2.theta.-reflections at about: 6.1 and 12.7 .degree.2.theta..+-.0.2. 11. The pharmaceutical composition of claim 9, wherein the crystalline sofosbuvir has XRPD 2.theta.-reflections at about: 6.1, 20.1, and 20.8 .degree.2.theta..+-.0.2. 12. A pharmaceutical composition comprising: a) about 200 mg of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound I to copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula: ##STR00022## b) about 400 mg of substantially crystalline sofosbuvir having the formula: ##STR00023## c) about 355 mg of microcrystalline cellulose; d) about 30 mg of croscarmellose sodium; and e) about 15 mg of magnesium stearate. 13. The pharmaceutical composition of claim 12 which is in the form of a tablet comprising a film coating. 14. The tablet of claim 13, wherein the film coating is a polyvinylalcohol-based coating. 15. The pharmaceutical composition of claim 12, wherein the crystalline sofosbuvir has XRPD 2.theta.-reflections at about: 6.1 and 12.7 .degree.2.theta..+-.0.2. 16. The pharmaceutical composition of claim 12, wherein the crystalline sofosbuvir has XRPD 2.theta.-reflections at about: 6.1, 20.1, and 20.8 .degree.2.theta..+-.0.2.