Claims for Patent: 10,272,046

Summary for Patent: 10,272,046

Title:	Pharmaceutical composition and administrations thereof
Abstract:	The present invention relates to pharmaceutical compositions containing a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline- -3-carboxamide including formulations of the solid dispersions into powders, granules and mini-tablets, methods for manufacturing and processing the powders, granules and mini-tablets, and methods for treating cystic fibrosis employing the pharmaceutical composition.
Inventor(s):	Dokou; Eleni (Cambridge, MA), Jamzad; Shahla (Belmont, MA), Caesar, Jr.; John P. (Lancaster, MA), Fawaz; Majed (Foxboro, MA), Das; Laura (Charlestown, MA), Gu; Chong-Hui (Waban, MA), Hurter; Patricia Nell (Harvard, MA), Israni; Meghna Jai (Boston, MA), Johnston; Meghan M. (Wakefield, MA), Knezic; Dragutin (Watertown, MA), Kuzmission; Andrew G. (Shrewsburg, MA), Wang; HongRen (Lexington, MA)
Assignee:	Vertex Pharmaceuticals Incorporated (Boston, MA)
Application Number:	15/181,114
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,272,046
Patent Claims:	1. A pharmaceutical composition in a unit dose form comprising one or a plurality of granules, pellets, particles or mini-tablets, wherein the composition comprises: a solid dispersion in an amount from about 30 to about 50 percent by weight of the composition, wherein the dispersion comprises about 80 wt % of substantially amorphous or amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline- -3-carboxamide (Compound 1) by weight of the dispersion, about 19.5 wt % of HPMCAS by weight of the dispersion, and about 0.5 wt % SLS by weight of the dispersion; mannitol and lactose in an amount from about 30 to about 60 percent by weight of the composition, wherein mannitol and lactose are present in a ratio of about 1:3 mannitol to lactose; sucralose in an amount from about 1.5 to about 2.5 percent by weight of the composition; croscarmellose sodium in an amount from about 4 to about 8 percent by weight of the composition; colloidal silicon dioxide in an amount from about 0.5 to about 1.5 percent by weight of the composition; and magnesium stearate in an amount from about 0.5 to about 1.5 percent by weight of the composition; wherein the composition does not comprise SLS outside the solid dispersion. 2. The pharmaceutical composition of claim 1, wherein the unit dose form comprises from about 1 mg to about 100 mg of substantially amorphous or amorphous Compound 1. 3. The pharmaceutical composition of claim 2, wherein the unit dose form comprises about 50 mg of substantially amorphous or amorphous Compound 1. 4. The pharmaceutical composition of claim 2, wherein the unit dose form comprises about 75 mg of substantially amorphous or amorphous Compound 1. 5. The pharmaceutical composition of claim 2, wherein the unit dose form comprises from about 25 to about 40 mini-tablets. 6. The pharmaceutical composition of claim 5, wherein the mini-tablet has a shape that is cylinder-like, oval-like, cone-like, sphere-like, ellipsis-like, polygon-like or combinations thereof, wherein the mini-tablet has as its longest dimension or diameter a length of about 2 mm. 7. The pharmaceutical composition of claim 2, wherein the solid dispersion is present in an amount of about 35 percent by weight of the pharmaceutical composition and the unit dose form comprises from about 26 mini-tablets. 8. The pharmaceutical composition of claim 7, wherein the unit dose form comprises about 50 mg of substantially amorphous or amorphous Compound 1. 9. The pharmaceutical composition of claim 2, wherein the solid dispersion is present in an amount of about 35 percent by weight of the pharmaceutical composition and the unit dose form comprises about 39 mini-tablets. 10. The pharmaceutical composition of claim 9, wherein the unit dose form comprises about 75 mg of substantially amorphous or amorphous Compound 1. 11. The pharmaceutical composition of any one of claims 1-5, wherein the solid dispersion is present in an amount from about 30 to about 40 percent by weight of the composition. 12. The pharmaceutical composition of any one of claims 1-5, wherein the solid dispersion is present in an amount of about 35 percent by weight of the composition. 13. A method of treating or lessening the severity of CFTR mediated disease in a pediatric patient comprising administering to the patient a pharmaceutical composition of claim 1. 14. The method of claim 13, wherein the CFTR mediated disease is cystic fibrosis, COPD, emphysema, dry-eye disease or osteoporosis. 15. The method of claim 14, wherein the CFTR mediated disease is cystic fibrosis. 16. The method of claim 15, wherein the patient possesses a CFTR gating mutation. 17. The method of claim 16, wherein the gating mutation is selected from G551D, G178R, G551S, G970R, G1244E, S1255P, G1349D, S549N, S549R, and S1251N. 18. The method according to claim 13, wherein the patient is 2 through 5 years of age. 19. The method according to claim 13, wherein the patient is 0 through 2 years of age. 20. The method according to claim 13, wherein the patient weighs 14 or more kilograms. 21. The method according to claim 13, wherein the patient weighs less than 14 kilograms. 22. The method according to claim 13, wherein the solid dispersion is present in an amount from about 30 to about 40 percent by weight of the pharmaceutical composition. 23. The method according to claim 13, wherein the solid dispersion is present in an amount of about 35 percent by weight of the pharmaceutical composition.