Claims for Patent: 11,564,916

Summary for Patent: 11,564,916

Title:	Pharmaceutical composition and administrations thereof
Abstract:	The present invention relates to pharmaceutical compositions comprising a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, methods of manufacturing pharmaceutical compositions of the present invention, and methods of administering pharmaceutical compositions of the present invention.
Inventor(s):	William Rowe, Patricia Hurter, Christopher Young, Kirk Dinehart, Marinus Jacobus Verwijs, Kirk Overhoff, Peter D. J. Grootenhuis, Martyn Botfield, Alfredo Grossi
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US16/842,480
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,564,916
Patent Claims:	1. A method of treating or lessening the severity of cystic fibrosis (CF) in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a solid dispersion, wherein the solid dispersion comprises: a) 80% of amorphous or substantially amorphous N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1, b) 19.5% of hydroxypropylmethylcellulose acetate succinate (HPMCAS) by weight of the dispersion, and c) 0.5% of sodium lauryl sulfate (SLS) by weight of the dispersion. 2. The method of claim 1, wherein the pharmaceutical composition further comprises 30.5% of microcrystalline cellulose by weight of the composition. 3. The method of claim 1, wherein the pharmaceutical composition further comprises 30.4% of lactose by weight of the composition. 4. The method of claim 1, wherein the pharmaceutical composition further comprises 3% of sodium croscarmellose by weight of the composition. 5. The method of claim 1, wherein the pharmaceutical composition further comprises 0.5% of SLS by weight of the composition. 6. The method of claim 1, wherein the pharmaceutical composition further comprises 0.5% of colloidal silicon dioxide by weight of the composition. 7. The method of claim 1, wherein the pharmaceutical composition further comprises 1.0% of magnesium stearate by weight of the composition. 8. The method of claim 1, wherein the pharmaceutical composition comprises 34.1% of the solid dispersion by weight of the composition. 9. The method of claim 1, wherein substantially amorphous Compound 1 comprises less than 5% crystalline Compound 1. 10. The method of claim 1, wherein the pharmaceutical composition is formulated as a tablet. 11. The method of claim 1, wherein the pharmaceutical composition further comprises a coating. 12. The method of claim 1, wherein the pharmaceutical composition has a hardness of 98 N or 10 kp±20 percent. 13. The method of claim 1, wherein the pharmaceutical composition contains 150 mg of Compound 1. 14. The method of claim 1, wherein the pharmaceutical composition contains 100 mg of Compound 1. 15. The method of claim 1, wherein the pharmaceutical composition is orally administered to the patient twice per day. 16. The method of claim 1, wherein the pharmaceutical composition is orally administered every 12 hours. 17. The method of claim 1, wherein the pharmaceutical composition is orally administered to the patient once per day. 18. The method of claim 1, wherein the pharmaceutical composition is orally administered concurrently with a high fat, high calorie CF meal or snack. 19. The method of claim 1, wherein the pharmaceutical composition is orally administered 30 minutes after administering a high fat, high calorie CF meal or snack. 20. The method of claim 1, wherein the pharmaceutical composition is administered concurrently with, prior to, or subsequent to an additional therapeutic agent. 21. The method of claim 20, wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodilator, an anti-biotic, an anti-infective agent, an anti-inflammatory agent, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator other than Compound 1 or a nutritional agent. 22. The method of claim 21, wherein the additional therapeutic agent is a CFTR modulator other than Compound 1. 23. The method of claim 22, wherein the CFTR modulator other than Compound 1 is (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid. 24. A method of treating or lessening the severity of cystic fibrosis in a patient in need thereof, comprising administering to the patient a pharmaceutical tablet comprising: a. a solid dispersion in an amount ranging from 30% to 50% by weight of the tablet, wherein the dispersion comprises: i) 80% of amorphous or substantially amorphous N-[2,4-Bis(1, 1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1, ii) 19.5% of hydroxypropylmethyl cellulose acetate succinate (HPMCAS) by weight of the dispersion, and iii) 0.5% of sodium lauryl sulfate (SLS) by weight of the dispersion; b. a filler, in an amount ranging from 25% to 50% by weight of the tablet; c. a disintegrant, in an amount ranging from 1% to 10% by weight of the tablet; d. a surfactant, in an amount ranging from 0.3% to 2% by weight of the tablet; e. a binder, in an amount ranging from 20% to 45% by weight of the tablet; f. a glidant, in an amount ranging from 0.09% to 1.0% by weight of the tablet; and g. a lubricant, in an amount ranging from 0.1% to 2% by weight of the tablet. 25. The method of claim 24, wherein substantially amorphous Compound 1 comprises less than 5% crystalline Compound 1. 26. The method of claim 24, wherein the tablet is orally administered to the patient twice per day. 27. The method of claim 24, wherein the tablet is orally administered every 12 hours. 28. The method of claim 24, wherein the tablet is orally administered to the patient once per day. 29. The method of claim 24, wherein the tablet is orally administered concurrently with a high fat, high calorie CF meal or snack. 30. The method of claim 24, wherein the tablet is orally administered 30 minutes after administering a high fat, high calorie CF meal or snack. 31. The method of claim 24, wherein the tablet is administered concurrently with, prior to, or subsequent to an additional therapeutic agent. 32. The method of claim 31, wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodilator, an anti-biotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator other than Compound 1 of the present invention, or a nutritional agent. 33. The method of claim 32, wherein the additional therapeutic agent is a CFTR modulator other than Compound 1. 34. The method of claim 33, wherein the CFTR modulator other than Compound 1 is (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid. 35. A method of treating or lessening the severity of cystic fibrosis in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising: a. 34.1 wt % of a solid dispersion comprising: i) 80% of amorphous or substantially amorphous Compound 1 by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1, ii) 19.5% of HPMCAS by weight of the dispersion, and iii) 0.5% of SLS by weight of the dispersion; b. 30.5% of microcrystalline cellulose by weight of the composition; c. 30.4% of lactose by weight of the composition; d. 3% of sodium croscarmellose by weight of the composition; e. 0.5% of SLS by weight of the composition; f. 0.5% of colloidal silicon dioxide by weight of the composition; and g. 1.0% of magnesium stearate by weight of the composition. 36. The method of claim 35, wherein substantially amorphous Compound 1 comprises less than 5% crystalline Compound 1. 37. The method of claim 35, wherein the pharmaceutical composition is administered concurrently with, prior to, or subsequent to an additional therapeutic agent. 38. The method of claim 37, wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodilator, an anti-biotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator other than Compound 1 of the present invention, or a nutritional agent. 39. The method of claim 38, wherein the additional therapeutic agent is a CFTR modulator other than Compound 1. 40. The method of claim 39, wherein the CFTR modulator other than Compound 1 is (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid.