Claims for Patent: 11,951,212

Summary for Patent: 11,951,212

Title:	Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
Abstract:	The present invention features compositions comprising a plurality of therapeutic agents wherein the presence of one therapeutic agent enhances the properties of at least one other therapeutic agent. In one embodiment, the therapeutic agents are cystic fibrosis transmembrane conductance regulators (CFTR) such as a CFTR corrector or CFTR potentiator for the treatment of CFTR mediated diseases such as cystic fibrosis. Methods and kits thereof are also disclosed.
Inventor(s):	Brian Dean Phenix, Laurent Jean-Claude Bagnol, Geoffrey Glen BRODEUR, Sachin Chandran, Eleni Dokou, Lori Ann Ferris, Dragutin Knezic, Katie Lynn McCarty, Ales Medek, Sara A. Waggener
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US17/204,679
Patent Claims:	1. A pharmaceutical composition comprising a blend of a first solid dispersion and a second solid dispersion, wherein the first solid dispersion comprises 70 wt % to 90 wt % of amorphous (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) relative to the total weight of the first solid dispersion and 10 wt % to 30 wt % of a polymer relative to the total weight of the first solid dispersion, wherein the second solid dispersion comprises 70 wt % to 90 wt % of amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 2) relative to the total weight of the second solid dispersion; and wherein the pharmaceutical composition is a tablet that comprises 25 mg to 125 mg of Compound 1 and 100 mg to 200 mg of Compound 2. 2. The pharmaceutical composition of claim 1, wherein the first solid dispersion comprises 80 wt % of amorphous Compound 1 relative to the total weight of the first solid dispersion and 20 wt % of a polymer relative to the total weight of the first solid dispersion. 3. The pharmaceutical composition of claim 1, wherein the polymer is selected from a water-soluble polymer and a partially water-soluble polymer. 4. The pharmaceutical composition of claim 1, wherein the polymer is selected from cellulose derivatives, polyvinylpyrrolidones (PVP), polyethylene glycols (PEG), polyvinyl alcohols (PVA), acrylates, cyclodextrins, copolymers thereof, and derivatives thereof. 5. The pharmaceutical composition of claim 4, wherein the polymer is a cellulose derivative. 6. The pharmaceutical composition of claim 5, wherein the polymer is selected from hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), and ethylcellulose. 7. The pharmaceutical composition of claim 6, wherein the HPMC is selected from HPMC E50, HPMC E15, and HPMC E3. 8. The pharmaceutical composition of claim 2, wherein the polymer is selected from cellulose acetate phthalate (CAP), hydroxypropyl methyl cellulose phthalates (HPMCP), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), carboxymethylcellulose (CMC), cellulose acetate trimellitate (CAT), hydroxypropylmethyl-cellulose acetate phthalate (HPMCAP), methylcellulose acetate phthalate (MCAP), and polymethacrylates. 9. The pharmaceutical composition according to claim 4, wherein the copolymer is a polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA). 10. The pharmaceutical composition of claim 1, wherein the second solid dispersion further comprises wt % to 30 wt % of a polymer relative to the total weight of the second solid dispersion. 11. The pharmaceutical composition of claim 10, wherein the second solid dispersion comprises 80 wt % of amorphous Compound 2 relative to the total weight of the second solid dispersion, 19.5 wt % of polymer relative to the total weight of the second solid dispersion, and 0.5 wt % of sodium lauryl sulfate relative to the total weight of the second solid dispersion. 12. The pharmaceutical composition of claim 10, wherein the polymer in the second solid dispersion is selected from cellulose derivatives, polyvinylpyrrolidones (PVP), polyethylene glycols (PEG), polyvinyl alcohols (PVA), acrylates, cyclodextrins, copolymers thereof, and derivatives thereof. 13. The pharmaceutical composition of claim 12, wherein the polymer in the second solid dispersion is a cellulose derivative. 14. The pharmaceutical composition of claim 13, wherein the polymer in the second solid dispersion is hydroxypropyl methylcellulose acetate succinate (HPMCAS). 15. The pharmaceutical composition of claim 14, wherein the HPMCAS is hydroxypropyl methyl cellulose acetate succinate HG (HPMCAS-HG). 16. The pharmaceutical composition of claim 1, wherein the tablet comprises 100 mg of Compound 1. 17. The pharmaceutical composition of claim 1, wherein the tablet comprises 150 mg of Compound 2. 18. The pharmaceutical composition of claim 1, wherein the tablet comprises one or more excipients selected from a filler, a disintegrant, and a lubricant, or any combination thereof. 19. The pharmaceutical composition of claim 18, wherein the tablet comprises a filler in an amount of 30 wt % to 50 wt % relative to the total weight of the tablet. 20. The pharmaceutical composition of claim 19, wherein the tablet comprises 100 mg to 300 mg of a filler. 21. The pharmaceutical composition of claim 20, wherein the filler is microcrystalline cellulose. 22. The pharmaceutical composition of claim 18, wherein the tablet comprises a disintegrant in an amount of 1 wt % to 10 wt % relative to the total weight of the tablet. 23. The pharmaceutical composition of claim 22, wherein the tablet comprises 12 mg to 36 mg of a disintegrant. 24. The pharmaceutical composition of claim 23, wherein the disintegrant is croscarmellose sodium. 25. The pharmaceutical composition of claim 18, wherein the tablet comprises a lubricant in an amount of 1 wt % relative to the total weight of the tablet. 26. The pharmaceutical composition of claim 25, wherein the tablet comprises 5.9 mg of a lubricant. 27. The pharmaceutical composition of claim 26, wherein the lubricant is magnesium stearate. 28. The pharmaceutical composition of claim 1, wherein the tablet comprises: 125 mg of a first solid dispersion which comprises 80 wt % of amorphous Compound 1 relative to the total weight of the first solid dispersion and 20 wt % of polymer relative to the total weight of the first solid dispersion, 187.5 mg of a second solid dispersion which comprises 80 wt % of amorphous Compound 2 relative to the total weight of the second solid dispersion, 19.5 wt % of polymer relative to the total weight of the second solid dispersion, and 0.5 wt % of sodium lauryl sulfate relative to the total weight of the second solid dispersion, 30 wt % to 50 wt % filler, 1 wt % to 10 wt % disintegrant, and 1 wt % lubricant. 29. The pharmaceutical composition of claim 18, wherein the filler is microcrystalline cellulose, the disintegrant is croscarmellose sodium, and the lubricant is magnesium stearate. 30. A method of treating cystic fibrosis in a patient comprising orally administering to the patient the pharmaceutical composition of claim 1. 31. The method of claim 30, wherein the pharmaceutical composition is administered once per day. 32. The method of claim 30, wherein the pharmaceutical composition is administered once per day followed by the administration of 150 mg of Compound 2 once per day. 33. The method of claim 30, wherein the patient is heterozygous for a ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation and a second CFTR gene mutation. 34. The method of claim 30, wherein the patient is homozygous for the ΔF508 CFTR gene mutation. 35. A method of treating cystic fibrosis in a patient comprising orally administering to the patient a tablet comprising: a first solid dispersion which comprises 80 wt % of amorphous Compound 1 relative to the total weight of the first solid dispersion and 20 wt % of polymer relative to the total weight of the first solid dispersion, a second solid dispersion which comprises 80 wt % of amorphous Compound 2 relative to the total weight of the second solid dispersion, 19.5 wt % of polymer relative to the total weight of the second solid dispersion, and 0.5 wt % of sodium lauryl sulfate relative to the total weight of the second solid dispersion, and wherein the tablet comprises 100 mg of Compound 1 and 150 mg of Compound 2. 36. The method of claim 35, wherein the polymer of the first solid dispersion and the polymer of the second solid dispersion are selected from cellulose derivatives, polyvinylpyrrolidones (PVP), polyethylene glycols (PEG), polyvinyl alcohols (PVA), acrylates, cyclodextrins, copolymers thereof, and derivatives thereof. 37. The method of claim 36, wherein the polymer of the first solid dispersion and the polymer of the second solid dispersion are independently selected from cellulose derivatives.