Claims for Patent: 10,022,352

Summary for Patent: 10,022,352

Title:	Modulators of ATP-binding cassette transporters
Abstract:	Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
Inventor(s):	Hadida Ruah; Sara Sabina (La Jolla, CA), Grootenhuis; Peter Diederik Jan (San Diego, CA), Van Goor; Fredrick F. (San Diego, CA), Zhou; Jinglan (San Diego, CA), Bear; Brian Richard (Carlsbad, CA), Miller; Mark Thomas (San Diego, CA), McCartney; Jason (Cardiff by the Sea, CA), Numa; Mehdi Michel Djamel (San Diego, CA)
Assignee:	Vertex Pharmaceuticals Incorporated (Boston, MA)
Application Number:	15/078,800
Patent Claims:	1. A method of treating cystic fibrosis in a patient in need thereof, comprising administering to said patient an effective amount of a pharmaceutical composition comprising compound (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)cyclopropanecarbox- amide (Compound A) ##STR00851## wherein said patient possesses at least one human cystic fibrosis transmembrane conductance regulator (CFTR) .DELTA.F508 mutation. 2. The method of claim 1, wherein the pharmaceutical composition further comprises a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. 3. The method of claim 2, wherein the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator is N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide. 4. The method of claim 1, wherein the patient possesses a cystic fibrosis transmembrane conductance regulator (CFTR) with a .DELTA.F508 mutation on both alleles. 5. The method of claim 1, wherein the pharmaceutical composition is in solid dosage form. 6. A method of treating cystic fibrosis in a patient in need thereof, comprising the step of administering to said patient an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable salt of compound (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)cyclopropanecarbox- amide (Compound A) ##STR00852## wherein said patient possesses at least one human cystic fibrosis transmembrane conductance regulator (CFTR) .DELTA.F508 mutation. 7. The method of claim 6, wherein the pharmaceutical composition further comprises a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. 8. The method of claim 7, wherein the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator is N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide. 9. The method of claim 6, wherein the patient possesses a cystic fibrosis transmembrane conductance regulator (CFTR) with a .DELTA.F508 mutation on both alleles. 10. The method of claim 6, wherein the pharmaceutical composition is in solid dosage form. 11. A solid dosage form comprising (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)cyclopropanecarbox- amide (Compound A). 12. The solid dosage form of claim 11, which is a tablet. 13. The solid dosage form of claim 11, further comprising at least one excipient chosen from fillers, lubricants, opacifying agents, and buffering agents. 14. The solid dosage form of claim 12, wherein the tablet further comprises a film coat. 15. A solid dosage form comprising a pharmaceutically acceptable salt of (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)cyclopropanecarbox- amide (Compound A). 16. The solid dosage form of claim 15, which is a tablet. 17. The solid dosage form of claim 15, further comprising at least one excipient chosen from fillers, lubricants, opacifying agents, and buffering agents. 18. The solid dosage form of claim 16, wherein the tablet further comprises a film coat. 19. The solid dosage form of claim 12, further comprising at least one excipient chosen from fillers, lubricants, opacifying agents, and buffering agents. 20. The solid dosage form of claim 16, further comprising at least one excipient chosen from fillers, lubricants, opacifying agents, and buffering agents.