Claims for Patent: 12,065,432

Summary for Patent: 12,065,432

Title:	Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid
Abstract:	The present invention relates to a substantially crystalline and free solid state form of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Form I), pharmaceutical compositions thereof, and methods of treatment therewith.
Inventor(s):	Ali Keshavarz-Shokri, Beili Zhang, Mariusz Krawiec
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US16/783,338
Patent Claims:	1. A method of treating cystic fibrosis in a mammal comprising administering to the mammal an effective amount of 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid, characterized as Form I, and an additional therapeutic agent. 2. The method of claim 1, wherein the additional therapeutic agent is a mucolytic agent, a bronchodialator, an anti-biotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator, or a nutritional agent. 3. The method of claim 1, wherein the mammal has a defective gene that causes a deletion of phenylalanine at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR) amino acid sequence. 4. The method of claim 3, wherein the mammal has two copies of the defective gene. 5. A method of treating cystic fibrosis in a mammal comprising administering to the mammal an effective amount of: (a) 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid, characterized as Form I, wherein the Form I is characterized by one or more peaks within one or more 2θ ranges selected from 15.2 to 15.6, 16.1 to 16.5, and 14.3 to 14.7 degrees in an X-ray powder diffraction pattern obtained using Cu K alpha radiation at 40 kV, 35 mA; and (b) an additional therapeutic agent. 6. The method of claim 5, wherein the Form I is characterized by a peak within the range of 15.2 to 15.6 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 7. The method of claim 6, wherein the Form I is characterized by a peak at 15.4 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 8. The method of claim 5, wherein the Form I is characterized by a peak within the range of 16.1 to 16.5 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 9. The method of claim 8, wherein the Form I is characterized by a peak at 16.3 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 10. The method of claim 5, wherein the Form I is characterized by a peak within the range of 14.3 to 14.7 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 11. The method of claim 10, wherein the Form I is characterized by a peak at 14.5 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 12. The method of claim 5, wherein the Form I is further characterized by a peak within the range of 17.6 to 18.0 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 13. The method of claim 5, wherein Compound 1 Form I is further characterized by a peak within the range of 7.6 to 8.0 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 14. The method of claim 5, wherein the Form I is characterized by one or more peaks having a 2θ value, ±0.2 degrees, selected from 14.41 degrees, 14.64 degrees, 15.23 degrees, 16.11 degrees, 17.67 degrees, 19.32 degrees, 21.67 degrees, 23.40 degrees, 23.99 degrees, 26.10 degrees, and 28.54 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation. 15. The method of claim 5, wherein the Form I is characterized by one or more peaks having a 2θ value, ±0.2 degrees, selected from 7.83 degrees, 14.51 degrees, 14.78 degrees, 15.39 degrees, 16.26 degrees, 16.62 degrees, 17.81 degrees, 21.59 degrees, 23.32 degrees, 24.93 degrees, and 25.99 degrees, in an X-ray powder diffraction obtained using Cu K alpha radiation. 16. The method of claim 1, wherein the Form I is characterized by a diffraction pattern substantially similar to that of FIG. 1 . 17. The method of claim 1, wherein the Form I is characterized by a diffraction pattern substantially similar to that of FIG. 2 . 18. A method of treating cystic fibrosis in a mammal comprising administering to the mammal an effective amount of: (a) 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid, characterized as Form I, wherein the Form I is characterized as a monoclinic crystal system in P2 i/n space group with the following unit cell dimensions: a=4.9626 (7) Å α=90° b=12.2994 (18) Å β=93.938 (9)° c=33.075 (4) Å γ=90°.