Claims for Patent: 8,993,640

Summary for Patent: 8,993,640

Title:	2,2-difluoropropionamide derivatives of bardoxolone methyl, polymorphic forms and methods of use thereof
Abstract:	The present invention relates generally to the compound: N-((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicen-4a-yl)-2,2-difluoropropanamide, polymorphic forms thereof, methods for preparation and use thereof, pharmaceutical compositions thereof, and kits and articles of manufacture thereof.
Inventor(s):	Eric Anderson, Xiaofeng Liu, Andrea Decker
Assignee:	Solvias AG, Reata Pharmaceuticals Holdings LLC
Application Number:	US13/869,833
Patent Claims:	1. A compound of the formula: or a pharmaceutically acceptable salt thereof. 2. A polymorphic form of a compound of the formula: wherein the polymorphic form has an X-ray powder diffraction pattern (CuKα) comprising a halo peak at about 14° 2θ. 3. The polymorphic form of claim 2, wherein the X-ray powder diffraction pattern (CuKα) further comprises a shoulder peak at about 8° 2θ. 4. The polymorphic form of claim 2, wherein the X-ray powder diffraction pattern (CuKα) is as shown in FIG. 59. 5. The polymorphic form of claim 2, further having a Tg from about 150° C. to about 155° C. 6. The polymorphic form of claim 2, further having a differential scanning calorimetry (DSC) curve comprising an endotherm centered from about 150° C. to about 155° C. 7. The polymorphic form of claim 2, having a differential scanning calorimetry (DSC) curve as shown in FIG. 62. 8. A polymorphic form of a compound of the formula: wherein the polymorphic form is a solvate having an X-ray powder diffraction pattern (CuKα) comprising significant peaks at about 5.6, 7.0, 10.6, 12.7, and 14.6° 2θ. 9. The polymorphic form of claim 8, wherein the X-ray powder diffraction pattern (CuKα) is as shown in FIG. 75, top pattern. 10. A polymorphic form of a compound of the formula: wherein the polymorphic form is a solvate having an X-ray powder diffraction pattern (CuKα) comprising significant peaks at about 7.0, 7.8, 8.6, 11.9, 13.9 (double peak), 14.2, and 16.0° 2θ. 11. The polymorphic form of claim 10, wherein the X-ray powder diffraction pattern (CuKα) is as shown in FIG. 75, second pattern from top. 12. A polymorphic form of a compound of the formula: wherein the polymorphic form is an acetonitrile hemisolvate having an X-ray powder diffraction pattern (CuKα) comprising significant peaks at about 7.5, 11.4, 15.6, and 16.6° 2θ. 13. The polymorphic form of claim 12, wherein the X-ray powder diffraction pattern (CuKα) is as shown in FIG. 75, second pattern from bottom. 14. The polymorphic form of claim 12, further having a Tg of about 196° C. 15. The polymorphic form of claim 12, further having a differential scanning calorimetry (DSC) curve comprising an endotherm centered at about 196° C. 16. The polymorphic form of claim 12, having a differential scanning calorimetry (DSC) curve as shown in FIG. 116. 17. A polymorphic form of a compound of the formula: wherein the polymorphic form is a solvate having an X-ray powder diffraction pattern (CuKα) comprising significant peaks at about 6.8, 9.3, 9.5, 10.5, 13.6, and 15.6° 2θ. 18. The polymorphic form of claim 17, wherein the X-ray powder diffraction pattern (CuKα) is as shown in FIG. 75, bottom pattern. 19. A pharmaceutical composition comprising: an active ingredient consisting of a compound of claim 1, and a pharmaceutically acceptable carrier. 20. A method of treating a condition associated with inflammation or oxidative stress, selected from the group consisting of prostate cancer, dermatitis, sepsis, pulmonary inflammation, pulmonary fibrosis, COPD, asthma, mucositis, and ocular inflammation, in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 19. 21. The method of claim 20, wherein the dermatitis is radiation-induced dermatitis. 22. The method of claim 20, wherein the mucositis is mucositis resulting from radiation therapy or chemotherapy. 23. A method of reducing the duration and/or severity of radiation-induced oral mucositis or radiation-induced dermatitis in a patient in need of acute radiation treatment comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 19 prior to and/or after said acute radiation treatment.