Granted Patent
B2
US 12,384,815 · App. 18/411,501 · Granted Aug 12, 2025
2,2-difluoropropionamide derivatives of bardoxolone methyl, polymorphic forms and methods of use thereof
Inventors:
Ahmad Y. Sheikh (Deerfield, IL); Alessandra Mattei (Chicago, IL); Xiu C. Wang (Green Oaks, IL)
Assignee:
REATA PHARMACEUTICALS HOLDINGS, LLC
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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.
Claims (22)
1. A method for ameliorating or effecting any measurable decrease in a seizure disorder in a patient in need thereof, comprising administering to the patient an effective amount of a polymorphic form of a compound having the formula:
wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, or (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ.
2. The method of claim 1 , wherein the seizure disorder is epilepsy.
3. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ.
4. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) substantially as shown in FIG. 53 .
5. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, and having a melting point of about 181.98° C.
6. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, and having a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 54 .
7. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ.
8. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) substantially as shown in FIG. 56 .
9. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ, and having a melting point of about 250.10° C.
10. The method of claim 1 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344 19.444, 19.764, 20.801, and 22.414 °2θ, and having a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 57 .
11. A method of ameliorating or effecting any measurable decrease in a neurodegenerative disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a polymorphic form of a compound having the formula:
wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, or (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ,
wherein the neurodegenerative disease is Parkinson's disease, Alzheimer's disease, multiple sclerosis, Huntington's disease, or amyotrophic lateral sclerosis.
12. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ.
13. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) substantially as shown in FIG. 53 .
14. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, and having a melting point of about 181.98° C.
15. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13.435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, and having a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 54 .
16. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ.
17. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) substantially as shown in FIG. 56 .
18. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ, and having a melting point of about 250.10° C.
19. The method of claim 11 , wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ, and having a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 57 .
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 14, 2025
From: ABBVIE INC.
To: REATA PHARMACEUTICALS HOLDINGS, LLC
Reel/Frame 069866/0393 →
Continuity (6)
Provisional Application
61815502
· Apr 24, 2013
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