Claims for Patent: 11,028,100

Summary for Patent: 11,028,100

Title:	Polymorphs and solid forms of (s)-2-((2-((s)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide, and methods of production
Abstract:	The present invention relates to crystalline polymorph forms of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide (GDC-0077), having the structure, Formula I:or stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, and processes of preparing the polymorph forms.
Inventor(s):	Paroma Chakravarty, Chong Han, Sean M. Kelly, Karthik Nagapudi, Scott Savage
Assignee:	Genentech Inc
Application Number:	US16/875,537
Patent Claims:	1. A crystalline, anhydrate polymorph of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide having the structure: said polymorph is designated the Form A polymorph that exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at approximately 5.7, 11.4, 17.2, 19.0, 19.7, and 24.4. 2. A crystalline, anhydrate polymorph of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide having the structure: said polymorph is designated the Form A polymorph characterized by e X-ray powder diffraction pattern substantially as shown in FIG. 4. 3. A crystalline, anhydrate polymorph of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide having the structure: said polymorph is designated the Form A polymorph characterized by the X-ray powder diffraction peaks shown in Table 2, and a differential scanning calorimetry DSC shows a melting endotherm at approximately 212 to 215° C. 4. A crystalline, anhydrate polymorph of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide having the structure: said polymorph is designated the Form A polymorph characterized by the 13C SSNMR (solid-state nuclear magnetic resonance) spectra substantially as shown in FIG. 7A, and the 19F SSNMR (solid-state nuclear magnetic resonance) spectra substantially as shown in FIG. 7B. 5. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline, anhydrate polymorph of claim 1, and a pharmaceutically acceptable carrier, glidant, diluent, or excipient. 6. The pharmaceutical composition of claim 5 wherein the therapeutically effective amount is from about 1 to about 100 mg. 7. The pharmaceutical composition of claim 5 wherein the therapeutically, effective amount is from about 3 to about 15 mg. 8. The pharmaceutical composition of claim 5 wherein the therapeutically effective amount is about 9 mg. 9. The pharmaceutical composition of claim 5 wherein the crystalline, anhydrate polymorph is milled. 10. The pharmaceutical composition of claim 5 in the form of a tablet. 11. The pharmaceutical composition of claim 10 wherein the therapeutically, effective amount is from about 3 to about 15 mg. 12. The pharmaceutical composition of claim 10 wherein the therapeutically effective amount is about 9 mg. 13. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline, anhydrate polymorph of claim 2, and a pharmaceutically acceptable carrier, glidant, diluent, or excipient. 14. The pharmaceutical composition of claim 13 in the form of a tablet. 15. The pharmaceutical composition of claim 14 wherein the therapeutically effective amount is from about 3 to about 15 mg. 16. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline, anhydrate polymorph of claim 3, and a pharmaceutically acceptable carrier, glidant, diluent, or excipient. 17. The pharmaceutical composition of claim 16 in the form of a tablet. 18. The pharmaceutical composition of claim 17 wherein the therapeutically effective amount is from about 3 to about 15 mg. 19. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline, anhydrate polymorph of claim 4, and a pharmaceutically acceptable carrier, glidant, diluent, or excipient. 20. The pharmaceutical composition of claim 19 in the form of a tablet. 21. The pharmaceutical composition of claim 20 wherein the therapeutically effective amount is from about 3 to about 15 mg. 22. A crystalline, anhydrate polymorph of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide having the structure: said polymorph is designated the Form D polymorph that exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at approximately 7.5, 8.6, 10.8, 16.8, 19.2, and 20.4. 23. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline, anhydrate polymorph of claim 22, and a pharmaceutically acceptable carrier, glidant, diluent, or excipient. 24. A crystalline, trihydrate polymorph of (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide having the structure: said polymorph is designated the Form B polymorph that exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at approximately 5.4, 10.5, and 25.2. 25. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline, trihydrate polymorph of claim 24, and a pharmaceutically acceptable carrier, glidant, diluent, or excipient.