Claims for Patent: 12,410,189

Summary for Patent: 12,410,189

Title:	Polymorphs and solid forms of (S)-2-2((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:	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:
Inventor(s):	Paroma Chakravarty, Chong Han, Sean M. Kelly, Karthik Nagapudi, Scott Savage
Assignee:	Genentech Inc
Application Number:	US18/101,951
Patent Claims:	1. A method for the treatment of breast cancer in a subject in need thereof comprising administering to the subject an effective amount of 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 designated the Form A polymorph that exhibits an X-ray powder diffraction pattern having a characteristic peak expressed in degrees 2-theta at approximately 5.7, 11.4, and 19.0. 2. A method for the treatment of breast cancer in a subject in need thereof comprising administering to the subject an effective amount of 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 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. 3. A method for the treatment of breast cancer in a subject in need thereof comprising administering to the subject an effective amount of 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 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. 4. The method of claim 1, wherein the cancer is a hormone receptor positive (HR+) breast cancer. 5. The method of claim 1, wherein the cancer is a HR-positive and HER2-negative breast cancer expressing a PIK3CA mutation. 6. The method of claim 1, wherein the cancer expresses a PIK3CA mutant selected from the group consisting of E542K, E545K, Q546R, H1047L and H1047R. 7. The method of claim 1, wherein the method further comprises one or more additional therapeutic agents. 8. The method of claim 7, wherein the one or more additional therapeutic agents are selected from the group consisting of 5-FU, docetaxel, eribulin, gemcitabine, cobimetinib, ipatasertib, paclitaxel, tamoxifen, fulvestrant, GDC-0810, dexamethasone, palbociclib, bevacizumab, pertuzumab, trastuzumab emtansine, trastuzumab and letrozole. 9. The method of claim 7, wherein the one or more additional therapeutic agents are selected from the group consisting of a CDK4/6 inhibitor, a selective estrogen receptor degrader, and an aromatase inhibitor. 10. The method of claim 7, wherein the one or more additional therapeutic agents are selected from the group consisting of palbociclib, fulvestrant, and letrozole. 11. The method of claim 1, wherein the Form A polymorph 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. 12. The method of claim 1, wherein the Form A polymorph is characterized by the X-ray powder diffraction pattern substantially as shown in FIG. 4 . 13. The method of claim 1, wherein the Form A polymorph is 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. 14. The method of claim 1, wherein the Form A polymorph is 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. 15. The method of claim 2, wherein the cancer is a hormone receptor positive (HR+) breast cancer. 16. The method of claim 2, wherein the cancer expresses a PIK3CA mutant selected from the group consisting of E542K, E545K, Q546R, H1047L and H1047R. 17. The method of claim 3, wherein the cancer is a hormone receptor positive (HR+) breast cancer. 18. The method of claim 3, wherein the cancer expresses a PIK3CA mutant selected from the group consisting of E542K, E545K, Q546R, H1047L and H1047R.