Claims for Patent: 12,281,113

Summary for Patent: 12,281,113

Title:	Crystalline forms of a KRas G12C inhibitor
Abstract:	The present invention relates to crystalline forms of a KRas G12C inhibitor and salt thereof. In particular, the present invention relates to crystalline forms of the KRas G12C inhibitor 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile, pharmaceutical compositions comprising the crystalline forms, processes for preparing the crystalline forms and methods of use thereof.
Inventor(s):	Patricia Andres, Samuel Andrew, Cheng Yi Chen, Susana Del Rio Gancedo, Tawfik Gharbaoui, Jennifer Nelson
Assignee:	Mirati Therapeutics Inc
Application Number:	US18/782,879
Patent Claims:	1. Crystalline Form A of 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile, having an X-ray powder diffraction pattern comprising at least one peak at °2θ selected from 8.6±0.2, 14.6±0.2, 16.9±0.2 and 18.3±0.2. 2. The crystalline form according to claim 1, having an X-ray powder diffraction pattern comprising two or more peaks at °2θ selected from 8.6±0.2, 14.6±0.2, 16.9±0.2 and 18.3±0.2. 3. The crystalline form according to claim 1, having an X-ray powder diffraction pattern comprising peaks at °2θ at 8.6±0.2, 14.6±0.2, 16.9±0.2 and 18.3±0.2. 4. The crystalline form according to claim 2, having an X-ray powder diffraction pattern comprising peaks at °2θ at 5.8±0.2, 8.6±0.2, 12.3±0.2, 13.0±0.2, 14.2±0.2, 14.6±0.2, 16.0±0.2, 16.9±0.2, 18.1±0.2, 18.3±0.2, 20.4±0.2, 21.2±0.2, 23.9±0.2 and 25.5±0.2. 5. The crystalline form according to claim 1, having an XRPD pattern as shown in FIG. 1A or FIG. 1B. 6. The crystalline form according to claim 1, having a DSC thermogram as shown in FIG. 2 . 7. The crystalline form of claim 1, having a thermogravimetric analysis (“TGA”) profile as shown in FIG. 3 . 8. The crystalline form of claim 1, having dynamic vapor sorption (“DVS”) isotherm as shown in FIG. 4 . 9. A pharmaceutical composition comprising the crystalline form of claim 1 and at least one pharmaceutically acceptable excipient and/or diluent. 10. Crystalline Form B of 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile having an X-ray powder diffraction pattern comprising at least one peak at °2θ selected from 16.7±0.2, 17.5±0.2 and 18.8±0.2. 11. The crystalline form according to claim 10, having an X-ray powder diffraction pattern comprising peaks at °2θ at 16.7±0.2, 17.5±0.2 and 18.8±0.2. 12. The crystalline form according to claim 10, having an X-ray powder diffraction pattern comprising two or more peaks at °2θ selected from 5.8±0.2, 13.3±0.2, 13.9±0.2, 14.2±0.2, 15.6±0.2, 15.9±0.2, 16.7±0.2, 17.5±0.2, 17.9±0.2, 18.1±0.2, 18.8±0.2, 19.5±0.2, 19.9±0.2, 21.4±0.2, 21.8±0.2, 23.1±0.2, 23.7±0.2 and 24.7±0.2. 13. The crystalline form according to claim 10, having an X-ray powder diffraction pattern comprising peaks at °2θ at 5.8±0.2, 13.3±0.2, 13.9±0.2, 14.2±0.2, 15.6±0.2, 15.9±0.2, 16.7±0.2, 17.5±0.2, 17.9±0.2, 18.1±0.2, 18.8±0.2, 19.5±0.2, 19.9±0.2, 21.4±0.2, 21.8±0.2, 23.1±0.2, 23.7±0.2 and 24.7±0.2. 14. The crystalline form according to claim 10, having an XRPD pattern as shown in FIG. 5A or FIG. 5B. 15. The crystalline form according to claim 10, having a DSC thermogram as shown in FIG. 6 or FIG. 12 . 16. The crystalline form of claim 10, having a TGA profile as shown in FIG. 7 . 17. The crystalline form of claim 10, having a DVS isotherm as shown in FIG. 8 . 18. A pharmaceutical composition comprising the crystalline form of claim 10 and at least one pharmaceutically acceptable excipient and/or diluent. 19. Crystalline Form C of 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile having an X-ray powder diffraction pattern comprising at least one peak at °2θ selected from 16.4±0.2 and 19.7±0.2. 20. The crystalline form of claim 19, having an X-ray powder diffraction pattern comprising peaks at °2θ at 16.4±0.2 and 19.7±0.2. 21. The crystalline form according to claim 19, having an X-ray powder diffraction pattern comprising two or more peaks at °2θ selected from 5.7±0.2, 13.3±0.2, 13.9±0.2, 14.2±0.2, 15.5±0.2, 16.4±0.2, 17.8±0.2, 18.0±0.2, 19.7±0.2, 23.2±0.2, 23.7±0.2, 24.4±0.2 and 26.7±0.2. 22. The crystalline form according to claim 19, having an X-ray powder diffraction pattern comprising peaks at °2θ at 5.7±0.2, 13.3±0.2, 13.9±0.2, 14.2±0.2, 15.5±0.2, 16.4±0.2, 17.8±0.2, 18.0±0.2, 19.7±0.2, 23.2±0.2, 23.7±0.2, 24.4±0.2 and 26.7±0.2. 23. The crystalline form according to claim 19, having an XRPD pattern as shown in FIG. 9 . 24. The crystalline form according to claim 19, having a DSC thermogram as shown in FIG. 10 . 25. The crystalline form according to claim 19, having a TGA profile as shown in FIG. 10 . 26. The crystalline form according to claim 19, wherein the crystalline form is a hydrate. 27. The crystalline form according to claim 1, wherein the crystalline form comprises less than 1.0% by weight of residual organic solvents. 28. The crystalline form according to claim 10, wherein the crystalline form comprises less than 1.0% by weight of residual organic solvents. 29. The crystalline form according to claim 19, wherein the crystalline form comprises less than 1.0% by weight of residual organic solvents. 30. A pharmaceutical composition comprising the crystalline form of claim 19 and at least one pharmaceutically acceptable excipient and/or diluent.