Claims for Patent: 11,091,459

Summary for Patent: 11,091,459

Title:	Niraparib compositions
Abstract:	The present invention relates to compositions comprising the compound niraparib, in particular certain solid forms of niraparib.
Inventor(s):	Wu; George (Waltham, MA), Chaber; John (Waltham, MA), McKeown; Arlene E. (Rahway, NJ), Foley; Jennifer R. (Rahway, NJ)
Assignee:	Tesaro, Inc. (Waltham, MA) Merck Sharp & Dohme Corp. (Rahway, NJ)
Application Number:	16/584,401
Patent Claims:	1. A composition comprising crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate substantially free of Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate and Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.5.+-.0.2, 24.9.+-.0.2, and 26.0.+-.0.2 degrees, and is further characterized by at least two diffraction angles selected from a group consisting of 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees, and wherein substantially free of Form II and Form III means the composition comprises less than about 6% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II, and Form III; and wherein Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.7.+-.0.3, 12.8.+-.0.3, 17.9.+-.0.3, 19.7.+-.0.3, and 21.8.+-.0.3 degrees; and Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate is substantially characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 17.8.+-.0.2, 19.0.+-.0.2, and 22.8.+-.0.2 degrees. 2. The composition of claim 1, wherein the crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction pattern substantially in accordance with FIG. 1. 3. The composition of claim 1, wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees. 4. The composition of claim 1, wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) comprising at least three diffraction angles selected from a group consisting of 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees. 5. The composition of claim 1, wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) comprising at least four diffraction angles selected from a group consisting of 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees. 6. The composition of claim 1, wherein the crystalline Form I is characterized by a scanning differential calorimetry pattern substantially as shown in FIG. 2. 7. The composition of claim 1, wherein the crystalline Form I is characterized by a Raman spectroscopy pattern substantially as shown in FIG. 3. 8. The composition of claim 1, wherein the crystalline Form I is characterized by a dynamic water vapor sorption pattern substantially as shown in FIG. 5. 9. The composition of claim 1, wherein the crystalline Form I is characterized by an infrared spectroscopy pattern substantially as shown in FIG. 4. 10. The composition of claim 1, wherein the presence of Form III is characterized by at least one diffraction angle selected from a group consisting of 2.theta. values of 17.8.+-.0.2, 19.0.+-.0.2, and 22.8.+-.0.2 degrees. 11. The composition of claim 1, wherein substantially free of Form II and Form III means less than about 4% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II and Form III. 12. The composition of claim 1, wherein substantially free of Form II and Form III means less than about 3% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II and Form III. 13. The composition of claim 1, wherein substantially free of Form II and Form III means less than about 2% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II and Form III. 14. The composition of claim 1, wherein substantially free of Form II and Form III means less than about 1% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II and Form III. 15. A method of making crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate substantially free of Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate and Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, comprising dissolving a composition comprising Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate or Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, or a mixture thereof, in a solvent having a water:organic solvent ratio of about 10:1 to about 400:1 (v/v), and crystallizing the crystalline Form I, wherein crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.5.+-.0.2, 24.9.+-.0.2, and 26.0.+-.0.2 degrees, and is further characterized by at least two diffraction angles selected from a group consisting of 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees; Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.7.+-.0.3, 12.8.+-.0.3, 17.9.+-.0.3, 19.7.+-.0.3, and 21.8.+-.0.3 degrees; and Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate is substantially characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 17.8.+-.0.2, 19.0.+-.0.2, and 22.8.+-.0.2 degrees. 16. The composition of claim 1, prepared by dissolving a composition comprising Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate or Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, or a mixture thereof, in a solvent having a water:organic solvent ratio of about 10:1 to about 400:1 (v/v), and crystallizing the crystalline Form I. 17. The composition of claim 16, wherein the water:organic solvent ratio is about 10:1 (v/v), about 50:1 (v/v), about 100:1 (v/v), about 200:1 (v/v), about 300:1 (v/v), or about 400:1 (v/v). 18. The composition of claim 16, wherein the organic solvent is acetone, methyl ethyl ketone, acetonitrile, methyl tert-butyl ether, dioxane, dimethyl sulfoxide, or any combination thereof. 19. The composition of claim 16, wherein the organic solvent is 2-propanol, acetic acid, formic acid, or any combination thereof. 20. The composition of claim 1, wherein the composition is a pharmaceutical composition. 21. A pharmaceutical composition comprising the composition of claim 1, and at least one pharmaceutically acceptable excipient. 22. The pharmaceutical composition of claim 21, wherein the composition is in an oral dosage form. 23. The pharmaceutical composition of claim 22, wherein the oral dosage form is a tablet or capsule. 24. An article of manufacture comprising multiple unit doses of the pharmaceutical composition of claim 23 in a sealed container with written instructions for use. 25. The article of manufacture of claim 24, further comprising an induction seal, desiccant, or any combination thereof. 26. The pharmaceutical composition of claim 21 wherein the composition is in unit dose form. 27. A composition comprising crystalline Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate substantially free of crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate, wherein the crystalline Form II is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.7.+-.0.3, 12.8.+-.0.3, 17.9.+-.0.3, 19.7.+-.0.3, and 21.8.+-.0.3 degrees; and wherein crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.5.+-.0.2, 24.9.+-.0.2, and 26.0.+-.0.2 degrees, and is further characterized by at least two diffraction angles selected from a group consisting of 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees. 28. The composition of claim 27, wherein the crystalline Form II is substantially characterized by an X-ray powder diffraction pattern substantially in accordance with FIG. 9 for Form II. 29. A composition comprising crystalline Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate substantially free of crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate, wherein the crystalline Form III is substantially characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 17.8.+-.0.2, 19.0.+-.0.2, and 22.8.+-.0.2 degrees; and wherein crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2.theta. values of 9.5.+-.0.2, 24.9.+-.0.2, and 26.0.+-.0.2 degrees, and is further characterized by at least two diffraction angles selected from a group consisting of 2.theta. values of 12.4.+-.0.2, 13.2.+-.0.2, 17.4.+-.0.2, 18.4.+-.0.2, 21.0.+-.0.2, 25.6.+-.0.2, and 26.9.+-.0.2 degrees. 30. The composition of claim 29, wherein the crystalline Form III is substantially characterized by an X-ray powder diffraction pattern substantially in accordance with FIG. 9 for Form III.