Crystalline forms of a Bruton's tyrosine kinase inhibitor

Patent metadata

Field	Value
Publication number	US-10106548-B2
Application number	US-201815900660-A
Country	US
Kind code	B2
Filing date	Feb 20, 2018
Priority date	Jun 4, 2012
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

First claim

What is claimed is:

1. A crystalline form of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has a differential scanning calorimetry (DSC) thermogram having an endotherm with a peak at about 157° C.

2. The crystalline form of claim 1 , wherein the endotherm has an onset at about 154° C.

3. The crystalline form of claim 1 , wherein the DSC thermogram further comprises an exotherm at about 159° C.

4. The crystalline form of claim 1 , wherein the crystalline form is unsolvated.

5. The crystalline form of claim 2 , wherein the crystalline form is unsolvated.

6. The crystalline form of claim 3 , wherein the crystalline form is unsolvated.

7. The crystalline form of claim 1 , wherein the crystalline form has a thermo-gravitrimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4 .

8. The crystalline form of claim 2 , wherein the crystalline form has a thermo-gravitrimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4 .

9. The crystalline form of claim 3 , wherein the crystalline form has a thermo-gravitrimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4 .

10. The crystalline form of claim 4 , wherein the crystalline form has a thermo-gravitrimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4 .

11. The crystalline form of claim 5 , wherein the crystalline form has a thermo-gravitrimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4 .

12. The crystalline form of claim 6 , wherein the crystalline form has a thermo-gravitrimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4 .

13. The crystalline form of claim 1 , wherein the DSC thermogram was generated by heating the crystalline form at a rate of 10° C./min.

14. The crystalline form of claim 4 , wherein the DSC thermogram was generated by heating the crystalline form at a rate of 10° C./min.

15. A crystalline form of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has an X-ray powder diffraction (XRPD) pattern comprising a 2-Theta peak at about 18.9°.

16. The crystalline form of claim 15 , wherein the XRPD pattern further comprises a 2-Theta peak at about 16.1°.

17. The crystalline form of claim 15 , wherein the XRPD pattern further comprises a 2-Theta peak at about 21.6°.

18. The crystalline form of claim 15 , wherein the crystalline form is unsolvated.

19. The crystalline form of claim 16 , wherein the crystalline form is unsolvated.

20. The crystalline form of claim 17 , wherein the crystalline form is unsolvated.

21. A crystalline form of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has an XRPD pattern comprising a 2-Theta peak at about 5.7°.

22. The crystalline form of claim 21 , wherein the XRPD pattern further comprises a 2-Theta peak at about 16.1°.

23. The crystalline form of claim 21 , wherein the XRPD pattern further comprises a 2-Theta peak at about 18.9°.

24. The crystalline form of claim 21 , wherein the XRPD pattern further comprises a 2-Theta peak at about 21.6°.

25. The crystalline form of claim 21 , wherein the crystalline form is unsolvated.

26. A crystalline form of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has an XRPD pattern comprising a 2-Theta peak at about 21.3°.

27. A pharmaceutical formulation comprising the crystalline form of claim 1 and at least one pharmaceutically acceptable ingredient.

28. The pharmaceutical formulation of claim 27 , wherein the crystalline form is unsolvated.

29. The pharmaceutical formulation of claim 28 , wherein the crystalline form has a TGA thermogram substantially similar to the one set forth in FIG. 4 .

30. The pharmaceutical formulation of claim 27 , wherein the DSC thermogram was generated by heating the crystalline form at a rate of 10° C./min.

Assignees

• Pharmacyclics Llc

Inventors

• Purro Norbert
• Smyth Mark S
• Goldman Erick
• Wirth David D

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/06

  Antianaemics · CPC title