Solid forms comprising 4-amino-2-(2,6- dioxopiperidine-3-yl)isoindoline-1,3-dione and a coformer, compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10835522-B2
Application number	US-201916459435-A
Country	US
Kind code	B2
Filing date	Jul 1, 2019
Priority date	Mar 26, 2013
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

Provided herein are solid forms comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed.

First claim

What is claimed is:

1. A method of treating relapsed and refractory multiple myeloma, the method comprising administering to a patient dexamethasone in combination with a solid form comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione (pomalidomide); and (b) a coformer; wherein
the coformer is gallic acid and the solid form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 22.98, 26.16, and 26.90 degrees 2θ±0.2 degrees 2θ;
the coformer is vanillin and the solid form has an XRPD pattern comprising peaks at 13.09, 17.30, and 25.61 degrees 2θ±0.2 degrees 2θ;
the coformer is cyclamic acid and the solid form has an XRPD pattern comprising peaks at 6.42, 7.88, and 15.73 degrees 2θ±0.2 degrees 2θ;
the coformer is D-glucose and the solid form has an XRPD pattern comprising peaks at 17.09, 20.68, and 25.52 degrees 2θ±0.2 degrees 2θ;
the coformer is propyl gallate and the solid form has an XRPD pattern comprising peaks at 7.78, 25.23, and 25.61 degrees 2θ±0.2 degrees 2θ;
the coformer is saccharin and the solid form has an XRPD pattern comprising peaks at 15.98, 19.09, and 25.10 degrees 2θ±0.2 degrees 2θ;
the coformer is sodium lauryl sulfate and the solid form has an XRPD pattern comprising peaks at 2.66, 5.30, and 7.93 degrees 2θ±0.2 degrees 2θ;
the coformer is magnesium bromide and the solid form has an XRPD pattern comprising peaks at 3.23, 28.76, and 29.95 degrees 2θ±0.2 degrees 2θ;
the coformer is malonic acid and the solid form has an XRPD pattern comprising peaks at 12.23, 16.63, and 25.58 degrees 2θ±0.2 degrees 2θ;
the coformer is maltol and the solid form has an XRPD pattern comprising peaks at 16.51, 17.09, and 25.73 degrees 2θ±0.2 degrees 2θ;
the coformer is methyl paraben and the solid form has an XRPD pattern comprising peaks at 18.73, 25.69, and 26.70 degrees 2θ±0.2 degrees 2θ; or
the coformer is zinc chloride and the solid form has an XRPD pattern comprising peaks at 2.38, 17.17, and 25.71 degrees 2θ±0.2 degrees 2θ.

2. The method of claim 1 , wherein the coformer is gallic acid and the solid form has an X-ray powder diffraction pattern comprising peaks at 22.98, 26.16, and 26.90 degrees 2θ±0.2 degrees 2θ.

3. The method of claim 2 , having an X-ray powder diffraction pattern further comprising peaks at 15.52, 18.42 and 23.20 degrees 2θ±0.2 degrees 2θ.

4. The method of claim 2 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 1 .

5. The method of claim 1 , wherein the coformer is vanillin and the solid form has an X-ray powder diffraction pattern comprising peaks at 13.09, 17.30, and 25.61 degrees 2θ±0.2 degrees 2θ.

6. The method of claim 5 , having an X-ray powder diffraction pattern further comprising peaks at 12.25, 16.91, and 28.01 degrees 2θ±0.2 degrees 2θ.

7. The method of claim 5 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 2 .

8. The method of claim 1 , wherein the coformer is cyclamic acid and the solid form has an X-ray powder diffraction pattern comprising peaks at 6.42, 7.88, and 15.73 degrees 2θ±0.2 degrees 2θ.

9. The method of claim 8 , having an X-ray powder diffraction pattern further comprising peaks at 18.54 and 19.25 degrees 2θ±0.2 degrees 2θ.

10. The method of claim 8 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 3 .

11. The method of claim 1 , wherein the coformer is D-glucose and the solid form has an X-ray powder diffraction pattern comprising peaks at 17.09, 20.68, and 25.52 degrees 2θ±0.2 degrees 2θ.

12. The method of claim 11 , having an X-ray powder diffraction pattern further comprising peaks at 12.31, 14.08, and 17.35 degrees 2θ±0.2 degrees 2θ.

13. The method of claim 11 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 4 .

14. The method of claim 1 , wherein the coformer is propyl gallate and the solid form has an X-ray powder diffraction pattern comprising peaks at 7.78, 25.23, and 25.61 degrees 2θ±0.2 degrees 2θ.

15. The method of claim 14 , having an X-ray powder diffraction pattern further comprising peaks at 17.35 and 24.29 degrees 2θ±0.2 degrees 2θ.

16. The method of claim 14 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 5 .

17. The method of claim 1 , wherein the coformer is saccharin and the solid form has an X-ray powder diffraction pattern comprising peaks at 15.98, 19.09, and 25.10 degrees 2θ±0.2 degrees 2θ.

18. The method of claim 17 , having an X-ray powder diffraction pattern further comprising peaks at 20.07 and 25.73 degrees 2θ±0.2 degrees 2θ.

19. The method of claim 17 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 6 .

20. The method of claim 1 , wherein the coformer is sodium lauryl sulfate and the solid form has an X-ray powder diffraction pattern comprising peaks at 2.66, 5.30, and 7.93 degrees 2θ±0.2 degrees 2θ.

21. The method of claim 20 , having an X-ray powder diffraction pattern further comprising a peak at 2.20 degrees 2θ±0.2 degrees 2θ.

22. The method of claim 20 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 7 .

23. The method of claim 1 , wherein the coformer is magnesium bromide and the solid form has an X-ray powder diffraction pattern comprising peaks at 3.23, 28.76, and 29.95 degrees 2θ±0.2 degrees 2θ.

24. The method of claim 23 , having an X-ray powder diffraction pattern further comprising peaks at 25.72 and 29.87 degrees 2θ±0.2 degrees 2θ.

25. The method of claim 23 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 8 .

26. The method of claim 1 , wherein the coformer is malonic acid and the solid form has an X-ray powder diffraction pattern comprising peaks at 12.23, 16.63, and 25.58 degrees 2θ±0.2 degrees 2θ.

27. The method of claim 26 , having an X-ray powder diffraction pattern further comprising peaks at 17.27 and 24.29 degrees 2θ±0.2 degrees 2θ.

28. The method of claim 26 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 9 .

29. The method of claim 1 , wherein the coformer is maltol and the solid form has an X-ray powder diffraction pattern comprising peaks at 16.51, 17.09, and 25.73 degrees 2θ±0.2 degrees 2θ.

30. The method of claim 29 , having an X-ray powder diffraction pattern further comprising peaks at 13.93 and 24.25 degrees 2θ±0.2 degrees 2θ.

31. The method of claim 29 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 10 .

32. The method of claim 1 , wherein the coformer is methyl paraben and the solid form has an X-ray powder diffraction pattern comprising peaks at 18.73, 25.69, and 26.70 degrees 2θ±0.2 degrees 2θ.

33. The method of claim 32 , having an X-ray powder diffraction pattern further comprising peaks at 13.90 and 21.98 degrees 2θ±0.2 degrees 2θ.

34. The method of claim 32 , having an X-ray powder diffraction pattern substantially similar to the XRPD pattern presented in FIG. 11 .

35. The method of claim 1 , wherei

Assignees

• Celgene Corp

Inventors

• Stahly G Patrick
• Jonaitis David
• Hui Ho-Wah
• Klopfer Kevin J

Classifications

• C07D309/40

  Oxygen atoms attached in positions 3 and 4, e.g. maltol · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K31/454 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• C07D275/06

  with hetero atoms directly attached to the ring sulfur atom · CPC title

• C07C65/03

  monocyclic and having all hydroxy or O-metal groups bound to the ring · CPC title