IP Library Granted Patent US 9,221,788
Granted Patent B2
US 9,221,788 · App. 13/962,745 · Granted Dec 29, 2015

Salts and solid forms of (S)-3-(4- (4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and compositions comprising and methods of using the same

Inventors: Benjamin M. Cohen (Cranford, NJ); John F. Traverse (Roselle Park, NJ); Jean Xu (Warren, NJ); Ying Li (Springfield, NJ)
Assignee: Celgene Corporation
C07D401/04
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Quick Facts
Patent No.
US 9,221,788
App. No.
13/962,745
Granted
Dec 29, 2015
Kind
B2
Abstract

Salts and solid forms of 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a stereoisomer thereof, are disclosed. Compositions comprising and methods of using the salts and solid forms are also disclosed.

Claims (104)

1. A solid form comprising a salt, hydrate, or solvate of Compound (I-S):

wherein the solid form is crystalline, wherein the solid form

comprises Compound (I-S) and water, having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees 2θ;

comprises Compound (I-S) and THF, having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees 2θ;

comprises a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96 degrees 2θ;

comprises a DMSO solvate of a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 16.88, 18.14, and 20.02 degrees 2θ;

comprises a D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and 25.86 degrees 2θ;

comprises a hemi D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.21, 12.91, and 16.32 degrees 2θ;

comprises a L-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32 degrees 2θ;

comprises a tosylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25 degrees 2θ; or

comprises a (+) camphorsulfonic acid salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.05, 14.61, and 16.82 degrees 2θ.

2. A solid form comprising a racemic Compound (I):

or a salt, hydrate, anhydrate, or solvate thereof, wherein the solid form is crystalline, wherein the solid form

comprises racemic Compound (I), having an XRPD pattern comprising peaks at approximately 4.95, 8.96, and 14.83 degrees 2θ;

comprises racemic Compound (I) and water, having an XRPD pattern comprising peaks at approximately 14.01, 17.28, and 26.21 degrees 2θ;

comprises a HCl salt of racemic Compound (I) and water, having an XRPD pattern comprising peaks at approximately 13.88, 14.30, and 15.36 degrees 2θ; or

comprises a HCl salt of racemic Compound (I) and methanol, having an XRPD pattern comprising peaks at approximately 12.38, 14.54, and 26.10 degrees 2θ.

3. The solid form of claim 1 , comprising Compound (I-S) and water having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees 2θ.

4. The solid form of claim 3 , further comprises peaks at approximately 13.79, 17.15, and 26.00 degrees 2θ.

5. The solid form of claim 3 , comprising Compound (I-S) and water, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 5 .

6. The solid form of claim 1 , comprising Compound (I-S) and THF having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees 2θ.

7. The solid form of claim 6 , further comprises peaks at approximately 6.03 and 18.59 degrees 2θ.

8. The solid form of claim 6 , comprising Compound (I-S) and THF, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 8 .

9. The solid form of claim 1 , comprising a besylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96 degrees 2θ.

10. The solid form of claim 9 , further comprises peaks at approximately 15.48 and 15.92 degrees 2θ.

11. The solid form of claim 9 , comprising a besylate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 11 .

12. The solid form of claim 1 , comprising a DMSO solvate of a besylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 16.88, 18.14, and 20.02 degrees 2θ.

13. The solid form of claim 12 , further comprises peaks at approximately 7.31 and 24.49 degrees 2θ.

14. The solid form of claim 12 , comprising a DMSO solvate of a besylate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 16 .

15. The solid form of claim 1 , comprising a D-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and 25.86 degrees 2θ.

16. The solid form of claim 15 , further comprises peaks at approximately 19.25 and 21.25 degrees 2θ.

17. The solid form of claim 15 , comprising a D-tartrate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 20 .

18. The solid form of claim 1 , comprising a hemi D-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 6.21, 12.91, and 16.32 degrees 2θ.

19. The solid form of claim 18 , further comprises peaks at approximately 12.32 and 19.09 degrees 2θ.

20. The solid form of claim 18 , comprising a hemi D-tartrate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 23 .

21. The solid form of claim 1 , comprising a L-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32 degrees 2θ.

22. The solid form of claim 21 , further comprises peaks at approximately 11.97, 14.41, and 17.08 degrees 2θ.

23. The solid form of claim 21 , comprising a L-tartrate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 26 .

24. The solid form of claim 1 , comprising a tosylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25 degrees 2θ.

25. The solid form of claim 24 , further comprises peaks at approximately 7.41 and 22.97 degrees 2θ.

26. The solid form of claim 24 , comprising a tosylate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 29 .

27. The solid form of claim 1 , comprising a (+) camphorsulfonic acid salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 9.05, 14.61, and 16.82 degrees 2θ.

28. The solid form of claim 27 , further comprises peaks at approximately 13.97, 15.34, and 16.35 degrees 2θ.

29. The solid form of claim 27 , comprising a (+) camphorsulfonic acid salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 32 .

30. A solid form comprising a HCl salt of Compound (I-S):

or a salt, hydrate, anhydrate, or solvate of the HCl salt, wherein the solid form is crystalline, wherein the solid form

is Form A crystal form characterized by an XRPD pattern comprising peaks at approximately 15.09, 15.94, and 22.30 degrees 2θ;

is Form B crystal form characterized by an XRPD pattern comprising peaks at approximately 7.11, 14.20, and 20.71 degrees 2θ;

is Form C crystal form characterized by an XRPD pattern comprising peaks at approximately 6.55, 13.14, and 13.37 degrees 2θ;

is Form D crystal form characterized by an XRPD pattern comprising peaks at approximately 13.52, 14.16, and 25.00 degrees 2θ;

is Form E crystal form characterized by an XRPD pattern comprising peaks at approximately 9.82, 17.06, and 17.73 degrees 2θ;

is Form F crystal form characterized by an XRPD pattern comprising peaks at approximately 13.71, 14.22, and 20.87 degrees 2θ;

is Form G crystal form characterized by an XRPD pattern comprising peaks at approximately 6.85, 20.20, and 20.60 degrees 2θ;

is Form H crystal form characterized by an XRPD pattern comprising peaks at approximately 6.83, 20.19, and 20.58 degrees 2θ;

is Form I crystal form characterized by an XRPD pattern comprising peaks at approximately 13.95, 23.39, and 24.10 degrees 2θ;

is Form J crystal form characterized by an XRPD pattern comprising peaks at approximately 4.86, 13.48, and 20.06 degrees 2θ; or

is Form K crystal form characterized by an XRPD pattern comprising peaks at approximately 7.09, 14.03, and 14.22 degrees 2θ.

31. The solid form of claim 30 , wherein the solid form is Form A crystal form characterized by an XRPD pattern comprising peaks at approximately 15.09, 15.94, and 22.30 degrees 2θ.

32. The solid form of claim 31 , further comprises peaks at approximately 17.65, 22.47, and 26.77 degrees 2θ.

33. The solid form of claim 31 , wherein the solid form is Form A crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 36 .

34. The solid form of claim 31 , which exhibits a thermal event, as characterized by DSC, with a peak temperature of about 261° C. and an onset temperature of about 256° C.

35. The solid form of claim 31 , which exhibits a weight loss of about 0.16% of the total sample weight upon heating from about 25 to about 120° C.

36. The solid form of claim 30 , wherein the solid form is Form B crystal form characterized by an XRPD pattern comprising peaks at approximately 7.11, 14.20, and 20.71 degrees 2θ.

37. The solid form of claim 36 , further comprises peaks at approximately 9.93 and 21.36 degrees 2θ.

38. The solid form of claim 36 , wherein the solid form is Form B crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 44 .

39. The solid form of claim 30 , wherein the solid form is Form C crystal form characterized by an XRPD pattern comprising peaks at approximately 6.55, 13.14, and 13.37 degrees 2θ.

40. The solid form of claim 39 , further comprises peaks at approximately 9.09, 19.62, and 19.80 degrees 2θ.

41. The solid form of claim 39 , wherein the solid form is Form C crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 50 .

42. The solid form of claim 30 , wherein the solid form is Form D crystal form characterized by an XRPD pattern comprising peaks at approximately 13.52, 14.16, and 25.00 degrees 2θ.

43. The solid form of claim 42 , further comprises peaks at approximately 6.82, 8.07, and 15.71 degrees 2θ.

44. The solid form of claim 42 , wherein the solid form is Form D crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 57 .

45. The solid form of claim 30 , wherein the solid form is Form E crystal form characterized by an XRPD pattern comprising peaks at approximately 9.82, 17.06, and 17.73 degrees 2θ.

46. The solid form of claim 45 , further comprises peaks at approximately 16.05, 25.71, and 26.15 degrees 2θ.

47. The solid form of claim 45 , wherein the solid form is Form E crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 64 .

48. The solid form of claim 30 , wherein the solid form is Form F crystal form characterized by an XRPD pattern comprising peaks at approximately 13.71, 14.22, and 20.87 degrees 2θ.

49. The solid form of claim 48 , further comprises peaks at approximately 7.10, 16.35, and 28.36 degrees 2θ.

50. The solid form of claim 48 , wherein the solid form is Form F crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 73 .

51. The solid form of claim 30 , wherein the solid form is Form G crystal form characterized by an XRPD pattern comprising peaks at approximately 6.85, 20.20, and 20.60 degrees 2θ.

52. The solid form of claim 51 , further comprises peaks at approximately 9.56, 13.69, 19.05, and 23.57 degrees 2θ.

53. The solid form of claim 51 , wherein the solid form is Form G crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 82 .

54. The solid form of claim 30 , wherein the solid form is Form H crystal form characterized by an XRPD pattern comprising peaks at approximately 6.83, 20.19, and 20.58 degrees 2θ.

55. The solid form of claim 54 , further comprises peaks at approximately 9.47 and 13.63 degrees 2θ.

56. The solid form of claim 54 , wherein the solid form is Form H crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 86 .

57. The solid form of claim 30 , wherein the solid form is Form I crystal form characterized by an XRPD pattern comprising peaks at approximately 13.95, 23.39, and 24.10 degrees 2θ.

58. The solid form of claim 57 , further comprises peaks at approximately 13.51 and 24.30 degrees 2θ.

59. The solid form of claim 57 , wherein the solid form is Form I crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 90 .

60. The solid form of claim 30 , wherein the solid form is Form J crystal form characterized by an XRPD pattern comprising peaks at approximately 4.86, 13.48, and 20.06 degrees 2θ.

61. The solid form of claim 60 , further comprises peaks at approximately 20.39, 22.15, and 23.45 degrees 2θ.

62. The solid form of claim 60 , wherein the solid form is Form J crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 92 .

63. The solid form of claim 30 , wherein the solid form is Form K crystal form characterized by an XRPD pattern comprising peaks at approximately 7.09, 14.03, and 14.22 degrees 2θ.

64. The solid form of claim 63 , further comprises peaks at approximately 9.35 and 21.60 degrees 2θ.

65. The solid form of claim 63 , wherein the solid form is Form K crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 95 .

66. The solid form of claim 2 , comprising racemic Compound (I) having an XRPD pattern comprising peaks at approximately 4.95, 8.96, and 14.83 degrees 2θ.

67. The solid form of claim 66 , further comprises peaks at approximately 12.67, 14.30, 20.09, and 26.57 degrees 2θ.

68. The solid form of claim 66 , comprising racemic Compound (I), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 97 .

69. The solid form of claim 2 , comprising racemic Compound (I) and water having an XRPD pattern comprising peaks at approximately 14.01, 17.28, and 26.21 degrees 2θ.

70. The solid form of claim 69 , further comprises peaks at approximately 8.34, 11.79, and 17.01 degrees 2θ.

71. The solid form of claim 69 , comprising racemic Compound (I) and water, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 99 .

72. The solid form of claim 2 , comprising a HCl salt of racemic Compound (I) and water having an XRPD pattern comprising peaks at approximately 13.88, 14.30, and 15.36 degrees 2θ.

73. The solid form of claim 72 , further comprises peaks at approximately 9.84, 16.42, and 19.82 degrees 2θ.

74. The solid form of claim 72 , comprising a HCl salt of racemic Compound (I) and water, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 101 .

75. The solid form of claim 2 , comprising a HCl salt of racemic Compound (I) and methanol having an XRPD pattern comprising peaks at approximately 12.38, 14.54, and 26.10 degrees 2θ.

76. The solid form of claim 75 , further comprises peaks at approximately 15.06, 20.00, and 26.86 degrees 2θ.

77. The solid form of claim 75 , comprising a HCl salt of racemic Compound (I) and methanol, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 104 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2014
From: COHEN, BENJAMIN M.; TRAVERSE, JOHN F.; XU, JEAN; LI, YING
To: CELGENE CORPORATION
Reel/Frame 032353/0005 →
Continuity (2)
Provisional Application 61681484 · Aug 9, 2012
Related Publication 20140046057A1 · Feb 13, 2014