POLYMORPHIC FORMS OF 3-(4-AMINO-1-OXO-1,3 DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE

• US 20110288127A1
• Filed: 05/26/2011
• Published: 11/24/2011
• Est. Priority Date: 09/04/2003
• Status: Active Grant

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Muller, George W., Cameron, Louise M., Chen, Roger Shen-Chu, Saindane, Manohar T., Jaworsky, Markian S.
• Granted Patent: US 8,431,598 B2
• Time in Patent Office: Days
• US Class Current: 514/323
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: B65D 51/2864 the element being a plug or like element closing a passage between the auxiliary container and the main container
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond

Abstract

Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione are disclosed. Compositions comprising the polymorphic forms, methods of making the polymorphic forms and methods of their use are also disclosed.

Claims

1-28. -28. (canceled)

29. A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline Form A of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having a differential scanning calorimetry thermogram endotherm at approximately 270°

C., wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

30. The solid form of claim 29, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

31. The solid form of claim 29, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

32. The solid form of claim 29, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

42. A pharmaceutical composition comprising a therapeutically effective amount of the solid form of any one of claims 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, and 41, and a pharmaceutically acceptable excipient, diluent, or carrier.

43. The pharmaceutical composition of claim 42, which is a single unit dosage form.

44. The pharmaceutical composition of claim 43, wherein the therapeutically effective amount is about 5 mg, about 10 mg, about 25 mg, or about 50 mg.

33. A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having a differential scanning calorimetry thermogram endotherm at approximately 270°

C. and an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, and 16 degrees 2θ and

a thermogravimetric analysis curve indicative of an unsolvated material, wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

34. The solid form of claim 33, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

35. The solid form of claim 33, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

36. The solid form of claim 33, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

37. The solid form of any one of claims 33, 34, 35, and 36, wherein the X-ray powder diffraction pattern further comprises peaks at approximately 17.5, 20.5, 24 and 26 degrees 2θ

.

38. A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having an X-ray powder diffraction pattern corresponding to the representative X-ray powder diffraction pattern provided in FIG. 1, wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

39. The solid form of claim 38, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

40. The solid form of claim 38, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

41. The solid form of claim 38, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

45. A pharmaceutical composition comprising from about 5 mg to about 25 mg of a solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione having a differential scanning calorimetry thermogram endotherm at approximately 270°

C., and a pharmaceutically acceptable excipient, diluent, or carrier;

wherein the crystalline form is present at greater than about 80% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

46. The pharmaceutical composition of claim 45, wherein the crystalline form is present at greater than about 90% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

47. The pharmaceutical composition of claim 45, wherein the crystalline form is present at greater than about 95% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

48. The pharmaceutical composition of claim 45, wherein the crystalline form is present at greater than about 97% by weight of the total weight of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

49. The pharmaceutical composition of any one of claims 45, 46, 47, and 48, comprising about 5 mg of the solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

50. The pharmaceutical composition of any one of claims 45, 46, 47, and 48, comprising about 10 mg of the solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.

51. The pharmaceutical composition of any one of claims 45, 46, 47, and 48, comprising about 25 mg of the solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione.