Pharmaceutical compositions of therapeutically active compounds

Patent metadata

Field	Value
Publication number	US-9968595-B2
Application number	US-201515125880-A
Country	US
Kind code	B2
Filing date	Mar 13, 2015
Priority date	Mar 14, 2014
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

Provided are compounds and pharmaceutical compositions useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound or pharmaceutical composition described herein.

First claim

I claim:

1. Crystalline Form 1 of (S)-N-((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (Compound 1)characterized by one or more X-ray powder diffraction (XRPD) peaks at 2θ angles (±0.2°) selected from 8.6°, 13.2°, 15.6°, 18.5°, 19.6°, 20.6°, 21.6°, 26.4° and 27.3°.

2. The crystalline Form 1 of claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles (±0.2°) 8.6°, 15.6°, 18.5°, and 21.6°.

3. The crystalline Form 1 of claim 2 wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 2θ angles (±0.2°) 20.6° and 26.4°.

4. Crystalline Form 2 of (S)-N-((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (Compound 1) characterized by one or more X-ray powder diffraction (XRPD) peaks at 2θ angles (±0.2°) selected from 9.8°, 11.6°, 14.9°, 16.5°, 19.6°, 20.1°, 22.5°, 23.0°, 25.0° and 31.4°.

5. The crystalline Form 2 of claim 4 characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles (±0.2°) 9.8°, 11.6°, 19.6°, and 23.0°.

6. The crystalline Form 2 of claim 5 wherein the XRPD pattern further comprises peaks at 2θ angles (±0.2°) 22.5° and 31.4°.

7. A process for preparing a solid dispersion of Compound 1 comprising: forming a mixture of crystalline Form 1 of Compound 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles (±0.2°) 8.6°, 15.6°, 18.5°, and 21.6°, one or more polymers, and one or more solvents; and rapidly removing the one or more solvents so as to form a solid dispersion comprising Compound 1.

8. The process of claim 7 wherein the one or more solvents are removed by spray drying.

9. The process of claim 7 wherein the one or more solvents are removed by fluidized spray drying.

10. The process of claim 7 wherein the solid dispersion comprises 20% -80% w/w of Compound 1.

11. The process of claim 7 wherein the solid dispersion comprises about 50% w/w Compound 1.

12. A process for preparing a solid dispersion of Compound 1 comprising forming a mixture of crystalline Form 2 of Compound 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles (±0.2°) 9.8°, 11.6°, 19.6°, and 23.0°, one or more polymers, and one or more solvents; and rapidly removing the one or more solvents so as to form a solid dispersion comprising Compound 1.

13. The process of claim 12 wherein the one or more solvents are removed by spray drying.

14. The process of claim 12 wherein the one or more solvents are removed by fluidized spray drying.

15. The process of claim 12 wherein the solid dispersion comprises 20%-80% w/w of Compound 1.

16. The process of claim 12 wherein the solid dispersion comprises about 50% w/w Compound 1.

17. A pharmaceutical composition comprising a solid dispersion comprising Compound 1 and one or more polymers, and optionally at least one pharmaceutically acceptable excipient, wherein the solid dispersion is made according to the process of claim 7 or claim 12 .

18. The pharmaceutical composition of claim 17 wherein the solid dispersion comprises about 20%-80% w/w of Compound 1.

19. The pharmaceutical composition of claim 17 wherein the solid dispersion comprises about 50% w/w of Compound 1 and 50% w/w of polymer(s).

20. The pharmaceutical composition of claim 17 , wherein the solid dispersion comprises one or more polymers chosen from HPMCAS (hydroxypropylmethylcelulose acetate succinate), PVAP (polyvinyl acetate phthalate), HPMC (hydroxypropylmethylcellulose), and HPMCP (hydroxypropylmethylcellulose phthalate).

21. The pharmaceutical composition of claim 20 wherein the solid dispersion is substantially amorphous.

22. A method of treating acute myelogenous/myeloid leukemia (AML) characterized by the presence of a mutant allele of IDH1, the method comprising administering to a human subject in need thereof a pharmaceutical composition according to claim 17 .

Assignees

• Agios Pharmaceuticals Inc

Inventors

• Gu Chong-Hui

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61K9/146

  with organic macromolecular compounds · CPC title