Pharmaceutical compositions of therapeutically active compounds

Patent metadata

Field	Value
Publication number	US-10449184-B2
Application number	US-201815949750-A
Country	US
Kind code	B2
Filing date	Apr 10, 2018
Priority date	Mar 14, 2014
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

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. A pharmaceutical composition for oral administration comprising (a) a solid dispersion comprising between 25-75% w/w 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) or a pharmaceutically acceptable salt thereof, and a polymer selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyvinyl acetate phthalate (PVAP), hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose phthalate (HPMCP) and optionally (b) one or more pharmaceutically acceptable carrier(s).

2. The pharmaceutical composition of claim 1 wherein the polymer is HPMCAS.

3. The pharmaceutical composition of claim 2 wherein the solid dispersion is a spray-dried dispersion.

4. The pharmaceutical composition of claim 3 wherein the solid dispersion comprises between about 30 and 70% w/w Compound 1.

5. The pharmaceutical composition of claim 4 wherein the solid dispersion comprises between about 40 and 60% compound 1.

6. The pharmaceutical composition of claim 4 wherein the solid dispersion comprises about 50% w/w Compound 1.

7. The pharmaceutical composition of claim 3 wherein the solid dispersion comprises about 25% Compound 1.

8. The pharmaceutical composition of claim 3 wherein the dispersion is an amorphous dispersion.

9. The pharmaceutical composition of claim 3 wherein the dispersion further comprises a surfactant or inert pharmaceutically acceptable substance.

10. The pharmaceutical composition of claim 9 wherein the surfactant is vitamin E or sodium lauryl sulfate (SLS).

11. The pharmaceutical composition of claim 3 wherein the composition further comprises a filler.

12. The pharmaceutical composition of claim 11 wherein the filler is microcrystalline cellulose.

13. The pharmaceutical composition of claim 3 wherein the composition further comprises a disintegrant.

14. The pharmaceutical composition of claim 13 wherein the disintegrant is croscarmellose sodium.

15. The pharmaceutical composition of claim 3 wherein the composition further comprises a wetting agent.

16. The pharmaceutical composition of claim 15 wherein the wetting agent is sodium lauryl sulfate.

17. The pharmaceutical composition of claim 3 wherein the composition further comprises a glidant.

18. The pharmaceutical composition of claim 17 wherein the glidant is colloidal silicon dioxide.

19. The pharmaceutical composition of claim 3 wherein the composition further comprises a lubricant.

20. The pharmaceutical composition of claim 19 wherein the lubricant is magnesium stearate.

21. The pharmaceutical composition of claim 3 wherein the pharmaceutical composition comprises from between about 25% w/w to about 35% w/w of Compound 1, or a pharmaceutically acceptable salt thereof, from between about 25% w/w to about 35% w/w of hydroxypropylmethylcellulose acetate succinate (HPMCAS), from between about 25% w/w to about 35% w/w of microcrystalline cellulose, from between about 5% w/w to about 7% w/w croscarmellose sodium, from between about 0.5% w/w to about 1.5% w/w sodium lauryl sulfate, about from between about 1% w/w to about 3% w/w colloidal silicon dioxide, and rom between about 0.5% w/w to about 2.5% w/w of magnesium stearate, thereby totaling 100% by weight of the composition.

22. The pharmaceutical composition of claim 3 wherein the pharmaceutical composition comprises, about 30% w/w of compound 1, or a pharmaceutically acceptable salt thereof, about 30% w/w of hydroxypropylmethylcellulose acetate succinate (HPMCAS), about 29.5% w/w of microcrystalline cellulose, about 6% w/w croscarmellose sodium, about 1% w/w sodium lauryl sulfate, about 2% w/w colloidal silicon dioxide, and about 1.5% w/w of magnesium stearate.

23. The pharmaceutical composition of claim 22 wherein the pharmaceutical composition is a tablet.

Assignees

• Agios Pharmaceuticals Inc

Inventors

• Gu Chong-Hui

Classifications

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title