IP Library Granted Patent US 8,754,224
Granted Patent B2
US 8,754,224 · App. 13/785,692 · Granted Jun 17, 2014

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

Inventors: Patricia Hurter (Harvard, MA); William Rowe (Medford, MA); Christopher R. Young (Waltham, MA); Adriana Costache (Cambridge, MA); Patrick R. Connelly (Harvard, MA); Mariusz Krawlec (Marlborough, MA); Yuchuan Gong (Waukegan, IL); Yushi Feng (Zionsville, IN); Martin Trudeau (Shannon, CA)
Assignee: Vertex Pharmaceuticals Incorporated
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Quick Facts
Patent No.
US 8,754,224
App. No.
13/785,692
Granted
Jun 17, 2014
Kind
B2
Abstract

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Claims (18)

1. A solid dispersion comprising amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and a polymer, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer (PVP/VA).

2. The solid dispersion of claim 1 , wherein the polymer is polyvinylpyrrolidones (PVP).

3. The solid dispersion of claim 2 , wherein the polymer is present in an amount of from about 10% by weight to about 80% by weight.

4. The solid dispersion of claim 3 , wherein the polymer is present in an amount of less than about 70% by weight.

5. The solid dispersion of claim 1 , wherein the N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide is present in an amount of from about 10% by weight to about 80% by weight.

6. The solid dispersion of claim 1 , further comprising a surfactant.

7. The solid dispersion of claim 6 , wherein the surfactant is sodium lauryl sulfate.

8. The solid dispersion of claim 7 , wherein the surfactant is present in an amount from about 0.1 to about 5%.

9. The solid dispersion of claim 8 , wherein the surfactant is present in 0.5%.

10. The solid dispersion according to claim 1 , wherein the solid dispersion is obtained by spray drying.

11. A pharmaceutical composition comprising amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and a polymer as a solid dispersion, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer (PVP/VA).

12. The pharmaceutical composition of claim 11 , wherein the polymer is polyvinylpyrrolidones (PVP).

13. A solid dispersion comprising N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, a polymer and sodium lauryl sulfate, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer (PVP/VA).

14. The solid dispersion of claim 13 , wherein the polymer is polyvinylpyrrolidones (PVP).

15. A pharmaceutical composition comprising the solid dispersion of claim 13 .

16. Solid amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.

17. Solid amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide comprising less than about 15% crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.

18. A pharmaceutical composition comprising solid amorphous N -[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Oct 14, 2016
From: MACQUARIE US TRADING LLC
To: VERTEX PHARMACEUTICALS INCORPORATED; VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
Reel/Frame 040357/0001 →
ASSIGNEE CHANGE OF ADDRESS Recorded Jan 26, 2016
From: VERTEX PHARMACEUTICALS INCORPORATED
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 037592/0426 →
SECURITY INTEREST Recorded Jul 10, 2014
From: VERTEX PHARMACEUTICALS INCORPORATED; VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
To: MACQUARIE US TRADING LLC
Reel/Frame 033292/0311 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 13, 2013
From: HURTER, PATRICIA; ROWE, WILLIAM; YOUNG, CHRISTOPHER R.; COSTACHE, ADRIANA; CONNELLY, PATRICK R.; KRAWIEC, MARIUSZ; GONG, YUCHUAN; FENG, YUSHI; TRUDEAU, MARTIN
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 029981/0033 →
Continuity (4)
Continuation 13358778 · Jan 26, 2012
Continuation 11647505 · Dec 28, 2006
Provisional Application 60754381 · Dec 28, 2005
Related Publication 20130317060A1 · Nov 28, 2013