IP Library Granted Patent US 8,471,029
Granted Patent B2
US 8,471,029 · App. 13/053,172 · Granted Jun 25, 2013

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

Inventors: Sneha G. Arekar (Malden, MA); Steven C. Johnston (Bolton, MA); Mariusz Krawiec (Marlborough, MA); Ales Medek (Winchester, MA); Praveen Mudunuri (Waltham, MA); Mark Jeffrey Sullivan (Framingham, MA)
Assignee: Vertex Pharmaceutical Incorporated
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Quick Facts
Patent No.
US 8,471,029
App. No.
13/053,172
Granted
Jun 25, 2013
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 (21)

1. Crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) characterized as Form C, wherein Form C is characterized by a peak at about 152.0 ppm in a 13 C SSNMR spectrum, and wherein the Form C is isolated and purified.

2. Form C according to claim 1 , characterized by a peak at about 135.4 ppm in a 13 C SSNMR spectrum.

3. Form C according to claim 2 , characterized by a peak at about 131.8 ppm in a 13 C SSNMR spectrum.

4. Form C according to claim 3 , characterized by a peak at about 117.0 ppm in a 13 C SSNMR spectrum.

5. Form C according to claim 4 , characterized by a peak at about 130.2 ppm in a 13 C SSNMR spectrum.

6. Form C according to claim 5 , characterized by a peak at about 124.8 ppm in a 13 C SSNMR spectrum.

7. Form C according to claim 6 , characterized by a peak at about 34.5 ppm in a 13 C SSNMR spectrum.

8. Form C according to claim 1 , characterized by one or more peaks in a 13 C SSNMR spectrum selected from about 152.0 ppm, about 135.4 ppm, about 131.8 ppm, about 130.2, about 124.8 ppm, about 117.0 ppm and about 34.5 ppm.

9. Form C according to claim 1 , characterized by a peak at about 152.0 ppm, a peak at about 135.4 ppm, a peak at about 131.8 ppm and a peak at about 117.0 ppm in a 13 C SSNMR spectrum.

10. Form C according to claim 9 , further characterized by a peak at about 130.2 ppm, a peak at about 124.8 ppm and a peak at about 34.5 ppm in a 13 C SSNMR spectrum.

11. Form C according to claim 1 , wherein Form C is characterized by a single crystal which is determined to possess a monoclinic crystal system, a P2 1 /c space group, and the following unit cell dimensions:

a=12.211 Angstroms;

b=5.961 Angstroms;

c=32.662 Angstroms;

α=90.00°;

β=119.62°; and

γ=90.00°.

12. Form C according to claim 1 , wherein Form C is characterized by a peak at about 6.2, a peak at about 7.5, a peak at about 8.3, a peak at about 12.4, a peak at about 14.6, a peak at about 17.9, a peak at about 20.5 and a peak at about 20.9 degrees as measured on a 2-Theta scale in an XRPD diffraction pattern.

13. A pharmaceutical composition comprising Form C according to claim 1 , 11 , or 12 , and a pharmaceutically acceptable adjuvant or carrier.

14. A pharmaceutical composition according to claim 13 , further comprising an additional agent selected from a mucolytic agent, bronchodilator, an antibiotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator other than Form C, or a nutritional agent.

15. A pharmaceutical composition according to claim 14 , wherein the additional agent is a CFTR modulator other than Form C.

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 Feb 17, 2016
From: VERTEX PHARMACEUTICALS INCORPORATED
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 037845/0106 →
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 Apr 26, 2011
From: AREKAR, SNEHA G.; JOHNSTON, STEVEN C.; KRAWIEC, MARIUSZ; MEDEK, ALES; MUDUNURI, PRAVEEN; SULLIVAN, MARK JEFFREY
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 026180/0209 →
Continuity (2)
Provisional Application 61315885 · Mar 19, 2010
Related Publication 20110230519A1 · Sep 22, 2011