IP Library Granted Patent US 9,242,917
Granted Patent B2
US 9,242,917 · App. 14/239,389 · Granted Jan 26, 2016

Crystal forms of a HCV protease inhibitor

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Quick Facts
Patent No.
US 9,242,917
App. No.
14/239,389
Granted
Jan 26, 2016
Kind
B2
Abstract

The present invention relates to different forms of a HCV inhibitory compound.

Claims (13)

1. Compound A having a form selected from the group consisting of:

a) Hydrate III, wherein Hydrate III is characterized by (i) an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 20.5, 5.0, and 18.2; and/or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 5.14, 6.31, 12.49, 18.35, 26.81, 28.03, 30.33, 31.27, 34.95, 35.99, 38.68, 42.01, 54.93, 56.39, 60.14, 74.20, 107.02, 120.11, 121.60, 129.73, 134.35, 135.95, 142.89, 148.47, 155.37, 157.32, 160.90, 168.32, 172.17, and 175.53 ppm;

b) Hydrate II, wherein Hydrate II is characterized by an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 11.7, 16.6, and 11.2;

c) a crystalline Na salt characterized by an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 18.4, 9.1, and 9.8;

d) Hydrate I, wherein Hydrate I is characterized by (i) an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 8.6, 20.6, and 26.6; and/or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 4.22, 7.23, 11.45, 17.79, 24.04, 26.95, 28.29, 31.15, 32.47, 32.47, 33.46, 34.03, 35.74, 42.32, 53.50, 56.05, 56.96, 77.49, 108.95, 119.65, 122.55, 131.05, 133.13, 135.38, 142.28, 150.78, 156.03, 157.99, 161.36, 171.40, 173.42, 174.30 ppm;

e) Hydrate IV, wherein Hydrate IV is characterized by (i) an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 14.7, 11.5, and 7.1; and/or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 3.90, 5.30, 6.99, 10.49, 13.13, 17.81, 24.73, 27.52, 28.14, 29.42, 31.02, 32.80, 36.08, 39.22, 42.45, 53.62, 55.93, 59.14, 60.76, 74.77, 109.22, 111.19, 11.38, 120.24, 122.50, 133.96, 139.74, 147.2, 148.90, 154.65, 158.25, 159.53, 160.12, 170.14, 171.05, 172.08, 173.47, and 174.46 ppm;

f) Hydrate V, wherein Hydrate V is characterized by (i) an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 9.1, 18.3, and 19.8; and/or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 7.86, 8.92, 13.10, 18.31, 23.72, 27.44, 28.47, 30.77, 35.79, 36.25, 37.15, 37.15, 42.95, 53.13, 55.67, 57.31, 60.47, 62.06, 75.09, 110.59, 112.24, 118.32, 132.18, 134.05, 135.83, 139.88, 148.30, 155.19, 157.97, 159.41, 170.31 and 175.20; and

g) Hydrate VI, wherein Hydrate VI is characterized by (i) an X-ray powder diffraction pattern obtained using copper K α radiation which comprises 2Θ values in degrees of about 20.5, 12.8, and 19.4; and/or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 4.87, 6.24, 11.70, 12.85, 18.36, 26.55, 28.31 m 31.51, 34.98, 38.47, 42.09, 54.27, 56.12, 60.10, 73.49, 73.97, 105.91, 108.04, 118.39, 119.75, 121.33, 129.96, 133.87, 136.13, 142.26, 142.97, 146.85, 148.36, 154.97, 157.32, 160.71, 168.23, 172.21 and 175.34 ppm.

2. A pharmaceutical composition comprising a therapeutically effect amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

3. A method of treating HCV in a patient comprising the step of administering to the patient a therapeutically effective amount of a compound of claim 1 .

4. A method of treating HCV in a patient, said method comprising administering an effective amount of a compound of claim 1 to the patient.

5. The compound of claim 1 for use in the treatment of HCV.

6. A method of making a compound of claim 1 , where said Compound A is Hydrate III, made by a process comprising crystallising Compound A using an acetone/water ratio of 80:20 v/v acetone to water to 0:100 v/v acetone to water and drying.

Assignments (3)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
CHANGE OF ADDRESS Recorded May 10, 2022
From: MERCK SHARP & DOHME (UK) LIMITED
To: MERCK SHARP & DOHME (UK) LIMITED
Reel/Frame 060110/0121 →
NUNC PRO TUNC ASSIGNMENT Recorded Aug 5, 2021
From: MERCK SHARP & DOHME LIMITED
To: MERCK SHARP & DOHME (UK) LIMITED
Reel/Frame 057089/0547 →