Valbenazine salts and polymorphs thereof

Patent metadata

Field	Value
Publication number	US-10065952-B2
Application number	US-201615338214-A
Country	US
Kind code	B2
Filing date	Oct 28, 2016
Priority date	Oct 30, 2015
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

Provided herein are salts of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester in amorphous and crystalline forms, and processes of preparation, and pharmaceutical compositions thereof. Also provided are methods of their use for treating, preventing, or ameliorating one or more symptoms of neurological disorders and diseases including hyperkinetic movement disorders or diseases.

First claim

What is claimed is:

1. A crystal form of the compound of Formula I:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of:
a) 6.3, 17.9, and 19.7°±0.2°; or of:
b) 6.3, 18.3, and 19.8°±0.2°.

2. A crystal form of the compound of Formula I:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of 5.7, 15.3, and 22.5°±0.2°.

3. A crystal form of the compound of Formula I:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of 6.2, 10.4, and 20.2°±0.2°.

4. A crystal form of the compound of Formula I:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of 6.7, 7.9, and 23.7°±0.2°.

5. A crystal form of the compound of Formula I:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of 6.8, 5.4 and 8.0°±0.2°.

6. Amorphous:

having an X-Ray diffraction pattern substantially as shown in FIG. 19 .

7. A crystal form of the compound of Formula II:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of 7.2, 9.2, and 18.0°±0.2°.

8. A crystal form of the compound of Formula II:

having an XRPD pattern comprising X-Ray diffraction peaks at two-theta angles of 4.8, 13.3, and 24.9°±0.2°.

9. Amorphous:

having an X-Ray diffraction pattern substantially as shown in FIG. 26 .

10. A pharmaceutical composition comprising the crystal form of claim 1 and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 , wherein the composition is formulated for oral administration.

12. The pharmaceutical composition of claim 10 , wherein the composition is formulated as a single dosage form.

13. A method of ameliorating one or more symptoms of a hyperkinetic disorder, comprising administering the crystal form of claim 1 .

14. The method according to claim 13 , wherein the hyperkinetic disorder is Huntington's disease, tardive dyskinesia, Tourette's syndrome, dystonia, hemiballismus, chorea, or tics.

15. The method according to claim 14 , wherein the hyperkinetic disorder is tardive dyskinesia.

16. The method according to claim 14 , wherein the hyperkinetic disorder is Tourette's syndrome.

17. A method for inhibiting vesicular monoamine transporter isoform 2 in a subject comprising administering to the subject the crystal form of claim 1 .

Assignees

• Neurocrine Biosciences Inc

Inventors

• Mcgee Kevin
• ZOOK Scott
• Carr Andrew
• Bonnaud Thierry

Classifications

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title