Crystalline forms of therapeutic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-9458169-B2
Application number	US-201414530092-A
Country	US
Kind code	B2
Filing date	Oct 31, 2014
Priority date	Nov 1, 2013
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

Described herein is certain crystalline forms of Compound 3, as well as pharmaceutical compositions employing the crystalline forms. Also provided are particles (e.g., nanoparticles) comprising such crystalline forms or pharmaceutical compositions. In certain examples, the particles are mucus penetrating particles (MPPs). The present invention further relates to methods of treating or preventing diseases using crystalline forms or pharmaceutical compositions.

First claim

What is claimed is:

1. A crystalline form of 7-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinazolin-7-yloxy)propyl)-2-oxa-7-azaspiro[3.5]nonane, wherein said crystalline form is crystalline Form A having an X-ray powder diffraction (XRPD) pattern with peaks at about 6.11, 9.63, 16.41, 18.60, 20.36 and 23.01±0.3 degrees two theta, or 14.45, 9.17, 5.40, 4.77, 4.36 and 3.86±0.3 Å in d-spacing.

2. The crystalline Form A of claim 1 , wherein said XRPD pattern further has peaks at about 11.46, 12.26, 18.16, 19.51, 21.12 and 25.71±0.3 degrees two theta or 7.71, 7.22, 4.88, 4.55, 4.20 and 3.46±0.3 Å in d-spacing.

3. The crystalline Form A of claim 1 , wherein said XRPD pattern further has peaks at about 11.10, 15.66, 17.54, 22.31, 24.79 and 28.90±0.3 degrees two theta or 7.96, 5.65, 5.05, 3.98, 3.59 and 3.09±0.3 Å in d-spacing.

4. The crystalline Form A of claim 1 , wherein said crystalline form has an XRPD pattern with peaks at about 6.11, 9.63, 11.10, 11.46, 12.26, 15.66, 16.41, 17.54, 18.16, 18.60, 19.51, 20.36, 21.12, 22.31, 23.01, 24.79, 25.71 and 28.90±0.3 degrees two theta or 14.45, 9.17, 7.96, 7.71, 7.22, 5.65, 5.40, 5.05, 4.88, 4.77, 4.55, 4.36, 4.20, 3.98, 3.86, 3.59, 3.46 and 3.09±0.3 Å in d-spacing.

5. The crystalline form A of claim 1 having the X-ray powder diffraction pattern as shown in FIG. 1 .

6. A process for preparing crystalline Form A of claim 1 , wherein said process comprising wet-milling a slurry comprising an amorphous form of 7-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinazolin-7-yloxy)propyl)-2-oxa-7-azaspiro[3.5]nonane and a non-ionic surfactant to obtain nanoparticles of crystalline Form A of the compound.

7. The process of claim 6 , wherein said XRPD pattern further has peaks at about 11.46, 12.26, 18.16, 19.51, 21.12 and 25.71±0.3 degrees two theta or 7.71, 7.22, 4.88, 4.55, 4.20 and 3.46±0.3 Å in d-spacing.

8. The process of claim 6 , wherein said XRPD pattern further has peaks at about 11.10, 15.66, 17.54, 22.31, 24.79 and 28.90±0.3 degrees two theta or 7.96, 5.65, 5.05, 3.98, 3.59 and 3.09±0.3 Å in d-spacing.

9. The process of claim 6 , wherein said crystalline Form A has an XRPD pattern with peaks at about 6.11, 9.63, 11.10, 11.46, 12.26, 15.66, 16.41, 17.54, 18.16, 18.60, 19.51, 20.36, 21.12, 22.31, 23.01, 24.79, 25.71 and 28.90±0.3 degrees two theta or 14.45, 9.17, 7.96, 7.71, 7.22, 5.65, 5.40, 5.05, 4.88, 4.77, 4.55, 4.36, 4.20, 3.98, 3.86, 3.59, 3.46 and 3.09±0.3 Å in d-spacing.

10. A pharmaceutical composition comprising the crystalline form A of claim 1 , said composition further comprising a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising:
a plurality of coated particles, comprising:
a core particle comprising a crystalline form A of claim 1 , wherein the crystalline form constitutes at least about 80 wt % of the core particle; and
a coating comprising one or more surface-altering agents surrounding the core particle.

12. The pharmaceutical composition of claim 11 , wherein the one or more surface-altering agents comprises a triblock copolymer comprising a hydrophilic block-hydrophobic block-hydrophilic block configuration, wherein the hydrophobic block has a molecular weight of at least about 2 kDa, and the hydrophilic blocks constitute at least about 15 wt % of the triblock copolymer.

13. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is suitable for topical administration.

14. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is suitable for injection.

15. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is suitable for delivery to the eye.

16. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is suitable for oral administration.

17. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is suitable for inhalation.

18. A method of treating an ocular disease comprising administering to a subject in need thereof a therapeutically effective amount of the crystalline form A of claim 1 .

19. The method of claim 18 , wherein the ocular disease is retinopathy.

20. The method of claim 18 , wherein the ocular disease is age-related macular degeneration (AMD).

21. The method of claim 18 , wherein the ocular disease is corneal neovascularization.

22. The method of claim 18 , wherein the ocular disease is diabetic macular edema.

23. The method of claim 18 , wherein the ocular disease is retinal vein occlusion.

Assignees

• Kala Pharmaceuticals Inc

Inventors

• Enlow Elizabeth
• Nguyen Minh Ngoc
• Ong Winston

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K9/146

  with organic macromolecular compounds · CPC title