Crystalline forms of therapeutic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-10160765-B2
Application number	US-201715712645-A
Country	US
Kind code	B2
Filing date	Sep 22, 2017
Priority date	Nov 1, 2013
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

Described herein are 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 method of inhibiting aberrant vascular endothelial growth factor (VEGF) signaling comprising administering to a subject in need thereof a therapeutically effective amount of crystalline form A of 7-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinazolin-7-yloxy)propyl)-2-oxa-7-azaspiro[3.5]nonane 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 method of claim 1 , wherein crystalline Form A further has XRPD 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 method of claim 1 , wherein crystalline Form A has the XRPD pattern as shown in FIG. 1 .

4. The method of claim 1 , wherein the crystalline form is administered topically, by injection, to the eye, orally, or by inhalation.

5. The method of claim 1 , wherein the inhibition of aberrant VEGF signaling treats an ocular disease.

6. The method of claim 5 , wherein the ocular disease is retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, or retinal vein occlusion.

7. The method of claim 1 , wherein the aberrant signaling of VEGF is associated with cancer.

8. A method of inhibiting aberrant vascular endothelial growth factor (VEGF) signaling comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising:
a plurality of coated particles, comprising:
a core particle comprising crystalline form A of 7-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinazolin-7-yloxy)propyl)-2-oxa-7-azaspiro[3.5]nonane having an 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, 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.

9. The method of claim 8 , 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.

10. The method of claim 8 , wherein the crystalline form is administered topically, by injection, to the eye, orally, or by inhalation.

11. The method of claim 8 , wherein the inhibition of aberrant VEGF signaling treats an ocular disease.

12. The method of claim 11 , wherein the ocular disease is retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, or retinal vein occlusion.

13. The method of claim 8 , wherein the aberrant signaling of VEGF is associated with cancer.

14. The method of claim 1 , wherein the inhibition of VEGF signaling comprises inhibiting abnormal angiogenesis.

15. The method of claim 8 , wherein the inhibition of VEGF signaling comprises inhibiting abnormal angiogenesis.

Assignees

• Kala Pharmaceuticals Inc

Inventors

• Enlow Elizabeth
• Nguyen Minh Ngoc
• Ong Winston Z

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• 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

• A61P27/02

  Ophthalmic agents · CPC title

• C07D491/107 Primary

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title