Crystalline forms of therapeutic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-11713323-B2
Application number	US-202117197702-A
Country	US
Kind code	B2
Filing date	Mar 10, 2021
Priority date	Nov 1, 2013
Publication date	Aug 1, 2023
Grant date	Aug 1, 2023

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±0.3, 9.63±0.3, 9.87±0.3, 11.10±0.3, 11.46±0.3, 12.26±0.3, 12.88±0.3, 14.40±0.3, 15.45±0.3, 15.66±0.3, 16.41±0.3, 17.54±0.3, 18.16±0.3, 18.60±0.3, 19.51±0.3, 20.36±0.3, 21.12±0.3, 21.14±0.3, 22.31±0.3, 23.01±0.3, 24.79±0.3, 25.71±0.3, 26.84±0.3, and 28.90±0.3 degrees two theta.

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

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

4. The method of claim 3 , wherein the ocular disease is retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, or retinal vein occlusion.

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

6. 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 7.70±0.3, 13.53±0.3, 9.87±0.3, 10.69±0.3, 12.88±0.3, 14.40±0.3, 15.45±0.3, 16.42±0.3, 17.27±0.3, 18.44±0.3, 18.90±0.3, 19.73±0.3, 21.14±0.3, 22.56±0.3, 23.10±0.3, 26.07±0.3, 26.84±0.3, and 29.12±0.3 degrees two theta.

7. The method of claim 6 , wherein the crystalline form is administered topically, by injection, to the eye, orally, or by inhalation.

8. The method of claim 6 , wherein the inhibition of aberrant VEGF signaling treats an ocular disease.

9. The method of claim 3 , wherein the ocular disease is retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, or retinal vein occlusion.

10. The method of claim 6 , wherein the aberrant signaling of VEGF is associated with cancer.

Assignees

• Kala Pharmaceuticals Inc

Inventors

• Enlow Elizabeth
• Nguyen Minh Ngoc
• Ong Winston Z

Classifications

• C07D491/107 Primary

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

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• A61K9/146

  with organic macromolecular compounds · CPC title