Methods for treating ocular disease using inhibitors of CSF-1R

Patent metadata

Field	Value
Publication number	US-10537563-B2
Application number	US-201716341075-A
Country	US
Kind code	B2
Filing date	Oct 13, 2017
Priority date	Oct 14, 2016
Publication date	Jan 21, 2020
Grant date	Jan 21, 2020

Abstract

The present invention provides in one aspect methods for treating ocular diseases by administering pharmaceutical compositions comprising an inhibitor of colony stimulating factor-1 (CSF-1) receptors. In another aspect, the present invention provides pharmaceutical compositions for treating ocular diseases, the compositions comprising at least one inhibitor of CSF-1R. The inhibitor can also be a selective inhibitor of CSF-1R in certain embodiments.

First claim

What is claimed is:

1. A method of treating an ocular disease or disorder that is mediated by CSF-1R comprising:
administering to a subject in need thereof an effective amount of Compound (I):

as a non-salt or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein said ocular disease or disorder is an ocular neovascular disease.

3. The method of claim 1 , wherein said ocular disease is selected from the group consisting of:
noninfectious uveitis, dry eye syndrome (Keratoconjunctivitis Sicca), corneal neovascularization, glaucoma, abnormal angiogenesis, choroidal neovascularization (CNV), retinal vascular permeability, retinal edema, diabetic retinopathy, diabetic macular edema, neovascular age-related macular degeneration (AMD), sequela associated with retinal ischemia, central retinal vein occlusion (CRVO), posterior segment neovascularization, polypoidal choroidal vasculopathy, proliferative vitreoretinopathy, anterior segment neovascularization, graft-versus-host disease, ocular tumors, corneal graft rejection, and uveitis.

4. The method of claim 1 , wherein Compound (I) or the pharmaceutically acceptable salt thereof is administered topically, intravitreally, intracamerally, orally, or intravenously.

5. The method of claim 1 , wherein Compound (I) or the pharmaceutically acceptable salt thereof is administered from 1 to 4 times daily.

6. The method of claim 1 , wherein the method further comprises administering an effective amount of an additional therapeutic agent selected from the group consisting of: bevacizumab, ranibizumab, aflibercept, pegpleranib, pegaptanib, conbercept, squalamine, abicipar pegol, PAN-90806, RTH258, (S)-5-(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)-N-(5-(1-methylcyclopropyl)-1H-pyrazol-3-yl)-1H-indole-1-carboxamide, 5-(6,7-dihydro-5H-pyrrolo[3,4 d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-methyl-cyclopropyl)-2H-pyrazol-3-yl]-amide, 5-(5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-methyl-cyclopropyl)-2H-pyrazol-3-yl]-amide, N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide and REGN2176-3.

7. The method of claim 1 , wherein Compound (I) comprises:

8. A method of treating diabetic retinopathy, diabetic macular edema, or age-related macular degeneration, in a mammalian subject suffering therefrom, said method comprising administering to the subject an effective amount of Compound (I):

as a non-salt or a pharmaceutically acceptable salt thereof in a pharmaceutical composition.

9. The method of claim 8 , wherein said composition is an ophthalmic composition.

10. The method of claim 9 , wherein said composition comprises from about 0.01 percent weight/volume to about 5 percent weight/volume of Compound (I).

11. The method of claim 9 , wherein said composition is a topical ophthalmic composition.

12. The method of claim 8 , wherein said composition is administered topically, intravitreally, intracamerally, orally, or intravenously.

13. The method of claim 8 , wherein said composition is an oral composition.

14. The method of claim 13 , wherein said oral composition comprises from 1 to 1000 mg of Compound (I).

15. The method of claim 8 , wherein said composition comprises:

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the subject is a human.

17. The method of claim 1 , wherein the Compound (I) is administered to the subject topically or orally.

18. The method of claim 1 , wherein the ocular disease or disorder is diabetic retinopathy, diabetic macular edema, or age-related macular degeneration.

19. The method of claim 8 , wherein the mammalian subject is a human.

Assignees

• Novartis Ag

Inventors

• Adams Christopher
• Mogi Muneto
• Poor Stephen Hedrick
• Ramsey Timothy Michael
• Wu Henry
• Zhang Qin

Classifications

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title