Methods of treating an ocular disease or disorder

Patent metadata

Field	Value
Publication number	US-10765759-B2
Application number	US-201615781395-A
Country	US
Kind code	B2
Filing date	Dec 8, 2016
Priority date	Dec 9, 2015
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

The present disclosure provides methods of treating an ocular disease or disorder. The methods involve direct administration into the eye of a conjugate comprising a biologically active polypeptide and a biocompatible polymer.

First claim

What is claimed is:

1. A method of treating an ocular disease or disorder in an individual, the method comprising administering to the individual an effective amount of a conjugate comprising:
a) a biologically active polypeptide having a molecular weight of from about 5 kDa to about 250 kDa, wherein the biologically active polypeptide is a single-chain Fv (scFv) anti-vascular endothelial growth factor (VEGF) antibody or a single-domain camelid (VHH) anti-VEGF antibody; and
b) a biocompatible polymer comprising hyaluronic acid having a molecular weight of from about 500 kDa to about 1 MDa,
wherein the polypeptide is covalently linked to the polymer directly or via a linker, and wherein the molar ratio of the biologically active polypeptide to the polymer is at least 25:1,
wherein said administering is by intravitreal administration.

2. The method of claim 1 , wherein the molar ratio of the biologically active polypeptide to the polymer is from 25:1 to 50:1.

3. The method of claim 1 , wherein the vitreous half-life of the conjugate is at least 7 days.

4. The method of claim 1 , wherein the individual is a human.

5. The method of claim 1 , wherein the ocular disorder is macular degeneration, choroidal neovascularization, retinal neovascularization, proliferative vitreoretinopathy, glaucoma, or ocular inflammation.

6. The method of claim 1 , wherein the conjugate is administered once every two months, once every three months, once every 6 months, or once a year.

7. The method of claim 1 , wherein the vitreous half-life of the conjugate is at least 5-fold greater than the half-life of the biologically active polypeptide not conjugated to the biocompatible polymer.

8. The method of claim 1 , wherein the vitreous half-life of the conjugate is from about one week to about 2 weeks.

9. The method of claim 1 , wherein
a) the biologically active polypeptide is a VHH anti-VEGF antibody; and
b) the biocompatible polymer comprises hyaluronic acid having a molecular weight of from 750 kDa to 1 MDa,
wherein the polypeptide is covalently linked to the polymer directly or via a linker, and
wherein the molar ratio of the biologically active polypeptide to the polymer is at least 25:1.

10. The method of claim 1 , wherein
a) the biologically active polypeptide is a VHH anti-VEGF antibody; and
b) the biocompatible polymer comprises hyaluronic acid having a molecular weight of from 750 kDa to 1 MDa,
wherein the polypeptide is covalently linked to the polymer directly or via a linker, and
wherein the molar ratio of the biologically active polypeptide to the polymer is at least 40:1.

11. The method of claim 1 , wherein
a) the biologically active polypeptide is a VHH anti-VEGF antibody; and
b) the biocompatible polymer comprises hyaluronic acid having a molecular weight of from 750 kDa to 1 MDa,
wherein the polypeptide is covalently linked to the polymer directly or via a linker, and
wherein the molar ratio of the biologically active polypeptide to the polymer is from 40:1 to 60:1.

12. The method of claim 1 , wherein the vitreous half-life of the conjugate is from about 2 weeks to about 4 weeks.

Assignees

• Univ California

Inventors

• Healy Kevin E
• Altiok Eda Isil
• Schaffer David V
• Jackson Wesley M

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P27/02

  Ophthalmic 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

• A61K2039/505

  comprising antibodies · CPC title