# US 10,765,759 B2 · Methods of treating an ocular disease or disorder

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- Number: US 10,765,759 B2
- Document ID: US10765759B2
- Status: Granted
- Kind: B2
- Application number: 15/781,395
- Filed: 2016-12-08
- Published: 2018-11-08
- Granted: 2020-09-08
- Earliest claimed: 2015-12-09
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Kevin E. Healy; Eda Isil Altiok; David V. Schaffer; Wesley M. Jackson
- Web page: https://patentgrep.com/patent/US10765759B2

## CPC

- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 38/179: {for growth factors; for growth regulators}
- A61K 38/43: Enzymes; Proenzymes; Derivatives thereof
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/6903: {the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel}
- A61P 27/02: Ophthalmic agents
- C07K 16/22: against growth factors {; against growth regulators}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/35: Valency
- C07K 2317/622: Single chain antibody (scFv)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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.

### Claim 12 (depends on 1)

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