# US 2023/0057519 A1 · Treatment of Ocular Diseases with Fully-Human Post-Translationally Modified Anti-VEGF Fab

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- Number: US 2023/0057519 A1
- Document ID: US20230057519A1
- Status: Published application
- Kind: A1
- Application number: 17/704,170
- Filed: 2022-03-25
- Published: 2023-02-23
- Earliest claimed: 2016-04-15
- Assignees: REGENXBIO Inc.
- Applicants: REGENXBIO Inc.
- Inventors: Curran Matthew Simpson; Stephen Yoo; Karen Fran Kozarsky; Rickey Robert Reinhardt; Laura A. Coruzzi
- Web page: https://patentgrep.com/patent/US20230057519A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- A61P 27/02: Ophthalmic agents
- C12N 15/86: Viral vectors
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/55: Fab or Fab'
- C07K 2317/622: Single chain antibody (scFv)
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2830/42: being an intron or intervening sequence for splicing and/or stability of RNA
- C12N 2830/50: regulating RNA stability, not being an intron, e.g. poly A signal
- C12N 2840/203: having an IRES
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) monoclonal antibody (“mAb”) or the antigen-binding fragment of a mAb against human vascular endothelial growth factor (“hVEGF”)—such as, e.g., a fully human-glycosylated (HuGly) anti-hVEGF antigen-binding fragment—to the retina/vitreal humour in the eye(s) of human subjects diagnosed with ocular diseases caused by increased neovascularization, for example, neovascular age-related macular degeneration (“nAMD”), also known as “wet” age-related macular degeneration (“WAMD”), age-related macular degeneration (“AMD”), and diabetic retinopathy.

## Claims

### Claim at position 1

1-7. (canceled)

### Claim 8

An anti-human vascular endothelial growth factor (hVEGF) antigen-binding fragment produced by human retinal cells.

### Claim 9 (depends on 8)

The anti-hVEGF antigen-binding fragment of claim 8, which is produced by human photoreceptor cells.

### Claim 10 (depends on 8)

The anti-hVEGF antigen-binding fragment of claim 8, which is glycosylated.

### Claim 11 (depends on 10)

The anti-hVEGF antigen-binding fragment of claim 10, which contains a α2,6-sialylated glycan.

### Claim 12 (depends on 10)

The anti-hVEGF antigen-binding fragment of claim 10, which does not contain NeuGc.

### Claim 13 (depends on 8)

The anti-hVEGF antigen-binding fragment of claim 8, which contains a tyrosine-sulfation.

### Claim 14 (depends on 8)

The anti-hVEGF antigen-binding fragment of claim 8, which is a Fab, F(ab′)2, or single chain variable domain (scFv).

### Claim 15 (depends on 8)

The anti-hVEGF antigen-binding fragment of claim 8, which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO. 1 or SEQ ID NO. 3, and a light chain comprising the amino acid sequence of SEQ ID NO. 2, or SEQ ID NO. 4.

### Claim 16 (depends on 8)

The anti-hVEGF antigen-binding fragment of claim 8, which comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 17-19 or SEQ ID NOs: 20, 18, and 21.

### Claim 17

A glycosylated anti-hVEGF antigen-binding fragment, which:
(a) contains a α2,6-sialylated glycan;
(b) does not contain NeuGc; and/or
(c) contains a tyrosine-sulfation.

### Claim 18 (depends on 17)

The glycosylated anti-hVEGF antigen-binding fragment of claim 17, which is a Fab, F(ab′)2, or single chain variable domain (scFv).

### Claim 19 (depends on 17)

The glycosylated anti-hVEGF antigen-binding fragment of claim 17, which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO. 1 or SEQ ID NO. 3, and a light chain comprising the amino acid sequence of SEQ ID NO. 2, or SEQ ID NO. 4.

### Claim 20 (depends on 17)

The glycosylated anti-hVEGF antigen-binding fragment of claim 17, which comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs:17-19 or SEQ ID NOs: 20, 18, and 21.

### Claim 21

An anti-hVEGF antigen-binding fragment, which contains a tyrosine-sulfation.

### Claim 22 (depends on 8)

A method of treating a human subject diagnosed with neovascular age-related macular degeneration (nAMD), comprising delivering to the retina of said human subject a therapeutically effective amount of the anti-hVEGF antigen-binding fragment of claim 8.

### Claim 23 (depends on 22)

The method of claim 22, wherein the anti-hVEGF antigen-binding fragment is expressed from an AAV8-based viral vector.

### Claim 24 (depends on 17)

A method of treating a human subject diagnosed with nAMD, comprising delivering to the retina of said human subject a therapeutically effective amount of the glycosylated anti-hVEGF antigen-binding fragment of claim 17.

### Claim 25 (depends on 24)

The method of claim 24, wherein the glycosylated anti-hVEGF antigen-binding fragment is expressed from an AAV8-based viral vector.

### Claim 26 (depends on 21)

A method of treating a human subject diagnosed with neovascular age-related macular degeneration (nAMD), comprising delivering to the retina of said human subject a therapeutically effective amount of the anti-hVEGF antigen-binding fragment of claim 21.

### Claim 27 (depends on 26)

The method of claim 26, wherein the anti-hVEGF antigen-binding fragment is expressed from an AAV8-based viral vector.

### Claim 28

A pharmaceutical composition suitable for subretinal administration comprising a suspension of a recombinant viral vector encoding an anti-hVEGF antigen-binding fragment in a formulation buffer comprising a physiologically compatible aqueous buffer and a surfactant wherein the recombinant viral vector in the composition is capable of transducing human retinal cells upon subretinal administration.

### Claim 29

A pharmaceutical composition suitable for subretinal administration comprising a suspension of a recombinant viral vector encoding an anti-hVEGF antigen-binding fragment in a formulation buffer comprising a physiologically compatible aqueous buffer and a surfactant wherein the recombinant viral vector in the composition is capable of transducing human retinal cells upon subretinal administration.

### Claim 30

A method of manufacturing a recombinant viral vector comprising providing a host cell stably transformed with sequences encoding an anti-hVEGF antigen-binding fragment, wherein the recombinant viral vector is capable of transducing human retinal cells upon subretinal administration.

### Claim 31

A method of manufacturing a recombinant viral vector comprising providing a host cell stably transformed with sequences encoding an anti-hVEGF antigen-binding fragment, wherein the recombinant viral vector is capable of transducing human retinal cells upon subretinal administration.