# US 2021/0079080 A1 · Anti-vegf anitbodies and methods of use

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- Number: US 2021/0079080 A1
- Document ID: US20210079080A1
- Status: Published application
- Kind: A1
- Application number: 16/912,950
- Filed: 2020-06-26
- Published: 2021-03-18
- Earliest claimed: 2017-12-29
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Stefan Dengl; Sebastian Fenn; Guy Georges; Joerg Moelleken; Francesca Ros; Esther Koenigsberger
- Web page: https://patentgrep.com/patent/US20210079080A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39591: {Stabilisation, fragmentation}
- G16B 15/00: ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment
- G16C 20/50: Molecular design, e.g. of drugs
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE

## Abstract

The present invention relates to anti-VEGF antibodies and methods of their production and their use.

## Claims

### Claim 1 (depends on 2)

The antibody of claim 2,
a) wherein binding of the antibody to VEGF significantly inhibits VEGF-binding to VEGF receptor VEGF-R2 without significantly inhibiting VEGF-binding to VEGF receptor VEGF-R1, and
b) wherein the antibody binds VEGF with an affinity of ≤150 pM as measured by surface plasmon resonance at a temperature of 25° C. and as measured by surface plasmon resonance at a temperature of 37° C.

### Claim 2

An antibody that binds to VEGF, wherein the antibody comprises
a) a VH domain comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:03; (ii) CDR-H2 having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:04; and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:05; and
b) a VL domain comprising (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO:06; (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO:07; and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO:08.

### Claim 3 (depends on 2)

The antibody of claim 2 comprising:
(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO:04,
(b) CDR-H2 comprising the amino acid sequence selected from the group consisting of SEQ ID NO:04, SEQ ID NO:10, and SEQ ID NO: 12, and
(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO:05, and
wherein the antibody comprises a light chain variable domain (VL) comprising:
(d) CDR-L1 comprising the amino acid sequence of SEQ ID NO:06,
(e) CDR-L2 comprising the amino acid sequence of SEQ ID NO:07, and
(f) CDR-L3 comprising the amino acid sequence of SEQ ID NO:08.

### Claim 4 (depends on 2)

The antibody of claim 2, comprising a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:01; and a VL sequence of SEQ ID NO:02.

### Claim 5 (depends on 2)

The antibody of claim 2, comprising:
(a) a VH sequence of SEQ ID NO: 01 and a VL sequence of SEQ ID NO: 02,
(b) a VH sequence of SEQ ID NO: 09 and a VL sequence of SEQ ID NO: 02,
(c) a VH sequence of SEQ ID NO: 11 and a VL sequence of SEQ ID NO: 02,
(d) a VH sequence of SEQ ID NO: 33 and a VL sequence of SEQ ID NO: 02,
(e) a VH sequence of SEQ ID NO: 42 and a VL sequence of SEQ ID NO: 02, or
(f) a VH sequence of SEQ ID NO: 44 and a VL sequence of SEQ ID NO: 02.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The antibody of any one of claims 1 to 5, which is a Fab fragment.

### Claim 7 (depends on 2)

The antibody of claim 2, wherein the antibody binds to VEGF with an affinity of ≤150 pM as measured by surface plasmon resonance at a temperature of 25° C.

### Claim 8 (depends on 2)

The antibody of claim 2, wherein the antibody binds to the same epitope as an antibody comprising a VH sequence of SEQ ID NO: 01 and a VL sequence of SEQ ID NO: 02.

### Claim 9

An antibody that binds to VEGF that is an affinity matured variant of an antibody having a VH sequence of SEQ ID NO: 01 and a VL sequence of SEQ ID NO: 02.

### Claim 10

An antibody that binds to VEGF, wherein the antibody binds to the same epitope as an antibody having a VH sequence of SEQ ID NO: 01 and a VL sequence of SEQ ID NO: 02.

### Claim 11 (depends on 2, 3, 4, 5)

An isolated nucleic acid encoding the antibody of any one of claims 2 to 5.

### Claim 12 (depends on 11)

A host cell comprising the nucleic acid of claim 11.

### Claim 13 (depends on 12)

A method of producing an antibody that binds to VEGF comprising culturing the host cell of claim 12 under conditions suitable for the expression of the antibody.

### Claim 14 (depends on 1, 2, 3, 4, 5, 7, 8, 9, 10)

A pharmaceutical composition comprising the antibody of any one of claims 1 to 5 and 7 to 10 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, further comprising an additional therapeutic agent.

### Claim 16

(canceled)

### Claim 17

(canceled)

### Claim 18

(canceled)

### Claim 19

(canceled)

### Claim 20 (depends on 1, 2, 3, 4, 5, 7, 8, 9, 10)

A method of treating an individual having a VEGF-related disease comprising administering to the individual an effective amount of the antibody of any one of claims 1 to 5 and 7 to 10.

### Claim 21 (depends on 20)

The method of claim 20 further comprising administering an additional therapeutic agent to the individual.

### Claim 22 (depends on 1, 2, 3, 4, 5, 7, 8, 9, 10)

A method of inhibiting angiogenesis in an individual comprising administering to the individual an effective amount of the antibody of any one of claims 1 to 5 and 7 to 10 to inhibit angiogenesis.

### Claim 23 (depends on 14)

A method of treating an individual having a VEGF-related disease comprising administering to the individual an effective amount of the pharmaceutical composition of claim 14.

### Claim 24 (depends on 23)

The method of claim 23 further comprising administering an additional therapeutic agent to the individual.

### Claim 25 (depends on 14)

A method of inhibiting angiogenesis in an individual comprising administering to the individual an effective amount of the pharmaceutical composition of claim 14 to inhibit angiogenesis.

### Claim 26 (depends on 25)

The method of claim 25 further comprising administering an additional therapeutic agent to the individual.