# US 10,479,829 B2 · GARP-TGF-beta 1 antibodies

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- Number: US 10,479,829 B2
- Document ID: US10479829B2
- Status: Granted
- Kind: B2
- Application number: 15/977,449
- Filed: 2018-05-11
- Published: 2018-11-15
- Granted: 2019-11-19
- Earliest claimed: 2018-05-11
- Assignees: argenx BVBA; Université Catholique de Louvian
- Applicants: argenx BVBA; Université Catholique De Louvain
- Inventors: Sebastian Van der Woning; Filip Borgions; Torsten Dreier; Lore Mariën; Gitte De Boeck; Stéphanie Liénart; Sophie Lucas; Pierre Coulie
- Web page: https://patentgrep.com/patent/US10479829B2

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61K 2039/505: {comprising antibodies}
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/526: CH3 domain
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- 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)

## Abstract

The present invention relates to antibodies and antigen binding fragments thereof, which bind to a complex of GARP and TGF-β1, particularly a complex of human GARP and human TGF-β1. These antibodies and antigen binding fragments exhibit a combination of advantageous properties including high affinity antigen binding and the ability to inhibit the release of active TGF-β from regulatory T cells. The antibodies and antigen binding fragments of the present invention are relatively resistant to deamidation, isomerization and oxidation, such that they display improved stability.

## Claims

### Claim 1

A recombinant antibody or antigen binding fragment thereof, which binds to a complex of human glycoprotein A repetitions predominant (GARP) and TGF-β1, wherein the antibody or antigen binding fragment thereof comprises
a heavy chain variable domain (VH), wherein:
the VH CDR3 comprises the amino acid sequence YEWETVVVGDLMYEYEY (SEQ ID NO: 13),
the VH CDR2 comprises the amino acid sequence RIDPEDAGTKYAQKFQG (SEQ ID NO: 12), and
the VH CDR1 comprises the amino acid sequence SYYID (SEQ ID NO: 4); and
a light chain variable domain (VL), wherein:
the VL CDR3 comprises the amino acid sequence QQYASVPVT (SEQ ID NO: 11),
the VL CDR2 comprises the amino acid sequence GASRLKT (SEQ ID NO: 10), and
the VL CDR1 comprises the amino acid sequence QASQSISSYLA (SEQ ID NO: 9).

### Claim 2 (depends on 1)

The antibody or antigen binding fragment of claim 1, wherein the heavy chain variable domain (VH) comprises the amino acid sequence of SEQ ID NO: 14, and the light chain variable domain (VL) comprises the amino acid sequence of SEQ ID NO: 15.

### Claim 3 (depends on 1)

The antibody or antigen binding fragment of claim 1, further comprising the CH1 domain, hinge region, CH2 domain and/or CH3 domain of a human IgG.

### Claim 4 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the human IgG is IgG1.

### Claim 5 (depends on 3)

The antibody or antigen binding fragment of claim 3, wherein the human IgG is IgG4.

### Claim 6 (depends on 5)

The antibody or antigen binding fragment of claim 5, wherein the human IgG4 has the substitution S228P in the CH3 domain.

### Claim 7 (depends on 1)

An isolated polynucleotide which encodes the heavy chain variable domain of the antibody or antigen binding fragment of claim 1.

### Claim 8 (depends on 7)

The isolated polynucleotide of claim 7, which comprises the sequence of SEQ ID NO:18.

### Claim 9 (depends on 1)

An isolated polynucleotide which encodes the light chain variable domain of the antibody or antigen binding fragment of claim 1.

### Claim 10 (depends on 9)

The isolated polynucleotide of claim 9, which comprises the sequence of SEQ ID NO:19.

### Claim 11 (depends on 1)

An isolated polynucleotide which encodes the antibody or antigen binding fragment of claim 1.

### Claim 12 (depends on 11)

An expression vector comprising the polynucleotide of claim 11 operably linked to regulatory sequences which permit expression of the antibody, antigen binding fragment, heavy chain variable domain, or light chain variable domain in a host cell or cell-free expression system.

### Claim 13 (depends on 12)

A host cell or cell-free expression system containing the expression vector of claim 12.

### Claim 14 (depends on 13)

A method of producing a recombinant antibody or antigen binding fragment thereof,
comprising
culturing the host cell or cell-free expression system of claim 13 under conditions which permit expression of the antibody or antigen binding fragment; and
recovering the expressed antibody or antigen binding fragment.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising the antibody or antigen binding fragment according to claim 1 and at least one pharmaceutically acceptable carrier or excipient.

### Claim 16

A recombinant antibody, which binds to a complex of human glycoprotein A repetitions predominant (GARP) and TGF-β1, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 16, and a light chain comprising the amino acid sequence of SEQ ID NO: 17.