# US 2020/0399358 A1 · Anti-tgf-beta antibodies and their use

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- Number: US 2020/0399358 A1
- Document ID: US20200399358A1
- Status: Published application
- Kind: A1
- Application number: 16/931,198
- Filed: 2020-07-16
- Published: 2020-12-24
- Earliest claimed: 2017-01-20
- Assignees: Sanofi
- Applicants: Sanofi
- Inventors: Gary Shapiro; Kevin Brower; Patrick Finn; Richard C. Gregory; Rao Koduri; Feng Liu; Natalia Malkova; Parminder Mankoo; Jack R. Pollard; Huawei Qiu; Joachim Theilhaber; Christopher Winter; Marcella Yu
- Web page: https://patentgrep.com/patent/US20200399358A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/30: from tumour cells
- C07K 16/32: against translation products of oncogenes
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- 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: 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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 invention provides an improved pan-TGF-β antibody for treatment of conditions that are mediated by TGF-β, including autoimmune diseases, fibrotic conditions, and cancers. Also provided are methods and uses of the antibody in conjunction with other immunomodulatory agents such as an anti-PD-1 antibody.

## Claims

### Claim 1

An isolated monoclonal antibody that binds specifically to human TGF-β1, TGF-β2, and TGF-β3, comprising the heavy chain complementarity-determining regions (CDR) 1-3 in SEQ ID NO:1 and the light chain CDR1-3 in SEQ ID NO:2, wherein the antibody comprises a human IgG4 constant region having a proline at position 228 (EU numbering).

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain (VH) amino acid sequence corresponding to residues 1-120 of SEQ ID NO:1 and a light chain variable domain (VL) amino acid sequence corresponding to residues 1-108 of SEQ ID NO:2.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein the antibody has one or more of the following properties:
a) inhibits the differentiation of CD4+ T cells into inducible regulatory T cells (iTreg);
b) increases CD8+ T cell proliferation;
c) increases clustering of natural killer (NK) cells;
d) increases the level of MIP-2; and
e) increases the level of KC/GRO.

### Claim 4 (depends on 1)

A composition comprising the antibody of claim 1, wherein the composition comprises less than 1% of half antibody.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

A method of producing a pharmaceutical composition, comprising:
providing the antibody of claim 1; and
admixing the antibody with a pharmaceutically acceptable carrier.

### Claim 7 (depends on 1)

A nucleic acid molecule encoding the heavy chain, or encoding both the heavy and light chains, of the antibody of claim 1.

### Claim 8 (depends on 7)

A vector comprising the nucleic acid molecule of claim 7.

### Claim 9 (depends on 1)

A mammalian host cell comprising nucleotide sequences encoding both the heavy and light chains of the antibody of claim 1.

### Claim 10 (depends on 9)

A method of producing an antibody, comprising
culturing the mammalian host cell of claim 9 under conditions that allow expression of the nucleotide sequences; and
isolating the antibody from the culture.

### Claim 11

An isolated monoclonal antibody, wherein the amino acid sequences of the heavy and light chains comprise SEQ ID NOs:1 and 2, respectively.

### Claim 12 (depends on 11)

A pharmaceutical composition comprising the antibody of claim 11 and a pharmaceutically acceptable carrier.

### Claim 13 (depends on 11)

A method of producing a pharmaceutical composition, comprising:
providing the antibody of claim 11; and
admixing the antibody with a pharmaceutically acceptable carrier.

### Claim 14 (depends on 11)

A nucleic acid molecule encoding the heavy chain, or encoding both the heavy and light chains, of the antibody of claim 11.

### Claim 15 (depends on 14)

A vector comprising the nucleic acid molecule of claim 14.

### Claim 16 (depends on 11)

A mammalian host cell comprising nucleotide sequences encoding both the heavy and light chains of the antibody of claim 11.

### Claim 17 (depends on 16)

A method of producing an antibody, comprising
culturing the mammalian host cell of claim 16 under conditions that allow expression of the nucleotide sequences; and
isolating the antibody from the culture.

### Claim 18

An isolated monoclonal antibody, wherein the amino acid sequences of the heavy and light chains are SEQ ID NOs:1 and 2, respectively.

### Claim 19 (depends on 18)

A pharmaceutical composition comprising the antibody of claim 18 and a pharmaceutically acceptable carrier.

### Claim 20 (depends on 18)

A method of producing a pharmaceutical composition, comprising:
providing the antibody of claim 18; and
admixing the antibody with a pharmaceutically acceptable carrier.

### Claim 21 (depends on 18)

A nucleic acid molecule encoding the heavy chain, or encoding both the heavy and light chains, of the antibody of claim 18.

### Claim 22 (depends on 21)

A vector comprising the nucleic acid molecule of claim 21.

### Claim 23 (depends on 18)

A mammalian host cell comprising nucleotide sequences encoding the heavy and light chains of the antibody of claim 18.

### Claim 24 (depends on 23)

A method of producing an antibody, comprising
culturing the mammalian host cell of claim 23 under conditions that allow expression of the nucleotide sequences; and
isolating the antibody from the culture.

### Claim 25 (depends on 18)

An article of manufacture comprising the antibody of claim 18 and another therapeutic agent.

### Claim 26 (depends on 25)

The article of manufacture of claim 25, wherein the other therapeutic agent is an anti-PD-1 or anti-PD-L1 antibody.

### Claim 27 (depends on 25)

The article of manufacture of claim 25, wherein the other therapeutic agent is an anti-PD-1 antibody comprising the heavy chain CDR1-3 in SEQ ID NO:5 and the light chain CDR1-3 in SEQ ID NO:6.

### Claim 28 (depends on 27)

The article of manufacture of claim 27, wherein the anti-PD-1 antibody comprises a VH amino acid sequence corresponding to residues 1-117 of SEQ ID NO:5 and a VL amino acid sequence corresponding to residues 1-107 of SEQ ID NO:6.

### Claim 29 (depends on 28)

The article of manufacture of claim 28, wherein the amino acid sequences of the heavy and light chains of the anti-PD-1 antibody comprise SEQ ID NOs:5 and 6, respectively.

### Claim 30 (depends on 18)

A method of treating cancer in a patient in need thereof, comprising administering a therapeutically effectively amount of the antibody of claim 18 to the patient.