Anti-TGF-beta antibodies and their use

Patent metadata

Field	Value
Publication number	US-11242384-B2
Application number	US-202016931198-A
Country	US
Kind code	B2
Filing date	Jul 16, 2020
Priority date	Jan 20, 2017
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

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.

First claim

What is claimed is:

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 IgG 4 constant region having a proline at position 228 (EU numbering).

2. 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.

3. 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.

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

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

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

7. A pharmaceutical composition comprising the antibody of claim 6 and a pharmaceutically acceptable carrier.

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

9. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier.

10. An article of manufacture comprising the antibody of claim 8 and another therapeutic agent.

11. The article of manufacture of claim 10 , wherein the other therapeutic agent is an anti-PD-1 or anti-PD-L1 antibody.

12. The article of manufacture of claim 10 , 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.

13. The article of manufacture of claim 12 , 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.

14. The article of manufacture of claim 13 , 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.

Assignees

• Sanofi Sa

Inventors

• Shapiro Gary
• Brower Kevin
• Finn Patrick
• Gregory Richard C
• Koduri Rao
• Liu Feng
• Malkova Natalia
• Mankoo Parminder
• Pollard Jack R
• Qiu Huawei
• Theilhaber Joachim
• Winter Christopher
• Yu Marcella

Classifications

• C07K16/22 Primary

  against growth factors {; against growth regulators} · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title