Anti-BTN3A antibodies and their use in treating cancer or infectious disorders

Patent metadata

Field	Value
Publication number	US-11945871-B2
Application number	US-202318327127-A
Country	US
Kind code	B2
Filing date	Jun 1, 2023
Priority date	Aug 1, 2018
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

The present invention relates to humanized antibodies that specifically bind to human BTN3A and their use in treating cancer and infectious disorders.

First claim

The invention claimed is:

1. An isolated anti-BTN3A antibody comprising a variable heavy chain polypeptide VH of SEQ ID NO:1 and a variable light chain polypeptide VL of SEQ ID NO:2.

2. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody binds to human BTN3A polypeptide with a K D of 10 nM or less as measured by surface plasmon resonance.

3. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody binds to human BTN3A polypeptide with a K D of 5 nM or less as measured by surface plasmon resonance.

4. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody induces activation of Vγ9Vδ2-T cells in co-culture with BTN3 expressing cells, with an EC 50 below 5 mg/ml as measured in a degranulation assay.

5. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody induces activation of Vγ9Vδ2-T cells in co-culture with BTN3 expressing cells, with an EC 50 below 1 mg/ml as measured in a degranulation assay.

6. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody comprises a silenced mutant IgG1 constant region.

7. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody comprises a IgG1 mutant Fc region with the following three amino acid substitutions: L247F, L248E, and P350S.

8. The isolated anti-BTN3A antibody of claim 1 , wherein the antibody comprises a heavy chain of SEQ ID NO:4 and a light chain of SEQ ID NO:6.

9. A pharmaceutical composition comprising an anti-BTN3A antibody of claim 1 , in combination with one or more of an agent selected from the group consisting of a pharmaceutically acceptable excipient, diluent and carrier.

10. A lyophilisate formulation, a pre-filled syringe or a vial comprising an anti-BTN3A antibody according to claim 1 .

11. An expression vector for the recombinant production of an anti-BTN3A antibody of claim 1 in a host cell, comprising at least one nucleic acid encoding the heavy variable chain of SEQ ID NO:1 and a nucleic acid encoding the light variable chain of SEQ ID N:2 of said anti-BTN3A antibody.

12. The expression vector of claim 11 , comprising a nucleic acid of SEQ ID NO:9 and a nucleic acid of SEQ ID NO:10 encoding respectively the heavy and light chains of said anti-BTN3A antibody.

13. A mammalian host cell comprising an expression vector according to claim 11 .

14. A process for the manufacturing of an anti-BTN3A antibody, comprising: (i) culturing the host cell of claim 13 for expression of said antibody by the host cell; optionally (ii) purifying said antibody; and (iii) recovering the antibody.

Assignees

• Imcheck Therapeutics Sas
• Inst Nat Sante Rech Med
• Univ Aix Marseille
• Inst Jean Paoli & Irene Calmette
• Centre National De La Rech Scientifique—Cnrs
• Univ Aix Marseille

Inventors

• Truneh Alemseged
• Olive Daniel
• Pasero Christine
• De Gassart Aude

Classifications

• A61K40/421

  Immunoglobulin superfamily · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/59

  Reproductive system, e.g. uterus, ovaries, cervix or testes · CPC title

• A61K2239/58

  Prostate · CPC title

• A61K2239/50

  Colon · CPC title