Antibodies having specificity for btn2 and uses thereof

Patent metadata

Field	Value
Publication number	US-2020283519-A1
Application number	US-201816648886-A
Country	US
Kind code	A1
Filing date	Sep 21, 2018
Priority date	Sep 21, 2017
Publication date	Sep 10, 2020
Grant date	—

Abstract

The present invention relates to antibodies having specificity for BTN2 and uses thereof, in particular for the treatment of cancer.

First claim

1 . An anti-BTN2 antibody having specificity for human butyrophilin-2 (BTN2) characterized in that it has at least one of the following functions:
i. it inhibits production of IFN-γ and TNF-α of activated Vγ9/Vδ2 T cells, ii. it inhibits the cytolytic function of activated Vγ9/Vδ2 T cells, or iii. it inhibits the proliferation of activated Vγ9/Vδ2 T cells.

2 . The anti-BTN2 antibody of claim 1 , which has specificity for both human butyrophilin-2A1 (BTN2A1) and human butyrophilin-2A2 (BTN2A2).

3 . The anti-BTN2 antibody of claim 1 which competes for binding to BTN2A2 with at least one of the following reference murine antibodies:
i. mAb 4.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5231;
ii. mAb 5.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5232;
iii. mAb 7.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5233;
iv. mAb 7.48 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5234;
v. mAb 8.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5235; or
vi. mAb 8.16 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5236.

4 . The anti-BTN2A2 antibody of claim 1 , comprising,
i. the H-CDR1, H-CDR2, HCDR3, L-CDR1, L-CDR2 and L-CDR3 of the mAb 4.15 of SEQ ID NOs: 3-8 respectively; ii. the H-CDR1, H-CDR2, HCDR3, L-CDR1, L-CDR2 and L-CDR3 of the mAb 5.28 of SEQ ID NOs: 11-16 respectively; iii. the H-CDR1, H-CDR2, HCDR3, L-CDR1, L-CDR2 and L-CDR3 of the mAb 7.28 of SEQ ID NOs: 19-24 respectively; iv. the H-CDR1, H-CDR2, HCDR3, L-CDR1, L-CDR2 and L-CDR3 of the mAb 7.48 of SEQ ID NOs: 27-32 respectively; v. the H-CDR1, H-CDR2, HCDR3, L-CDR1, L-CDR2 and L-CDR3 of the mAb 8.15 of SEQ ID NOs: 35-40 respectively, or, vi. the H-CDR1, H-CDR2, HCDR3, L-CDR1, L-CDR2 and L-CDR3 of the mAb 8.16 of SEQ ID NOs: 43-48 respectively.

5 . The anti-BTN2 antibody of claim 1 , comprising,
i. a heavy chain wherein the VH region has at least 95% identity with SEQ ID NO:9 and a light chain wherein the VL region has at least 95% identity with SEQ ID NO:10; ii. a heavy chain wherein the VH region has at least 95% identity with SEQ ID NO:17 and a light chain wherein the VL region has at least 95% identity with SEQ ID NO:18; iii. a heavy chain wherein the VH region has at least 95% identity with SEQ ID NO:25 and a light chain wherein the VL region has at least 95% identity with SEQ ID NO:26; iv. a heavy chain wherein the VH region has at least 95% identity with SEQ ID NO:33 and a light chain wherein the VL region has at least 95% identity with SEQ ID NO:34; v. a heavy chain wherein the VH region has at least 95% identity with SEQ ID NO:41 and a light chain wherein the VL region has at least 95% identity with SEQ ID NO:42; or, vi. a heavy chain wherein the VH region has at least 95% identity with SEQ ID NO:49 and a light chain wherein the VL region has at least 95% identity with SEQ ID NO:50.

6 . The anti-BTN2 antibody of claim 1 , wherein the anti-BTN2 antibody does not cross-react with human CD277.

7 . The anti-BTN2 antibody of claim 1 , which inhibits the cytolytic function of Vγ9/Vδ2 T cells in the presence of the agonist anti-CD277 antibody mAb 20.1.

8 . The anti-BTN2 antibody of claim 1 , which is a human, chimeric or humanized antibody.

9 . A nucleic acid molecule which encodes a heavy chain and/or a light chain of the anti-BTN2 antibody of claim 1 .

10 . A host cell comprising the nucleic acid of claim 9 .

11 . (canceled)

12 . A method of treating an autoimmune or inflammatory disorder or transplant rejection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the anti-BTN2 antibody of claim 1 .

13 . A pharmaceutical composition comprising the anti-BTN2 antibody of claim 1 , and at least a pharmaceutically acceptable carrier.

14 . The method of claim 12 , wherein the autoimmune or inflammatory disorder is selected from the group consisting of: rheumatoid arthritis (RA), insulin dependent diabetes mellitus (Type 1 diabetes), multiple sclerosis (MS), Crohn's disease, systemic lupus erythematosus (SLE), scleroderma, Sjogren's syndrome, pemphigus vulgaris, pemphigoid, addison's disease, ankylosing spondylitis, aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, coeliac disease, dermatomyositis, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease, idiopathic leucopenia, idiopathic thrombocytopenic purpura, male infertility, mixed connective tissue disease, myasthenia gravis, pernicious anemia, phacogenic uveitis, primary biliary cirrhosis, primary myxoedema, Reiter's syndrome, stiff man syndrome, thyrotoxicosis, ulcertitive colitis, and Wegener's granulomatosis.

Assignees

• Imcheck Therapeutics Sas
• Inst Nat Sante Rech Med
• Inst Jean Paoli & Irene Calmettes
• Univ Aix Marseille
• Centre Nat Rech Scient

Inventors

• Olive Daniel
• Pasero Christine

Classifications

• C07K2317/75

  Agonist effect on antigen · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• A61K2039/505

  comprising antibodies · CPC title