JPWO2020025703A5 - - Google Patents

Claims (22)

An isolated anti-BTN3A antibody comprising the variable heavy chain polypeptide VH of SEQ ID NO:1 and the variable light chain polypeptide VL of SEQ ID NO:2 or SEQ ID NO:3. 2. The isolated anti-BTN3A antibody of claim 1, which binds to a human BTN3A polypeptide. 3. The isolated anti- _BTN3A antibody of claim 1 or 2, which binds a human _BTN3A polypeptide with a KD of 10 nM or less, preferably 5 nM or less, as measured by surface plasmon resonance. . said antibody induces activation of Vγ9Vδ2-T cells in co-culture with BTN3-expressing cells with an EC ₅₀ of less than 5 μg/ml, preferably 1 μg/ml or less, as measured in a degranulation assay; The isolated anti-BTN3A antibody of any one of claims 1-3. comprising a mutated or chemically modified IgG1 constant region, wherein said mutated or chemically modified IgG1 constant region enhances Fcγ receptor activity when compared to a corresponding antibody having a wild-type IgG1 isotype constant region 5. The isolated anti-BTN3A antibody of any one of claims 1-4, which does not bind or has reduced binding. 6. The isolated anti-BTN3A antibody of Claim 5, wherein said mutant IgGl constant region is the IgGl triple mutant L247F L248E and P350S. 7. The isolated anti-BTN3A antibody of any one of claims 1-6, which is a mAb1 comprising the heavy chain of SEQ ID NO:4 and the light chain of SEQ ID NO:6. 8. The isolated anti-BTN3A antibody of any one of claims 1-7 for use as (i) a therapeutic agent or (ii) as a diagnostic agent. A first pharmaceutical composition comprising the isolated anti-BTN3A antibody of any one of claims 1 to 7 and an anti-PD1 or anti-PD-L1 antibody, or IL-2 or IL-15, etc. A pharmaceutical composition kit for the treatment of cancer, comprising a second pharmaceutical composition comprising a cytokine or pegylated variant thereof. A first pharmaceutical composition comprising the isolated anti-BTN3A antibody of any one of claims 1-7, and a second pharmaceutical composition comprising an anti-PD1 antibody, wherein the anti-PD1 antibody is A pharmaceutical composition kit for the treatment of cancer, which is pembrolizumab. A method for treating cancer, comprising a first pharmaceutical composition comprising the isolated anti-BTN3A antibody of any one of claims 1 to 7, and a second pharmaceutical composition comprising IL-2. A pharmaceutical composition kit for 12. The pharmaceutical composition kit according to claim 10 or 11, wherein the anti-BTN3A antibody is mAb1 comprising the heavy chain of SEQ ID NO:4 and the light chain of SEQ ID NO:6. A pharmaceutical composition comprising an anti-BTN3A antibody in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier. 14. A pharmaceutical composition according to claim 13, optionally administered in combination with other active ingredients, for example anti-PD1 or anti-PD-L1 antibodies, or cytokines such as IL-2 or IL-15. 15. The pharmaceutical composition of claim 14, wherein said other active ingredient comprises an anti-PD1 antibody, and said anti-PD1 antibody is pembrolizumab. 15. A pharmaceutical composition according to claim 14, wherein said other active ingredient comprises IL-2. 17. The pharmaceutical composition of claim 15 or 16, wherein said anti-BTN3A antibody is mAb1 comprising the heavy chain of SEQ ID NO:4 and the light chain of SEQ ID NO:6. A lyophilized formulation, prefilled syringe or vial comprising the anti-BTN3A antibody of any one of claims 1-7. An expression vector for recombinant production of the anti-BTN3A antibody of any one of claims 1-7 in a host cell, the expression vector comprising at least one nucleic acid encoding said anti-BTN3A antibody. 20. The expression vector of claim 19 , comprising nucleic acids encoding at least the heavy and light chains of mAbl as defined in claim 7. A host cell comprising an expression vector according to claim 19 or 20 . Process for the production of an anti-BTN3A antibody according to any one of claims 1 to 7, comprising: (i) culturing the host cell according to claim 21 for expression of said antibody by the host cell optionally (ii) purifying said antibody; (iii) recovering said antibody.