JPWO2020159368A5 - - Google Patents

Claims (40)

A multispecific antibody comprising a first antigen binding region capable of binding human CD40 and a second antigen binding region capable of binding human Vy9V52 T cell receptor. 2. The multispecific antibody of claim 1, which is a bispecific antibody. 3. The multispecific antibody according to claim 1 or 2, wherein said first antigen binding region is a single domain antibody. 4. The multispecific antibody of any one of claims 1-3, wherein said second antigen binding region is a single domain antibody. 5. The multispecific antibody according to any one of claims 1 to 4, wherein said first antigen binding region and second antigen binding region are covalently linked via a peptide linker. 6. The multispecific antibody of claim 5, wherein said peptide linker comprises or consists of the sequence shown in SEQ ID NO:21. 7. The multispecific antibody of any one of claims 1-6, wherein said first antigen binding region is located N-terminal to said second antigen binding region. 8. The multispecific antibody of any one of claims 1-7, which binds CD40 monovalently and binds human Vy9V52 T cell receptor monovalently. 9. The multispecific antibody of any one of claims 1-8, which is not an agonist of human CD40. 10. The multispecific antibody of any one of claims 1-9, which is an antagonist of human CD40. 11. The multispecific antibody of any one of claims 1-10, capable of sensitizing human CD40-expressing cells to venetoclax. 11. Competes with an antibody having the sequence shown in SEQ ID NO: 13 for binding to human CD40 and/or competes with an antibody having the sequence shown in SEQ ID NO: 14 for binding to human CD40 The multispecific antibody according to any one of . from claim 1, which binds to the same epitope on human CD40 as the antibody having the sequence shown in SEQ ID NO: 13 or binds to the same epitope on human CD40 as the antibody having the sequence shown in SEQ ID NO: 14 13. The multispecific antibody according to any one of 12. The first antigen-binding region is
- VH CDR1 sequence shown in SEQ ID NO: 1, VH CDR2 sequence shown in SEQ ID NO: 2, and VH CDR3 sequence shown in SEQ ID NO: 3, or - VH CDR1 sequence shown in SEQ ID NO: 4, shown in SEQ ID NO: 5 14. The multispecific antibody of any one of claims 1-13, comprising the VH CDR2 sequence and the VH CDR3 sequence shown in SEQ ID NO:6. 15. The multispecific antibody of any one of claims 1-14, wherein said first antigen binding region is humanized. The first antigen-binding region is
- the sequence shown in SEQ ID NO: 13 or the sequence shown in SEQ ID NO: 14, or - at least 90%, such as at least 92%, such as at least 94%, such as at least 96%, with the sequence shown in SEQ ID NO: 13, For example, a sequence having at least 98% sequence identity, or at least 90%, such as at least 92%, such as at least 94%, such as at least 96%, such as at least 98%, with the sequence shown in SEQ ID NO: 14 16. The multispecific antibody of any one of claims 1-15, comprising or consisting of a sequence having a sequence identity of . 17. The multispecific antibody of any one of claims 1-16, which is capable of activating human Vy9V52 T cells. 18. The multiplex of any one of claims 1-17, capable of mediating killing of human CD40-expressing cells from chronic lymphocytic leukemia patients and/or human CD40-expressing cells from multiple myeloma patients. specific antibody. 19. The multispecific antibody of any one of claims 1-18, which is capable of mediating killing of CD40L-stimulated human CD40-expressing cells from patients with chronic lymphocytic leukemia. 20. The multispecific antibody of any one of claims 1-19, which is capable of binding to human V[delta]2. of claims 1 to 20, which competes for binding to human Vδ2 with an antibody having the sequence shown in SEQ ID NO: 17, or competes with an antibody having the sequence shown in SEQ ID NO: 18 for binding to human Vδ2 A multispecific antibody according to any one of paragraphs. from claim 1, which binds to the same epitope on human Vδ2 as the antibody having the sequence shown in SEQ ID NO: 17 or binds to the same epitope on human Vδ2 as the antibody having the sequence shown in SEQ ID NO: 18 22. The multispecific antibody according to any one of 21. The second antigen-binding region comprises the VH CDR1 sequence shown in SEQ ID NO:7, the VH CDR2 sequence shown in SEQ ID NO:8, and the VH CDR3 sequence shown in SEQ ID NO:9, or is shown in SEQ ID NO:10 23. The multispecific antibody of any one of claims 1-22, comprising a VH CDR1 sequence, a VH CDR2 sequence as set forth in SEQ ID NO:11, and a VH CDR3 sequence as set forth in SEQ ID NO:12. 24. The multispecific antibody of any one of claims 1-23, wherein said second antigen binding region is humanized. The second antigen-binding region is
- the sequence shown in SEQ ID NO: 17, or - at least 90%, such as at least 92%, such as at least 94%, such as at least 96%, such as at least 98% sequence identity with the sequence shown in SEQ ID NO: 17 or a sequence selected from the group consisting of SEQ ID NOs: 25, 26, 27, 28, 29, 30, 31, 32, 33 and 34. A multispecific antibody according to any one of paragraphs. The first antigen-binding region is
- VH CDR1 sequence shown in SEQ ID NO: 1, VH CDR2 sequence shown in SEQ ID NO: 2, and VH CDR3 sequence shown in SEQ ID NO: 3, or - VH CDR1 sequence shown in SEQ ID NO: 4, shown in SEQ ID NO: 5 comprising a VH CDR2 sequence and a VH CDR3 sequence represented by SEQ ID NO: 6, wherein the second antigen-binding region comprises a VH CDR1 sequence represented by SEQ ID NO: 7, a VH CDR2 sequence represented by SEQ ID NO: 8, and SEQ ID NO: 9 26. The multispecific antibody of any one of claims 1-25, comprising a VH CDR3 sequence designated as: An antibody comprising a first antigen-binding region capable of binding to human CD40, which competes with an antibody having the sequence shown in SEQ ID NO: 13 for binding to human CD40 and/or binds to human CD40 An antibody that competes with the antibody having the sequence shown in SEQ ID NO: 14 for 28. Binds to the same epitope on human CD40 as the antibody having the sequence shown in SEQ ID NO: 13, or binds to the same epitope on human CD40 as the antibody having the sequence shown in SEQ ID NO: 14. Antibodies as indicated. The first antigen-binding region is
- VH CDR1 sequence shown in SEQ ID NO: 1, VH CDR2 sequence shown in SEQ ID NO: 2, and VH CDR3 sequence shown in SEQ ID NO: 3, or - VH CDR1 sequence shown in SEQ ID NO: 4, shown in SEQ ID NO: 5 29. The antibody of claim 27 or 28, comprising the VH CDR2 sequence and the VH CDR3 sequence shown in SEQ ID NO:6. The first antigen-binding region is
- the sequence shown in SEQ ID NO: 13 or the sequence shown in SEQ ID NO: 14, or - at least 90%, such as at least 92%, such as at least 94%, such as at least 96%, with the sequence shown in SEQ ID NO: 13, For example, a sequence having at least 98% sequence identity, or at least 90%, such as at least 92%, such as at least 94%, such as at least 96%, such as at least 98%, with the sequence shown in SEQ ID NO: 14 30. The antibody of any one of claims 27-29, comprising or consisting of a sequence having the sequence identity of 31. The antibody of any one of claims 27-30, wherein said first antigen binding region is a single domain antibody. A pharmaceutical composition comprising the multispecific antibody of any one of claims 1 to 26 or the antibody of any one of claims 27 to 31 and a pharmaceutically acceptable excipient thing. 32. A multispecific antibody according to any one of claims 1 to 26, or an antibody according to any one of claims 27 to 31, for use as a medicament. 32. A multispecific antibody according to any one of claims 1 to 26, or an antibody according to any one of claims 27 to 31, for use in treating cancer. Chronic lymphocytic leukemia, multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, follicular lymphoma, head and neck cancer, pancreatic cancer, ovarian cancer, lung cancer, breast cancer, colon cancer, prostate cancer, B-cell lymphoma / A multispecific antibody according to any one of claims 1 to 26, or any one of claims 27 to 31, for use in the treatment of leukemia, Burkitt's lymphoma or B-cell acute lymphoblastic leukemia or the antibody according to item 1. 27. A multispecific antibody according to any one of claims 1-26 for use in the treatment of chronic lymphocytic leukemia or multiple myeloma. A multispecific antibody according to any one of claims 1 to 26 or any one of claims 27 to 31, for use as defined in any one of claims 33 to 36 12. A multispecific antibody or antibodies according to claim 1, wherein said use is in combination with a Bcl-2 blocker, eg venetoclax. 32. A nucleic acid construct encoding the multispecific antibody of any one of claims 1-26 or the antibody of any one of claims 27-31. 39. An expression vector comprising the nucleic acid construct of claim 38 . 40. A host cell comprising the nucleic acid construct of claim 38 or the expression vector of claim 39 .