JPWO2020018820A5 - - Google Patents

Claims (17)

An isolated bispecific antigen binding molecule comprising
(a) a heavy chain variable region (HCVR) comprising HCDR1, HCDR2, HCDR3 domains comprising the first antigen binding domain amino acid sequences of SEQ ID NOs: 68, 70, 72, respectively, and amino acids of SEQ ID NOs: 84, 86, 88; a first antigen-binding domain that specifically binds human B-cell maturation antigen (BCMA), comprising a light chain variable region (LCVR) comprising LCDR1, LCDR2, LCDR3 domains, each comprising a sequence; and (b) a sequence HCVRs comprising HCDR1, HCDR2, HCDR3 domains comprising the amino acid sequences of numbers 92, 94, 96, respectively; , a second antigen-binding domain that specifically binds to human CD3;
The isolated bispecific antigen binding molecule comprising: An isolated bispecific antigen binding molecule comprising
(a) a heavy chain variable region (HCVR) comprising HCDR1, HCDR2, HCDR3 domains comprising the first antigen binding domain amino acid sequences of SEQ ID NOs: 68, 70, 72, respectively, and amino acids of SEQ ID NOs: 84, 86, 88; a first antigen-binding domain that specifically binds to human B-cell maturation antigen (BCMA), comprising a light chain variable region (LCVR) comprising LCDR1, LCDR2, LCDR3 domains, each comprising a sequence; and (b) a sequence HCVRs comprising HCDR1, HCDR2, HCDR3 domains comprising the amino acid sequences of numbers 100, 102, 104, respectively; , a second antigen-binding domain that specifically binds to human CD3;
The isolated bispecific antigen binding molecule comprising: (a) a first antigen binding domain comprising an HCVR comprising the amino acid sequence of SEQ ID NO:66 and an LCVR comprising the amino acid sequence of SEQ ID NO:82; and (b) an HCVR comprising the amino acid sequence of SEQ ID NO:90, and a second antigen-binding domain comprising an LCVR comprising the amino acid sequence of SEQ ID NO:82;
2. The isolated bispecific antigen binding molecule of claim 1, comprising: (a) a first antigen binding domain comprising an HCVR comprising the amino acid sequence of SEQ ID NO:66 and an LCVR comprising the amino acid sequence of SEQ ID NO:82; and (b) an HCVR comprising the amino acid sequence of SEQ ID NO:98, and a second antigen-binding domain comprising an LCVR comprising the amino acid sequence of SEQ ID NO:82;
3. The isolated bispecific antigen binding molecule of claim 2, comprising: 5. The isolated bispecific antigen-binding molecule of any one of claims 1-4, which is a bispecific antibody. (a) said bispecific antibody comprises a human IgG heavy chain constant region; optionally said human IgG heavy chain constant region is of isotype IgG1 or IgG4; and/or (b) said bispecific the antibody comprises a chimeric hinge that has reduced Fcγ receptor binding compared to a wild-type hinge of the same isotype;
6. The isolated bispecific antigen binding molecule of claim 5. A pharmaceutical composition comprising the bispecific antigen binding molecule of any one of claims 1-6 and a pharmaceutically acceptable carrier or diluent. A nucleic acid molecule comprising a nucleotide sequence encoding the bispecific antigen binding molecule of any one of claims 1-6, or the bispecific of any one of claims 1-6. A group of nucleic acid molecules comprising nucleotide sequences encoding the HCVR of the first antigen-binding domain, the HCVR of the second antigen-binding domain, and the LCVR of the first and second antigen-binding domains, respectively, of an antigen-binding molecule . An expression vector comprising a nucleic acid molecule according to claim 8 or a group of expression vectors each comprising a group of nucleic acid molecules according to claim 8. A bispecific antigen binding molecule according to any one of claims 1 to 6, a nucleic acid molecule or group of nucleic acid molecules according to claim 8, or an expression vector or group of expression vectors according to claim 9. host cells. 8. The pharmaceutical composition of claim 7, for inhibiting the growth of plasma cell tumors in a subject. 12. The pharmaceutical composition of claim 11, wherein said plasma cell neoplasm is multiple myeloma. 8. The pharmaceutical composition of claim 7 for treating patients suffering from multiple myeloma, or another BCMA-expressing B-cell malignancy. The BCMA-expressing B-cell malignancy is Waldenström's macroglobulinemia, Burkitt's lymphoma, diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, marginal cell lymphoma 14. The pharmaceutical composition of claim 13, selected from the group consisting of zonular lymphoma, lymphoplasmacytic lymphoma, and Hodgkin's lymphoma. 15. The pharmaceutical composition of any one of claims 11-14, for use in combination with a second therapeutic agent or therapeutic regimen; optionally wherein said second therapeutic agent or therapeutic regimen is , chemotherapeutic drugs, DNA alkylating agents, immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors, radiotherapy, stem cell transplantation, different doublets that interact with different tumor cell surface antigens and T-cell or immune cell antigens. said pharmaceutical composition comprising a specific antibody, an antibody drug conjugate, a bispecific antibody conjugated to an anti-tumor agent, a PD-1, PD-L1, or CTLA-4 checkpoint inhibitor, or combinations thereof thing. 8. The pharmaceutical composition according to claim 7, for treating a patient suffering from a BCMA-expressing tumor in combination with an anti-PD-1 antibody or antigen-binding fragment thereof. 17. The pharmaceutical composition of claim 16, wherein said anti-PD-1 antibody or antigen-binding fragment is an anti-PD-1 antibody; optionally, said anti-PD-1 antibody is cemiplimab (REGN2810).