Bispecific Antibody, Antibody-Drug Conjugate and its Application

Claims

An antibody or antigen-binding portion thereof comprising a HER3 antigen-binding domain, wherein the HER3 antigen-binding domain comprises a VH (heavy chain variable region) and a VL (light chain variable region), wherein the VH comprises: (1-i) CDRs contained in a heavy chain comprising an amino acid sequence according to SEQ ID No. 15; (1-ii) an HCDR1 comprising an amino acid sequence according to SEQ ID No. 30, an HCDR2 comprising an amino acid sequence according to SEQ ID No. 31, and an HCDR3 comprising an amino acid sequence according to SEQ ID No. 32; or, (1-iii) an amino acid sequence according to SEQ ID No. 4 or a variant thereof; and / or, the VL comprises: (1-iv) the CDRs contained in a light chain comprising an amino acid sequence according to SEQ ID No. 16; (1-v) an LCDR1 comprising an amino acid sequence according to SEQ ID No. 33,an LCDR2 comprising an amino acid sequence according to SEQ ID No. 34, and an LCDR3 comprising an amino acid sequence according to SEQ ID No. 35; or, (1-vi) an amino acid sequence according to SEQ ID No. 5 or a variant thereof; preferably, the CDRs are defined by the Kabat, Chothia, AbM or IMGT numbering system; Preferably, the variant is a sequence that has a sequence identity of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% compared to the sequence from which it is derived, or has a substitution, deletion, or addition of one or more amino acids (for example, a substitution, deletion, or addition of 1, 2, 3, 4, or 5 amino acids) compared to the same; preferably,The substitution is a conservative substitution. An isolated nucleic acid molecule, encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 18. A vector, comprising the nucleic acid molecule according to claim 19; preferably, the nucleic acid sequences encoding different peptide chains of the antibody or antigen-binding fragment thereof are arranged in the same or different vectors; preferably, the vector is a cloning vector or an expression vector. A host cell, comprising the nucleic acid molecule according to claim 19 or the vector according to claim 20. A pharmaceutical composition, comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 18, the nucleic acid molecule according to claim 19,the vector according to claim 20, the host cell according to claim 21 or the antibody-drug conjugate according to any of claims 23 to 28, and a pharmaceutically acceptable excipient; Preferably, the pharmaceutical composition has a drug-to-antibody ratio (DAR) of 1 to 8, such as 1 to 1.5, 1 to 2, 1 to 2.5, 1 to 3, 1 to 3.5, 1 to 4, 1 to 4.5, 1 to 5, 1 to 5.5, 1 to 6, 1 to 6.5, 1 to 7, 1 to 7.5, 1 to 8, 1.5 to 2, 1.5 to 2.5, 1.5 to 3, 1.5 to 3.5, 1.5 to 4, 1.5 to 4.5, 1.5 to 5, 1.5 to 5.5, 1.5 to 6, 1.5 to 6.5, 1.5 to 7, 1.5 to 7.5, 1.5 to 8, 2 to 2.5, 2 to 3, 2 to 3.5, 2 to 4, 2 to 4.5, 2 to 5, 2 to 5.5, 2 to 6, 2 to 6.5, 2 to 7, 2 to 7.5, 2 to 8, 2.5 to 3, 2.5 to 3.5, 2.5 to 4, 2.5 to 4.5, 2.5 to 5, 2.5 to 5.5, 2.5 to 6, 2.5 to 6.5, 2.5 to 7, 2.5 to 7.5, 2.5 to 8, 3 to 3.5, 3 to 4, 3 to 4.5, 3 to 5, 3 to 5.5, 3 to 6, 3 to 6.5, 3 to 7, 3 to 7.5, 3 to 8, 3.5 to 4, 3.5 to 4.5, 3.5 to 5, 3.5 to 5.5, 3.5 to 6, 3.5 to 6.5, 3.5 to 7, 3.5 to 7.5, 3.5 to 8, 4 to 4.5, 4 to 5, 4 to 5.5, 4 to 6,4 a 6,5, 4 a 7, 4 a 7,5, 4 a 8, 4,5 a 5, 4,5 a 5,5, 4,5 a 6, 4,5 a 6,5, 4,5 a 7, 4,5 a 7,5, 4,5 a 8, 5 a 5,5, 5 a 6, 5 a 6,5, 5 a 7, 5 a 7,5, 5 a 8, 5,5 a 6, 5,5 a 6,5, 5,5 a 7, 5,5 a 7,5, 5,5 a 8, 6 a 6,5, 6 a 7, 6 a 7,5, 6 a 8, 6,5 a 7, 6,5 a 7,5, 6,5 a 8, 7 a 7,5, 7 a 8, 7,5 a 8.,