Antigen-binding molecule
AssigneesJiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai Hengrui Pharmaceutical Co., Ltd.
InventorsHua Ying, Qiyue Hu, Xinsheng Jin, Jinping Shi, Ling Zhang, Langyong Mao, Xin Ye, Weikang Tao
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Abstract
Provided is an antigen-binding molecule, particularly a domain-engineered antibody, wherein at least one constant region domain CH1/CL of the antibody is replaced by a Titin T-chain/Obscurin-O chain.
Claims23
A dimerized polypeptide comprising a Titin-T chain and an Obscurin-O chain, or a Titin-T chain and an Obscurin-like-O chain, wherein,
- i) the Titin-T chain is a variant of SEQ ID NO:
- 32, wherein the variant has amino acid residue substitutions at one or more positions selected from the group consisting of positions 60 and 64 as compared to SEQ ID NO:
- 32, and/or
- ii) the Obscurin-O chain is a variant of SEQ ID NO:
- 33, wherein the variant has amino acid residue substitutions at one or more positions selected from the group consisting of positions 13, 32, 48, 66, 82, and 93 as compared to SEQ ID NO:
- 33;
- with the proviso that:
- a) when the variant does not have an amino acid residue substitution at position 13, 48, 66, 82, or 93, and has an amino acid residue substitution at position 32, the amino acid substitution at position 32 is not 32P;
- b) when the variant does not have an amino acid residue substitution at position 32, 48, 66, 82, or 93, and has an amino acid residue substitution at position 13, the amino acid substitution at position 13 is not 13Y;
- and
- c) when the variant does not have an amino acid residue substitution at position 48, 66, 82, or 93, and has amino acid residue substitutions at positions 13 and 32, the amino acid residue substitution at position 13 is not 13Y, and the amino acid residue substitution at position 32 is not 32P.
An antigen-binding molecule comprising a first antigen-binding moiety capable of specifically binding to PDL1 and a second antigen-binding moiety capable of specifically binding to TIGIT, wherein the first antigen-binding moiety comprises a heavy chain variable region VH1 and a light chain variable region VL1, and the second antigen-binding moiety comprises a heavy chain variable region VH2 and a light chain variable region VL2;
- wherein,
- the VH1 comprises HCDR1, HCDR2, and HCDR3 set forth in SEQ ID NOs:
- 163, SEQ ID NO:
- 164, and SEQ ID NO:
- 165, respectively, and the VL1 comprises LCDR1, LCDR2, and LCDR3 set forth in SEQ ID NO:
- 166, SEQ ID NO:
- 167, and SEQ ID NO:
- 168, respectively;
- and/or
- the VH2 comprises HCDR1, HCDR2, and HCDR3 set forth in SEQ ID NO:
- 157, SEQ ID NO:
- 158, and SEQ ID NO:
- 159, respectively, and the VL2 comprises LCDR1, LCDR2, and LCDR3 set forth in SEQ ID NO:
- 160, SEQ ID NO:
- 161, and SEQ ID NO:
- 162, respectively;
- preferably,
- the VH1 has a sequence set forth in SEQ ID NO:
- 156 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 156, and the VL1 has a sequence set forth in SEQ ID NO:
- 155 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 155;
- and/or
- the VH2 has a sequence set forth in SEQ ID NO:
- 154 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 154, and the VL2 has a sequence set forth in SEQ ID NO:
- 153 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 153;
- more preferably, the antigen-binding molecule has:
- a heavy chain having a sequence set forth in SEQ ID NO:
- 148 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 148;
- a first light chain having a sequence set forth in SEQ ID NO:
- 146 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 146;
- and
- a second light chain having a sequence set forth in SEQ ID NO:
- 147 or a sequence having at least 90% sequence identity to SEQ ID NO:
- 147.
Dependencies are inferred from the claim text.