Anti-her2/cd3 bispecific antibody specifically activated in tumor microenvironment
AssigneeYing Mai De Medical Technology (Guangdong) Co., Ltd.
InventorsChengli DING, Yuan LIU, Chen LIU
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Abstract
An anti-Her2/CD3 bispecific antibody is specifically activated in a tumor microenvironment. The bispecific antibody can be chemically conjugated to a substrate that is highly expressed in a tumor environment and can be recognized and cut, as well as a masking moiety, in a chemical coupling manner. The antibody activity of the bispecific antibody in normal tissues is suppressed, but is activated in a tumor environment. In addition, the bispecific antibody also has a significantly reduced toxicity.
Claims20
A mutant CD3 antibody, wherein one or more mutations are introduced in the complementary determining regions (CDR regions) of the heavy chain variable region and/or light chain variable region of the mutant CD3 antibody relative to a wild-type CD3 antibody sequence, wherein the mutation is selected from the group consisting of:
- a mutation where one or more amino acids are replaced with cysteine (Cys) at the position of M34, S53, Y61, D68, F104, Will, or F112 in the heavy chain variable region;
- and/or at the position of N54, K55, R56, W93, Y94 or N96 in the light chain variable region;
- wherein, the affinity of the wild-type CD3 antibody for binding to CD3 is E0, the affinity of the mutant CD3 antibody for binding to CD3 is E1, and E1/E0≤5.5 (preferably E1/E0≤3, preferably ≤1.5, more preferably E1/E0≤1);
- wherein the heavy chain variable region of the wild-type CD3 antibody comprises the following three complementary determining regions (CDRs):
- VH-CDR1 as shown in SEQ ID NO.1,
- VH-CDR2 as shown in SEQ ID NO.2, and
- VH-CDR3 as shown in SEQ ID NO.3;
- and
- the light chain variable region of the wild-type CD3 antibody comprises the following three complementary determining regions (CDRs):
- VL-CDR1 as shown in SEQ ID NO.5,
- VL-CDR2 as shown in SEQ ID NO.6, and
- VL-CDR3 as shown in SEQ ID NO.7.
Dependencies are inferred from the claim text.