Novel bifunctional antibody and application thereof

Abstract

The invention provides an antibody. The antibody comprises a protein dimer, wherein the protein dimer comprises a first functional domain including an immunoglobulin chain or an antibody combining site of a specifically-recognized specific antigen and a second functional domain including an immunoglobulin chain or an antibody combining site of a specifically-recognized specific antigen. The antibody is characterized in that the first functional domain consists of a first VH structural domain and a first VL structural domain, and the second functional domain consists of a second VH structural domain. The VH is a heavy chain variable zone, and the VL is a light chain variable zone. The bifunctional antibody provided by the invention has the advantages that a half-life period is greatly prolonged; and a homodimer is extremely less, so that identification and removal can be carried out only through primary purification even if aggregates occur.

Description

Technical field [0001] The present invention relates to a bifunctional antibody, in particular to a novel bifunctional antibody. Background technique [0002] Bispecific antibodies (BsAb), also known as bifunctional antibodies, can simultaneously recognize and bind to two different antigens and epitopes, and block two different signal pathways to play its role. According to different structures, there are two main types of bispecific antibody structures: bispecific antibodies containing Fc fragments (IgG-like bispecific antibodies) and bispecific antibodies without Fc fragments (non-IgG-like bispecific antibodies). Specific antibodies). [0003] An important mechanism of bispecific antibodies is to mediate the killing of immune cells. Bispecific antibodies have two antigen-binding arms, one of which binds to the target antigen, the other binds to the labeled antigen on the effector cell, the latter can activate the effect Cells to target and kill tumor cells. The two bispecific ...

AI Technical Summary

Problems solved by technology

[0004] However, the existing forms of bifunctional antibodies generally face problems such as easy aggregation, low purification yield, poor stability, or short blood half-life.

CN104829726A provides a bispecific CD19XCD3 antibody, but the antibody is easy to form homodimers, which is difficult to identify and remove, which greatly increases the difficulty of purification and identification, and limits its industrial application

At present, there are many forms of bifunctional antibodies, but they generally face problems such as easy aggregation, low purification yield, poor stability or short blood half-life.

For example, CN107556387A provides a chained anti-GPC3 / CD3 bispecific antibody, although it can specifically recognize and bind GPC3 antigen and GPC3 overexpressed tumor cells, and mediate the killing effect of T cells, but the structure is the same as that of the blinatumomab antibody BITE Structurally similar, has been shown to have a short blood half-life of only a few hours

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