摘要 |
FIELD: biotechnology.SUBSTANCE: present invention relates to bioengineering and immunology. Method of obtaining a bispecific antigen-binding protein, comprising a modified heavy chain of a first antibody, which specifically binds to a first antigen, C-terminus of which is additionally fused with N-terminus of VH-CH1 domains of said first antibody via a peptide connector; two light chains of said first antibody; a modified heavy chain of a second antibody, which specifically binds to a second antigen, wherein CH1 domain is replaced by CL domain of second antibody and C-terminus is additionally fused with N-terminus of VH-CL of second antibody via a peptide connector; and two modified light chains of second antibody, wherein CL domain is replaced by CH1 domain of second antibody, CH3 domains of heavy chains contact each other on "knob-into-holes" principle. Also provided is a host cell for producing said bispecific antibody.EFFECT: present invention provides stable bispecific antibodies with high output and can further be used in development of therapeutic tetravalent antibodies.4 cl, 4 dwg |