| abstract |
FIELD: immunology. n SUBSTANCE: method for preparing a bispecific antigen-binding molecule comprising the Fc domain and Fab fragments specifically binding to the first and second antigens, wherein the bispecific antigen-binding molecule provides a monovalent binding to the first and/or second antigens. One of the Fabs in this molecule is fused to the C-terminus of its heavy chain with the N-terminus of the heavy chain of another Fab fragment, which in turn is fused at the C-terminus of its heavy chain with the N-terminus of the Fc domain subunit. In at least one of the Fabs, one of the following substitutions is made: (i) variable domains of light chain (VL) and heavy chain (VH) are replaced by each other, or (ii) light chain constant domain (CL) and the first heavy chain constant domain (CH) CH1 are replaced with each other, provided that the first and second Fab fragments do not produce the same substitution. In addition, the Fc domain in the said molecule includes a modification stimulating the association of the Fc domain subunits. n EFFECT: present invention allows to obtain bispecific antigen-binding molecules with improved activity and can find application in preparation of therapeutic structures based on antibodies. n 25 cl, 27 dwg, 2 tbl, 5 ex |