BISPECIFIC ANTIGEN-BINDING PROTEINS

FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to biotechnology and represents a method for producing a bispecific antigen-binding protein containing: two light chains and two heavy chains of a full-length antibody containing two Fab fragments and specifically binding to the first antigen; and two supplementary Fab fragments of the antibody, which specifically binds to the second antigen, wherein the above both supplementary Fab fragments are fused by means of a connector peptide to C- or N-terminals of the heavy chains specified in sub-clause a); wherein the connector peptide represents (Gly-x-Ser)n, or (Gly-x-Ser)nGlym(x = 3, n = 3, 4, 5 or 6 and m = 0, 1, 2 or 3), or (x = 4, n = 2, 3, or 5 and m = 0, 1, 2 or 3) and wherein the Fab fragments are modified as follows: I) in both of the Fab fragments specified in sub-clause a), or in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and/or constant domains CL and CH1 are substituted by each other; II) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other; III) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other, or constant domains CL and CH1 are substituted by each other, and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other, and constant domains CL and CH1 are substituted by each other; IV) in both of the Fab fragments specified in sub-clause a), variable domains VL and VH are substituted by each other and in both of the Fab fragments specified in sub-clause b), constant domains CL and CH1 are substituted by each other; or V) in both of the Fab fragments specified in sub-clause a), constant domains CL and CH1 are substituted by each other and in both of the Fab fragments specified in sub-clause b), variable domains VL and VH are substituted by each other; whereas the method involves the stages of: a) transforming a host cell by means of expression vectors, which contain nucleic acid molecules coding the above bispecific antigen-binding protein; b) culturing the host cell in the environment, which enable synthes