TRI- OR TETRASPECIFIC ANTIBODIES Russian patent published in 2015 - IPC C07K16/46 C07K16/22 C12P21/08 A61K39/395 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology. What is described is a method for producing trispecific or tetraspecific antibodies, wherein the trispecific or tetraspecific antibody contains: a) a light chain or heavy chain of a full-size antibody possessing an ability to bind specifically to a first antigen specifically; and b) a modified light chain and modified heavy chain of the full-size antibody possessing an ability to bind specifically to a second antigen specifically, wherein variable domains VL and VH are substituted by each other and/or wherein constant domains CL and CH1 are substituted by each other; and c) wherein one or more single-chain antibodies possessing an ability to bind specifically to one or two additional antigen specifically are fused by means of a connector peptide with C- or N-terminal of the light chains or heavy chains specified in the sub-clause a) and/or b); wherein the method involves the stages: i) transforming a host cell by expression vectors including nucleic acid molecules coding a light chain and heavy chain of a full-size antibody, which specifically binds the first antigen; and a modified light and heavy chain of the full-size antibody, wherein the variable domains VL and VH are substituted by each other, and/or the constant domains CL and CH1 are substituted by each other, and wherein one to four single-chain antibodies are fused by means of the connector peptide with C- or N-terminals of the light chains or heavy chains (a) and/or (b); ii) culturing the host cell in the environment enabling synthesis of the above antigen molecule; and iii) recovering the above antigen molecule from the above culture. What is also presented is the host cell for producing the above trispecific or tetraspecific antibody, containing the expression vectors comprising the nucleic acid molecules coding the above antibodies.

EFFECT: invention enables producing the high-yield trispecific or tetraspecific antibody by reducing incorrect coupling of the antibody chains.

13 cl, 11 dwg, 3 tbl, 3 ex