FIELD: biochemistry.
SUBSTANCE: invention relates to biochemistry, in particular to a method for producing a bispecific antibody comprising the steps of obtaining the first and second half-antibody, providing the first and second half-antibodies at pH 5–9; mixing the first and second half-antibodies to form an assembly mixture into which excess glutathione is added, and incubating the assembly mixture to produce a bispecific antibody. Also disclosed is a method for preparing a bispecific antibody that comprises preparing the first and second half-antibodies at a pH of 5–9 in the presence of arginine or histidine, mixing the first and second half-antibodies to form an protein assembly mixture in a reducing condition and incubating the protein assembly mixture to form a bispecific antibody.
EFFECT: invention provides an improved assembly of heteromultimeric proteins, such as bispecific antibodies, with higher yield and efficacy.
33 cl, 7 dwg, 6 ex, 1 tbl
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