To provide methods for efficiently producing antibodies and other multimeric
protein complexes capable of specifically binding to plural targets.SOLUTION: Disclosed is a method for preparing a heteromultimeric
protein that comprises a first hinge-containing polypeptide comprising a first heterodimerization domain bound to a
first light chain, and a second hinge-containing polypeptide comprising a second heterodimerization domain bound to a second light chain, where the second heterodimerization domain interacts with the first heterodimerized domain, the first and second hinge-containing polypeptides are linked via an interchain
disulfide bond, where the method comprises the steps of: culturing a first host
cell expressing the first hinge-containing polypeptide and the
first light chain; culturing a second host
cell expressing the second hinge-containing polypeptide and the second
heavy chain; and obtaining a
mixed culture medium of the first and second host cells without disrupting the
cell membranes of the first and second host cells.SELECTED DRAWING: Figure 1B