The invention relates to a method of preparing heteromultimeric
polypeptides such as bispecific antibodies, bispecific immunoadhesins and
antibody-immunoadhesin chimeras. The invention also relates to the
heteromultimers prepared using the method. Generally, the method provides
a multispecific antibody having a common light chain associated with each
heteromeric polypeptide having an antibody binding domain. Additionally
the method futher involves introducing into the multispecific antibody a
specific and complementary interaction at the interface of a first
polypeptide and the interface of a second polypeptide, so as to promote
heteromultimer formation and hinder homomultimer formation; and/or a free
thiol-containing residue at the interface of a first polypeptide and a
corresponding free thiol-containing residue in the interface of a second
polypeptide, such that a non-naturally occurring disulfide bond is formed
between the first and second polypeptide. The method allows for the
enhanced formation of the desired heteromultimer relative to undesired
heteromultimers and homomultimers.