Bispecific antibody heterodimers

摘要

Methods for producing and using bispecific antibodies formed by leucine zippers are provided. Leucine zippers capable of preferentially forming heterodimers are respectively linked to epitope binding components comprising different binding specificities. Bispecific antibodies are formed by pairwise association of the leucine zippers, forming a heterodimer which links the two distinct epitope binding components. Heterodimerization can occur by interaction of the two leucine zipper regions, forming a bispecific antibody. Such a bispecific antibody may be further stabilized by the formation of intermolecular chemical bonds, such as disulfide bonds, between the two monomeric subunits. Subsequent to the formation of such intermolecular bonds between the monomeric subunits, the leucine zippers may be removed or retained. Bispecific antibodies produced by these methods are substantially pure and may be produced in high yields and on a large scale. Alternatively, bifunctional heterodimers may be formed by linking an epitope binding component to a macromolecular species that is not an epitope binding component.