A method for making multispecific antibodies having heteromultimeric and common components

Abstract

A method for manipulating whole antibodies to create preferentially-associating heterodimers is described. This technique relies on the simple idea of introducing bulky residues at the C_H3 dimer interface, disrupting homodimer assembly. Cavities created in opposing positions in another C_H3 domain, permits the assembly of a ‘knob-into-hole’ heterodimer, resulting in a heterodimer yield of over 95%, compared to a possible mixture of ten products by conventional approaches. Heterodimers such as these result in bispecific antibodies (BsAbs) that have wide utility in target-effector cell targeting and tumour cell-specific delivery of therapeutic agents.

• assembly
• bispecific antibody
• heterodimers
• knob-into-hole
• recombinant expression