Objective

In order to block multiple, different pathological factors and pathways to result in improved therapeutic efficacy, we have generated therapeutic bispecific antibodies as mAb-dAb (domain antibody) molecules. The dAb molecules with a second specificity are fused to the C-terminus of the heavy chain of a therapeutic mAb, with good productivity and stability. Generally, this format will maintain both productivity and antigen-binding activities for both targets, although issues regarding biophysical properties related stability have recently been addressed. Since the biophysical properties of the dAb partner can significantly contribute to the biophysical properties of a mAb-dAb, we have performed biophysical maturation alongside affinity maturation of the dAb by phage display. When compared to the mAb partner, we successfully obtained bi-specific mAb-dAbs with increased dAb affinity and improved biophysical characteristics compatible with our down stream drug development processes.