Engineering of Monovalent, Multivalent and Bispecific Antibodies for New Therapeutic Applications

Engineered bispecific and tetravalent IgG-like antibodies that engage multiple target epitopes represent promising new classes of therapeutic agents. To address their intrinsic low stability and high aggregation propensity, we applied rational design to increase the thermostability of single chain Fv fragments without compromising their affinity towards antigen. Incorporation of these stabilized modules into full-length therapeutic bispecific and tetravalent molecules led to molecules with markedly improved properties. We additionally describe the development and characterization of new monovalent and heteromeric antibody platforms that allow us to interrogate the classes of targets, such as receptor tyrosine kinases and cytokines, which may be difficult to inhibit by bivalent antibodies.