Format of bispecific antibodies (BsAbs)-Hetero H, CrossMab

CrossMab technology enforces correct light chain association based on the domain crossover of immunoglobulin domains in the Fab region of the bispecific antibody. CrossMab technology allow the generation of various bispecific antibody formats, including bi- (1+1), tri- (2+1) and tetra-(2+2) valent bispecific antibodies, as well as non-Fc tandem antigen-binding fragment (Fab)-based antibodies. These formats may be derived from any existing antibody pair using domain crossover, without the need for the identification of common light chains, post-translational processing/in vitro chemical assembly or the introduction of a set of mutations enforcing correct light chain association. The basis of the CrossMab technology is the crossover of antibody domains within one arm of a bispecific IgG antibody enabling correct chain association, whereas correct heterodimerization of the heavy chains can be achieved by the knob-into-hole technology or charge interactions. This can be achieved by exchange of either the Fab domains (in the CrossMabFab format), or only the variable VH-VL domains (CrossMabVH-VL format) or the constant CH1-CL domains (CrossMabCH1-CL format) within the Fab-fragment (Fig. 1). This class of therapeutics antibodies have novel mechanisms of actions as compared to conventional therapeutic antibodies and have a major impact on the treatment of various diseases, including oncology, infectious diseases, autoimmunity, CNS, and metabolic diseases. Taken together, CrossMab technology has proven to be very useful for the fast and straightforward generation of bispecific antibody formats to tackle novel biological challenges and help to develop novel therapeutic concepts.