The Biology

Interface Exchange

A major challenge in the engineering of bispecific antibodies is to produce a heterodimeric bispecific antibody without the presence of contaminating homodimeric antibodies.

Glenmark’s scientists turned to nature to solve this engineering problem and designed a bio-mimicry strategy to establish a stable heterodimer. Hijacking the T-cell receptor (TCR) constant domain alpha/beta interface found on natural T-cells and grafting it onto the antibody CH3 homodimer interface results in two different heavy chains that readily assemble. This innovative solution results in an antibody highly similar to a natural one as only the buried interfaces of the CH3 homodimer domains are modified.