Available Technologies

Background

　IgG-type bispecific antibodies (BsAbs), which have antibody variable domains that bind to two different epitopes of an antigen, are gaining attention as a new modality for the diagnostic and therapeutic pharmaceuticals development.
　BsAbs are expected for their enhanced binding ability, as they form large complexes through intermolecular cross-linking with two BsAb molecules binding to two epitopes. However, special manufacturing strategies are required to correctly pair the heavy and light chain variable regions for each of the two binding sites.
　To date, technologies such as knobs-into-holes and Duobody have been developed to form hetero-Fc dimers. However, four different light chain combinations can occur for each intended pairing of heavy chains, resulting in low yields and posing significant challenges in terms of separation and purification (Fig.1). For this, technological development that resolves this light chain issue is desired.

Description and Advantages

　The research team at Kyoto University has developed a new method to solve this light chain issue. Specifically, they identified a protein X as a molecule that is structurally similar to the CH1 and CL domains of IgG and does not interfere with pairing or cross-react with other parts. Furthermore, by applying appropriate modification processes to the protein X, they obtained the antigen-binding Fab-like molecule, with which BsAb can be produced in a single batch.