Bispecific antibodies (bsAbs) are a promising class of therapeutic agents due to their ability to bind to two different types of antigens or two different epitopes on the same antigen. This ability allows bsAbs to be more effective at treating diseases. However, due to their increased complexity bsAbs often have higher levels of impurities in comparison to monoclonal antibodies (mAbs). This presents challenges to downstream processing.
This web article describes how Bioprocessing Technology Institute (BTI), Singapore together with scientists at Cytiva developed an optimized capture step for two closely related knob-into-hole (KiH) bsAbs using MabSelect PrismA™ protein A resin which reached a purity of 94%. In addition, two flow-through polishing steps using orthogonal binding principles, hydrophobic interaction and hydrophobic/anion exchange, further reduced the impurities to achieve a monomeric purity of 99%.