Optimizing asymmetric antibody purification: a semi-automated process and its digital integration

Over the past decades, immunization and display technologies have considerably increased the potential for generating new binders against cell surface targets. Concomitantly, the complexity of biologic therapeutic drugs has also increased, with new asymmetric formats such as bispecific antibodies or antibody fusion proteins making the supply of molecules for preclinical drug discovery more challenging. The purification of those molecules is crucial, and an efficient purification platform for drug discovery research units should have multiple aims. First, it needs to deliver the highest quality proteins for research activities at a fast pace in order to increase screening capacities. Second, it has to deliver protein with sufficient yield in order to cover the project requirements and minimize the repetition of production cycles. Through a case study for a bispecific antibody, we describe a semi-automated and digitalized purification platform aiming at accelerating and optimizing the supply of asymmetric antibodies for drug discovery. We show how the automation of repetitive tasks and the digitalization of the process can lead to increased throughput in the context of complex purifications, including a cation exchange chromatography separation step. Furthermore, we highlight how process digitalization leads to enhanced data capture and accessibility, facilitating decision-making along the purification process. With a maximal throughput of 36 asymmetric antibodies per week and data proving the consistency of the quality delivered, this platform represents a step forward in the supply of complex antibody formats for preclinical drug discovery.