Scientific Poster: Development of High Throughput Screening Tools for Purification of Bispecifics

21st May 2024

Access our recent poster from PEGS 2024 in Boston on Bispecifics

Abstract

Antibodies have been used as therapeutics for over 30 years but can have a limited modality. In recent years advances in protein engineering have allowed us to build antibody structures with two (or more) specificities – bispecific antibodies.

Despite the varied molecular engineering strategies that have been developed to ensure correct bispecific assembly,there remains the potential for incorrect pairing i.e. formation of monospecific homodimers, which often require significant and time-consuming USP and DSP optimization. Here we demonstrate the development of high throughput screening for purification of different bispecific formats.

Three bispecific molecules against the same two targets, were expressed in different formats that incorporated different molecular engineering strategies. These were expressed in the AbZelect CHO platform at small scale and purified. For two constructs, purification using platform affinity capture and polishing steps were effective however, for one format, heterodimeric Fab/scFv-Fc, these standard approaches failed to give acceptable purity or yields. We demonstrate how high throughput resin screening was performed using the Cytiva PreDictor plates to rapidly develop a method for effective purification of this construct and discuss an approach for rapidly screening different bispecific formats to identify the optimal arrangement for any two specificities, taking developability and function into account.

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Abzena poster authors include: Beata Blaszczyk, Elizabeth Willows, Kalpana Wood, Prakash Nayee, Marina Leal, William McDowell, Nicole Wakes, Simon Keen, Rob Holgate*