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Evaluation of Large Panels of Bispecific Antibodies Using Surface Plasmon Resonance

PEGS, Boston, MA, USA
May 3, 2017

Bispecific antibodies (BsAbs) have traditionally been developed by first optimizing antibody fragments then reformatting to the final bispecific format at the engineering stage. However, studies have shown that this method misses effective BsAbs. Moreover, costly engineering efforts are wasted optimizing BsAbs that once assembled turn out to be non-functional, unstable, or kinetically unsuitable. This is leading to a paradigm shift in BsAbs development: screening in the final therapeutic format as early as possible (“in-format screening”). This approach requires combinatorial cloning techniques to create large panels of BsAbs and subsequent high-throughput clone characterization. High-throughput Surface Plasmon Resonance (SPR) provides affinity as well as binding kinetics of clones against multiple antigens in one experiment. However, scaling up the approach presents a logistic and analytical challenge: how to effectively handle the large numbers of unique clones and efficiently analyze the SPR data. Here, we present a software solution to track the clones in the lab, automatically calculate kinetic parameters starting from raw SPR data, and use the calculated data and the sensorgrams to select the best hits for optimization. This workflow scales with the combinatorial complexity of the approach, ultimately reducing development times and providing better lead candidates for BsAbs.

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