Application Note


Utilising multi-parameter epitope binning to understand a therapeutic antibody’s mechanism of action


U


nderstanding an antibody’s mecha- nism of action (MOA) is critical to its clinical success. Not only does


MOA have a large impact on safety and efficacy, but it also influences the intellectu- al property (IP) and commercial potential of a therapeutic. Those antibodies with novel MOAs represent significant opportu- nities in the competitive world of pharma- ceuticals, and so identifying them is key. High throughput Surface Plasmon


Resonance (SPR) offers a unique advan- tage in the quest for successful next-gener- ation therapeutic antibodies. Its expanded capabilities compared with traditional SPR and other label-free methods enable comprehensive screening of antibody libraries at the earliest stage of drug dis- covery, with the additional advantage of high-resolution binding characterisation through kinetics and epitope binning assays. This technology facilitates a paradigm shift in antibody discovery, identifying blocking relationships for a whole antibody panel from the beginning for a streamlined and highly-informed lead selection process. The results from epitope binning provide


the first layer of information in construct- ing a detailed fingerprint of an antibody library, where groups of antibodies are clustered together based upon their epitope specificity, which correlates to their func- tional activity. In other words, antibodies targeting the same or similar epitope are likely to share the same or similar MOA. Combining orthogonal data from function- al and other studies builds on this layer-by- layer, helping researchers to navigate through the epitope landscape, prioritising resources and characterising binding inter- actions to aid in elucidating MOA. Understanding the significance of multi- parameter data within the context of an antibody library’s epitope landscape,


Drug Discovery World Winter 2019/20


enables an informed selection of high-value clones based on MOA, and subsequent pri- oritisation of resources to converge upon high-quality therapeutic candidates. Using the Carterra LSA platform for


high throughput SPR, it is possible to per- form multi-parameter epitope binning to understand a therapeutic antibody’s mech- anism of action – a critical feature in drug discovery and development campaigns.


Before High Throughput SPR


ELISA (binders) Quantitation Hit Specificity


Solution Competition Kinetics


Epitope Binning


Weak binders missed? Epitope diversity preserved?


3


Using High Throughput SPR


Kinetics Specificity Epitope


Quantitation Informed Decision


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