The emerging role of biosensor-based epitope binning and mapping in antibody-based drug discovery

ABSTRACT

Introduction: Surface plasmon resonance (SPR) for affinity/kinetics measurements of drug candidates has been a mainstay application for characterizing drug candidates for many years. Recently, with the growth of monoclonal antibodies (mAbs) as a drug class and the availability of higher-throughput biosensors, the role of label-free biosensors has evolved to include epitope characterization in the early drug discovery process through epitope binning and mapping of mAbs.

Areas covered: This manuscript outlines the importance of using epitope characterization early in the drug discovery process and describes a strategy for success in discovering drug leads. Updated practices for integrating epitope characterization with other biochemical/biophysical data, cell-based functional data, and computational prediction tools are also discussed.

Expert opinion: The authors propose using epitope characterization during early drug discovery by: (1) using epitope binning of mAbs following the pre-screening of clones to assure selection of mAb candidates with epitope diversity, (2) binning the maximum number of mAbs in order to fully define epitope engagement profiles, and (3) integrating epitope binning/mapping data with binding affinity, kinetics, cell-based functional assays, etc. to better describe functional epitope. This approach, together with structural and binding prediction data, will improve the quality of leads and improve the selection speed for clinical candidates.

KEYWORDS:

• Drug discovery
• epitope
• epitope binning
• epitope mapping
• SPR
• high-throughput screening

Article highlights

• Surface plasmon resonance (SPR) for affinity/kinetics measurements of drug candidates has been a mainstay application for characterizing drug candidates for many years.

• Screening therapeutic monoclonal antibodies by epitope has become the best screening criteria during the early mAb drug discovery process.

• Epitope characterization through binning improves intellectual property (IP) positions and increases R&D productivity, and guides engineering allowing for best in class therapeutic development.

• Epitope binning is not a stand-alone tool and requires additional supporting evidence for informed screening decisions including binding kinetics/affinity, cross-reactivity, cell-based functional assay, and other biophysical/structural data.

• Binning and mapping will also change how antidrug antibodies are detected and characterized.

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Declaration of interest

N Ditto and B Brooks are employed by Wasatch Microfluidics and have a financial interest in the company. Wasatch sells instruments that are used for epitope binning and epitope mapping. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript is funded by Wasatch Microfluidics.