Strategies for Scalable and Sensitive Determination of High Affinity and Slow Dissociating Binding Interaction Kinetics in Antibody Discovery

Abstract

Monoclonal antibodies are powerful tools for therapeutic and diagnostic applications and binding kinetics is an important element of the potency and efficacy of these molecules. Many antibodies and optimized therapeutics show very high affinities with stable dissociation kinetics, and these high affinity interactions represent a challenge for accurate measurement using real time SPR binding studies, as slow dissociation yields minimal signal change over typical time courses. This poster explores two effective strategies using HT-SPR to measure slow dissociation of many interactions in parallel and with high sensitivity. The most sensitive and simple approach is the use of a chase injection to measure surface occupancy after a long dissociation period. The other is the use of both short and long dissociation times, which can enable an extended dissociation phase without excessively extending the overall length of an experiment. Both these approaches can be implemented at scale for the screening and characterization of hundreds to thousands of high affinity interactions using Carterra HT-SPR platforms.

Posted by Daniel Bedinger, PhD