Using High Throughput SPR to Assess the Binding Kinetics, Affinities, and Epitope Coverage of Antibody Libraries

Summary:

The generation of antibodies to source the discovery of therapeutics is highly commoditized and there is a trend towards producing fully human antibodies by in vitro and in vivo methods to reduce the risk of immunogenicity. The OmniChicken™ (Ligand Pharmaceuticals, Inc.) is a new transgenic animal platform that offers some unique advantages in the discovery of therapeutic antibodies. Upon immunization with human antigens, chickens produce antibodies that recognize a broader range of epitopes than those from mammalian hosts, due to the phylogenetic distance between humans and birds. Transgenic chickens expressing a human antibody repertoire harness the innate ability of wild-type chickens to yield a comprehensive immune response to human targets. Key observations underpinning the development of this exciting antibody platform were made possible through the use of detailed binding studies performed by high throughput surface plasmon resonance (SPR), using the Carterra® LSA®. The expanded epitope coverage includes antibodies that are cross-reactive to orthologs of the target, which are highly sought-after to enable preclinical toxicology and Mechanism of Action (MOA) studies in rodent and other species. Additionally, the antibody repertoire includes high-affinity antibodies. The potential for identifying antibodies that target novel epitopes with high affinity is of great benefit to drug discovery in the quest for the next blockbuster antibody therapeutic.