Therapeutic antibody discovery

Abstract The last 30 years has seen a dramatic expansion in the development and production of therapeutic antibody products entering clinical trials and attaining approval from the US Food and Drug Administration. The therapeutic antibody discovery process takes 1–2 years from the choice of disease area and validation of a drug target, to the development and production of a lead antibody candidate for entrance into preclinical and clinical development. At the start of this process a target product profile (TPP) is created defining desired antibody characteristics to align with a hypothesized therapeutic mechanism of action (MOA). Antibodies are discovered for a therapeutic target through in vivo and in vitro antibody-generation campaigns. Utilizing high-throughput screening, individual antibodies displaying desired binding properties are identified and moved into a process known as hit-and-lead generation. Aligning with the TPP, antibodies are analyzed for biochemical, biophysical, and functional properties. Antibodies are optimized to add enhancements of function, improve physical and chemical stability, modify antigen binding affinities and selectivity, and finalize the formatting of the therapeutic lead molecule. Lead molecules are selected based upon functional and biophysical criteria established in the TPP, resulting in the filing of the molecule for Investigational New Drug (IND) status with the FDA.