Structure and Sequence Determinants of Nonspecificity and Aggregation of Therapeutic Antibodies
While high throughput methods such as phage and yeast display are frequently able to isolate high affinity antibodies against clinical targets, many of these antibodies fail in clinical stages due to poor pharmacokinetics and pharmacodynamics. Correcting these problems is an inexact science, costing significant time and money and often leading to promising drugs being abandoned altogether. It is my goal to first develop a high throughput assay to detect poor developability at an early stage, and then use this assay to determine the sequence and structure determinants of aggregation and nonspecificity. If successful, this should lead to better antibody library design and help ensure that antibodies isolated from display technologies will have favorable biophysical characteristics and be suitable for clinical applications.