(408b) Engineering and Characterizing Aggregation-Resistant Antibodies
AIChE Annual Meeting
2012
2012 AIChE Annual Meeting
Biomedical Applications of Chemical Engineering
Biophysical Behavior of Pharmaceutical Proteins in Processing, Storage and Delivery Environments II
Wednesday, October 31, 2012 - 9:10am to 9:30am
Protein aggregation is one of the most significant challenges in successfully developing and delivering monoclonal antibodies for therapeutic applications. We are investigating how to engineer the sequences of antibodies to promote high solubility without altering biological activity, as well as how to identify optimal formulation conditions that maximize antibody solubility using high-throughput measurements of antibody self-association. In this presentation, we will first discuss our work on investigating the impact of the complementarity determining regions (CDRs) of antibodies on their aggregation behavior for a library of homologous antibody fragments (Perchiacca et al., Proteins, 2011). Importantly, we find that charged mutations near the edges of hydrophobic CDR loops significantly increase antibody solubility without reducing binding activity. Second, we will discuss our development of a high-throughput method (self-interaction nanoparticle spectroscopy, SINS) for measuring antibody self-association (Sule et al., Biophys J, 2011). We find that SINS can reliably and rapidly identify sequence variants and formulation conditions that minimize monoclonal antibody aggregation.
See more of this Session: Biophysical Behavior of Pharmaceutical Proteins in Processing, Storage and Delivery Environments II
See more of this Group/Topical: Topical 7: Biomedical Applications of Chemical Engineering
See more of this Group/Topical: Topical 7: Biomedical Applications of Chemical Engineering