279447 Engineering and Characterizing Aggregation-Resistant Antibodies

Wednesday, October 31, 2012: 9:10 AM
Pennsylvania West (Westin )
Joseph M. Perchiacca1, Shantanu V. Sule2, Ali Reza A. Ladiwala2, Jayapriya Jayaraman2, Moumita Bhattacharya2 and Peter M. Tessier1, (1)Chemical & Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, (2)Dept of Chemical & Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY

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.

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