三种解决治疗性抗体自聚集的方法.pdfVIP

REPORT mAbs 6:6, 1533--1539; November/December 2014; © 2014 Taylor Francis Group, LLC Resolving self-association of a therapeutic antibody by formulation optimization and molecular approaches 1 1 1 2 1 1 1 Paul Casaz , Elisabeth Boucher , Rachel Wollacott , Brian G Pierce , Rachel Rivera , Maja Sedic , Sadettin Ozturk , William D Thomas Jr1, and Yang Wang1,* 1MassBiologics of the University of Massachusetts Medical School; Boston, MA USA; 2Program in Bioinformatics and Integrative Biology; University of Massachusetts Medical School; Worcester, MA USA Keywords: monoclonal, antibody, gelation, framework, formulation Abbreviations: CDR, complementarity-determining regions; PDB, Protein Data Bank A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self- association, formation of a semi-solid gel or “gelation. Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel whe