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Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin.


ABSTRACT: We report the observation of liquid-liquid phase separation in a solution of human monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective interprotein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable protein condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC3189021 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin.

Wang Ying Y   Lomakin Aleksey A   Latypov Ramil F RF   Benedek George B GB  

Proceedings of the National Academy of Sciences of the United States of America 20110915 40


We report the observation of liquid-liquid phase separation in a solution of human monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude o  ...[more]

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