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

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 pre...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-10, Vol.108 (40), p.16606-16611
Main Authors: Wang, Ying, Lomakin, Aleksey, Latypov, Ramil F, Benedek, George B
Format: Article
Language:English
Subjects:
additives
Antibodies
Antibodies, Monoclonal - metabolism
Biological Sciences
Biopharmaceutics
Blood
Condensation
Critical points
Cryoglobulinemia - metabolism
Drug interactions
Health savings accounts
human serum albumin
Humans
Material concentration
Molecules
Monoclonal antibodies
Phase diagrams
Physical Sciences
Proteins
Serum Albumin - metabolism
Serum Albumin - pharmacology
Temperature
Thermodynamics
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Summary: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 proetin condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1112241108