Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin
Autor: | Aleksey Lomakin, Ying Wang, George B. Benedek, Ramil F. Latypov |
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Rok vydání: | 2011 |
Předmět: |
Multidisciplinary
Chromatography biology medicine.drug_class Chemistry Condensation Temperature Albumin Antibodies Monoclonal Biological Sciences Human serum albumin Monoclonal antibody Blood proteins Biopharmaceutics Cryoglobulinemia Phase (matter) biology.protein medicine Humans Thermodynamics Antibody Serum Albumin Phase diagram medicine.drug |
Zdroj: | Proceedings of the National Academy of Sciences. 108:16606-16611 |
ISSN: | 1091-6490 0027-8424 |
DOI: | 10.1073/pnas.1112241108 |
Popis: | 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. |
Databáze: | OpenAIRE |
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