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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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2012
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| Online Access: | http://hdl.handle.net/1721.1/72107 https://orcid.org/0000-0003-2414-524X https://orcid.org/0000-0001-6684-7608 |
| _version_ | 1826190230236954624 |
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| author | Wang, Ying Lomakin, Aleksey Latypov, Ramil F. Benedek, George B. |
| author2 | MIT Materials Research Laboratory |
| author_facet | MIT Materials Research Laboratory Wang, Ying Lomakin, Aleksey Latypov, Ramil F. Benedek, George B. |
| author_sort | Wang, Ying |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:37:04Z |
| format | Article |
| id | mit-1721.1/72107 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:37:04Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/721072022-09-23T13:19:16Z Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin Wang, Ying Lomakin, Aleksey Latypov, Ramil F. Benedek, George B. MIT Materials Research Laboratory Massachusetts Institute of Technology. Department of Physics Benedek, George B. Wang, Ying Lomakin, Aleksey Benedek, George B. 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. 2012-08-14T13:01:00Z 2012-08-14T13:01:00Z 2011-10 2011-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/72107 Wang, Y. et al. “Phase Separation in Solutions of Monoclonal Antibodies and the Effect of Human Serum Albumin.” Proceedings of the National Academy of Sciences 108.40 (2011): 16606–16611. Copyright ©2011 by the National Academy of Sciences https://orcid.org/0000-0003-2414-524X https://orcid.org/0000-0001-6684-7608 en_US http://dx.doi.org/10.1073/pnas.1112241108 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Wang, Ying Lomakin, Aleksey Latypov, Ramil F. Benedek, George B. Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| title | Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| title_full | Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| title_fullStr | Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| title_full_unstemmed | Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| title_short | Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| title_sort | phase separation in solutions of monoclonal antibodies and the effect of human serum albumin |
| url | http://hdl.handle.net/1721.1/72107 https://orcid.org/0000-0003-2414-524X https://orcid.org/0000-0001-6684-7608 |
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