Ultra-sub-stoichiometric “Dynamic” Bioconjugation Reduces Viscosity by Disrupting Immunoglobulin Oligomerization

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Publication date
09.09.2019
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01A - Journal article
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Biomacromolecules
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Volume
20
Issue / Number
9
Pages / Duration
3557-3565
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American Chemical Society
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Abstract
Monoclonal antibodies (mAb) are a major focus of the pharmaceutical industry, and polyclonal immunoglobulin G (IgG) therapy is used to treat a wide variety of health conditions. As some individuals require mAb/IgG therapy their entire life, there is currently a great desire to formulate antibodies for bolus injection rather than infusion. However, to achieve the required doses, very concentrated antibody solutions may be required. Unfortunately, mAb/IgG self-assembly at high concentration can produce an unacceptably high viscosity for injection. To address this challenge, this study expands the concept of "dynamic covalent chemistry" to "dynamic bioconjugation" in order to reduce viscosity by interfering with antibody-antibody interactions. Ultra-sub-stoichiometric amounts of dynamic PEGylation agents (down to the nanomolar) significantly reduced the viscosity of concentrated antibody solutions by interfering with oligomerization.
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1525-7797
1526-4602
Language
English
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Yes
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Published
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Citation
GONG, Yuhui, Andreas NIEDERQUELL und Martin KUENTZ, 2019. Ultra-sub-stoichiometric “Dynamic” Bioconjugation Reduces Viscosity by Disrupting Immunoglobulin Oligomerization. Biomacromolecules. 9 September 2019. Bd. 20, Nr. 9, S. 3557–3565. DOI 10.1021/acs.biomac.9b00867. Verfügbar unter: https://irf.fhnw.ch/handle/11654/30639