Ultra-sub-stoichiometric “Dynamic” Bioconjugation
Reduces Viscosity by Disrupting Immunoglobulin Oligomerization
Version 2 2019-08-23, 14:42
Version 1 2019-08-23, 14:33
Posted on 2019-08-23 - 14:42
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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Gong, Yuhui; Soleymani Abyaneh, Hoda; Drossis, Nicole; Niederquell, Andreas; Kuentz, Martin; Leroux, Jean-Christophe; et al. (2019). Ultra-sub-stoichiometric “Dynamic” Bioconjugation
Reduces Viscosity by Disrupting Immunoglobulin Oligomerization. ACS Publications. Collection. https://doi.org/10.1021/acs.biomac.9b00867
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AUTHORS (8)
YG
Yuhui Gong
HS
Hoda Soleymani Abyaneh
ND
Nicole Drossis
AN
Andreas Niederquell
MK
Martin Kuentz
JL
Jean-Christophe Leroux
Hd
Hendrick W. de Haan
MG
Marc A Gauthier