Ultra-sub-stoichiometric "Dynamic" Bioconjugation Reduces Viscosity by Disrupting Immunoglobulin Oligomerization.

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.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Gong Y,Soleymani Abyaneh H,Drossis N,Niederquell A,Kuentz M,Leroux JC,de Haan HW,Gauthier MA

doi

10.1021/acs.biomac.9b00867

subject

Has Abstract

pub_date

2019-09-09 00:00:00

pages

3557-3565

issue

9

eissn

1525-7797

issn

1526-4602

journal_volume

20

pub_type

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