Dynamic cluster formation, viscosity, and diffusion in monoclonal antibody solutions depending on antibody type and crowding
Within an InnovaXN EU MSCA COFUND PhD project (www.innovaxn.eu) in collaboration with the pharmaceutical company Lonza AG (Basel, Switzerland), we wish to explore different kinds of medically important IgG1-type monoclonal antibodies (mAbs) in aqueous (D2O) solutions. The aim of this research is to unambiguously determine the size of possibly transient clusters via their short-time self-diffusion accessible by neutron backscattering spectroscopy, depending on the kind of mAb. Previous research by Lonza AG has established that the 5 different kinds of mAbs proposed as samples here drastically differ in their macroscopic viscosity, although the structural difference of these mAbs is minimal. Theoretical work establishes that the macroscopic viscosity, and the nanometer length scale diffusion properties and possible transient cluster formation are fundamentally linked by so-called Generalized Stokes-Einstein (GSE) relations. Here we aim to provide crucial data required to experimentally test the GSE and to ultimately be able to predict the macroscopic viscosity based on molecular properties and, hence, to improve mAb drug formulations for which viscosity is a limiting factor.
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COLIN Louise; BECK Christian; GIRELLI Anita; GRAPENTIN Christoph; MATSARSKAIA Olga; POUNOT Kevin; Frank Schreiber and SEYDEL Tilo. (2021). Dynamic cluster formation, viscosity, and diffusion in monoclonal antibody solutions depending on antibody type and crowding. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-04-908
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