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In this work, we continue to examine excipient effects on the reversible self-association (RSA) of two different IgG1 monoclonal antibodies (mAb-J and mAb-C). We characterize the RSA behavior of mAb-C which, similar to mAb-J (see companion paper), undergoes concentration-dependent RSA, but by a different molecular mechanism. Five additives that affect protein hydrophobic interactions to varying extents including a chaotropic salt (guanidine hydrochloride, GdnHCl), a hydrophobic salt (trimethylphenylammonium iodide, TMPAI), an aromatic amino acid derivative (tryptophan amide hydrochloride, TrpNHHCl), a kosmotropic salt (sodium sulfate, NaSO), and a less polar solvent (ethanol) were evaluated to determine their effects on the solution properties, molecular properties, and RSA of mAb-C at various protein concentrations. Four of the five additives examined demonstrated favorable effects on the pharmaceutical properties of high concentration mAb-C solutions (i.e., lower viscosity and weakened protein-protein interactions, PPIs) with a ranking order of GdnHCl > TMPAI > TrpNHHCl > ethanol as measured by various biophysical techniques. Conversely, addition of NaSO resulted in less desirable solution properties and enhanced PPIs. The effect of these five additives on mAb-C backbone dynamics were evaluated by HX-MS (at high vs. low protein concentrations) to better understand their effects on the molecular sites of RSA in mAb-C.
This article was published in the following journal.
Name: Journal of pharmaceutical sciences
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