Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity.

Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity. Research Abstract Details 

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Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity. Abstract Text:

Reversible self-association of a monoclonal antibody (MAb) in a high concentration formulation results in a solution with a high viscosity. The nature of the self-association of full-length as well as antibody fragments has been studied by rheometry. Chaotropic anions reduced solution viscosity more than kosmotropic anions, a result that can be explained by the Hofmeister series and the net charge of the MAb. The effect of strong chaotropes, such as urea and guanidine HCl at concentration below 300 mM on solution viscosity was also investigated. While the secondary and tertiary structure of the MAb was not altered, as determined by circular dichroism measurements, guanidine HCl reduced viscosity much more effectively than urea. Since urea is uncharged and guanidine HCl is monovalent, this study indicated that a charge effect may be a more important factor than the chaotropic nature of excipients in reducing solution viscosity by breaking network self-association of a MAb. To further understand which part of a MAb participates in this network self-association, a series of titration studies using the full-length MAb, F(ab')(2), and Fab fragments was conducted. From this study, the Fab was found to be the primary site of the network self-association. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4219-4227, 2008.

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Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of pharmaceutical sciences

VOLUME: 97

Page Numbers: 4219-27

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ISSN: 1520-6017

DAY: 3

MONTH: Oct

YEAR: 2008

Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity. Information

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LANGUAGE: eng

NlmUniqueID: 2985195

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Grant and Affiliation Information for Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity.

AFFILIATION: Late Stage Pharmaceutical and Device Development, Genentech Inc., 1 DNA Way, South San Francisco, California 94080.

Country: United States

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MEDLINETA: J Pharm Sci

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