PMID: 9188166Jan 1, 1997Paper

A case study and use of sedimentation equilibrium analytical ultracentrifugation as a tool for biopharmaceutical development

European Biophysics Journal : EBJ
P G VarleyN R Burns

Abstract

Analytical ultracentrifugation (AUC) has reemerged as a powerful technique for protein characterisation. We report the pivotal role sedimentation equilibrium AUC has played in the development of macrophage inflammatory protein-1 alpha (MIP-1 alpha) as a protein therapeutic. MIP-1 alpha has potential clinical applications in cancer but its clinical use is limited, since it associates to form large insoluble aggregates in physiological buffers. Using AUC as a screening technique, we have produced a biologically active variant of MIP-1 alpha, BB-10010, which has a reduced tendency to aggregate in physiological buffers. The aggregation of protein based pharmaceuticals is routinely monitored by size exclusion chromatography (SEC). Comparison of the data acquired by SEC and AUC, demonstrates that owing to the complexity of BB-10010, AUC analysis is required in addition to SEC to provide a rigorous characterisation of molecular association. This work has been extended to include the use of AUC as an analytical tool to monitor the quality of BB-10010 during formulation and stability studies.

Citations

Apr 21, 2005·European Biophysics Journal : EBJ·Corrine J PorterJackie A Wilce
Dec 26, 2001·Pharmaceutical Science & Technology Today·D A Parkins, U T Lashmar
Nov 6, 2004·Nature Biotechnology·Arthur J Chirino, Anthony Mire-Sluis
Dec 10, 1999·Journal of Pharmaceutical Sciences·J Liu, S J Shire
Oct 1, 2008·Journal of Pharmaceutical Sciences·Hanns-Christian MahlerSylvia Kiese
Aug 20, 2011·Biomedical Chromatography : BMC·Marcello LocatelliFrancesco Epifano
May 4, 2016·Journal of Molecular Biology·Damian delToroDouglas E Smith
Mar 13, 2002·The Journal of Biological Chemistry·E Sonay KuloğluBrian F Volkman
Jul 7, 2007·Critical Reviews in Toxicology·Yasuhiro Masubuchi, Toshiharu Horie

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