Template-Assisted Crystallization Behavior in Stirred Solutions of the Monoclonal Antibody Anti-CD20: Probability Distributions of Induction Times.

Autor: Gerard CJJ; EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, Strathclyde Institute of Pharmacy and Biomedical Sciences, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, U.K.; SMS Laboratory EA 3233, Place Emile Blondel, University of Rouen-Normandie, CEDEX, F-76821 Mont Saint Aignan, France., Briuglia ML; EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, Strathclyde Institute of Pharmacy and Biomedical Sciences, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, U.K., Rajoub N; EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, Strathclyde Institute of Pharmacy and Biomedical Sciences, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, U.K., Mastropietro TF; Consiglio Nazionale delle Ricerche (CNR), Istituto per la Tecnologia delle Membrane (ITM), Via P. Bucci, cubo 17/C, I-87036, Rende, Cosenza, Italy., Chen W; Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, U.K., Heng JYY; Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, U.K., Di Profio G; Consiglio Nazionale delle Ricerche (CNR), Istituto per la Tecnologia delle Membrane (ITM), Via P. Bucci, cubo 17/C, I-87036, Rende, Cosenza, Italy., Ter Horst JH; EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, Strathclyde Institute of Pharmacy and Biomedical Sciences, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, U.K.; SMS Laboratory EA 3233, Place Emile Blondel, University of Rouen-Normandie, CEDEX, F-76821 Mont Saint Aignan, France.
Jazyk: angličtina
Zdroj: Crystal growth & design [Cryst Growth Des] 2022 Jun 01; Vol. 22 (6), pp. 3637-3645. Date of Electronic Publication: 2022 May 05.
DOI: 10.1021/acs.cgd.1c01324
Abstrakt: We present a method to determine the template crystallization behavior of proteins. This method is a statistical approach that accounts for the stochastic nature of nucleation. It makes use of batch-wise experiments under stirring conditions in volumes smaller than 0.3 mL to save material while mimicking larger-scale processes. To validate our method, it was applied to the crystallization of a monoclonal antibody of pharmaceutical interest, Anti-CD20. First, we determined the Anti-CD20 phase diagram in a PEG-400/Na 2 SO 4 /water system using the batch method, as, to date, no such data on Anti-CD20 solubility have been reported. Then, the probability distribution of induction times was determined experimentally, in the presence of various mesoporous silica template particles, and crystallization of Anti-CD20 in the absence of templates was compared to template-assisted crystallization. The probability distribution of induction times is shown to be a suitable method to determine the effect of template particles on protein crystallization. The induction time distribution allows for the determination of two key parameters of nucleation, the nucleation rate and the growth time. This study shows that the use of silica particles leads to faster crystallization and a higher nucleation rate. The template particle characteristics are shown to be critical parameters to efficiently promote protein crystallization.
Competing Interests: The authors declare no competing financial interest.
(© 2022 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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