Adsorption Behavior of Charge Isoforms of Monoclonal Antibodies on Strong Cation Exchangers

被引:4
|
作者
Steinebach, Fabian [1 ]
Waelchli, Ruben [1 ]
Pfister, David [2 ]
Morbidelli, Massimo [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Chem & Bioengn, CH-8093 Zurich, Switzerland
[2] Ypso Facto, 10 Viaduc Kennedy, F-54000 Nancy, France
关键词
antibodies; bioprocess development; chromatography; downstream processing; modeling; MODEL-BASED DESIGN; RECOMBINANT ANTIBODY; PROTEIN ADSORPTION; MASS-SPECTROMETRY; GRADIENT APPROACH; CELL-CULTURE; CHROMATOGRAPHY; VARIANTS; HETEROGENEITY; SEPARATION;
D O I
10.1002/biot.201700123
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
In this work, the adsorption behavior of the different charge isoforms of the same monoclonal antibody (mAb) on strong cation-exchange resins is analyzed. While charge isoforms of the same antibody mainly differ in their effective charge, the similar structure and size allows developing a simplified model, which describes the adsorption behavior of mAb charge isoforms independently of the number of isoforms with only four parameters. In contrast to classical model-based descriptions of the adsorption isotherm, the proposed work enables retrieving some physical meaning in the definition of the model parameters. These model parameters are determined for several resin-antibody combinations. Thereby it is found that for mAbs on commercial cation exchangers an effective resin charge density of 0.22 +/- 0.08mmolmL(-1) of solid phase is used for protein binding, which was found to be independent of the absolute resin charge density measured by titration. The presented results help to understand the adsorption behavior of mAbs on cation-exchangers, which is applicable both for the isolation of the main charge isoform or for preserving a certain charge isoform pattern during the polishing processes.
引用
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页数:9
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