Cation-exchange chromatography of monoclonal antibodies: Characterisation of a novel stationary phase designed for production-scale purification

Urmann, Marina; Graalfs, Heiner; Joehnck, Matthias; Jacob, Lothar R.; Frech, Christian

doi:10.4161/mabs.12303

Cited by 53 publications

(34 citation statements)

References 26 publications

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“…An early class of polymer-functionalized media was the Fractogel ™ EMD “tentacle” media [25], in which acrylamide derivatives were polymerized onto polymer base matrices, while the more recent media of this type include the Eshmuno ™ product line [29]. The monomers included groups functionalized to produce different ion-exchange ligands, including strong and weak cation and anion exchangers.…”

Section: Adsorbent Structurementioning

confidence: 99%

Protein adsorption and transport in polymer-functionalized ion-exchangers

Lenhoff

2011

Journal of Chromatography A

114

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A wide variety of stationary phases is available for use in preparative chromatography of proteins, covering different base matrices, pore structures and modes of chromatography. There has recently been significant growth in the number of such materials in which the base matrix is derivatized to add a covalently attached or grafted polymer layer or, in some cases, a hydrogel that fills the pore space. This review summarizes the main structural and functional features of ion exchangers of this kind, which represent the largest class of such materials. Although the adsorption and transport properties may generally be used operationally and modeled phenomenologically using the same methods as are used for proteins in conventional media, there are noteworthy mechanistic differences in protein behavior in these adsorbents. A fundamental difference in protein retention is that it may be portrayed as partitioning into a three-dimensional polymer phase rather than adsorption at an extended two-dimensional surface, as applies in more conventional media. Beyond this partitioning behavior, however, the polymer-functionalized media often display rapid intraparticle transport that, while qualitatively comparable to that in conventional media, is sufficiently rapid quantitatively under certain conditions that it can lead to clear benefits in key measures of performance such as the dynamic binding capacity. Although possible mechanistic bases for the retention and transport properties are discussed, appreciable areas of uncertainty make detailed mechanistic modeling very challenging, and more detailed experimental characterization is likely to be more productive.

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Section: Adsorbent Structurementioning

confidence: 99%

Protein adsorption and transport in polymer-functionalized ion-exchangers

Lenhoff

2011

Journal of Chromatography A

114

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“…Interestingly, use of Toyopearl GigaCap S-650 M, interestingly, has been shown to a suitable as a capture step for monoclonal antibodies with ≥90 g/L dynamic binding capacity operating at high linear flow rates up to 900 cm/h. Therefore this resin is readily scalable with significant cost savings in comparison to the traditionally used protein A resins [32,33]. …”

Section: Discussionmentioning

confidence: 99%

A Simplified and Efficient Process for Insulin Production in Pichia pastoris

Polez

Origi²,

Zahariev

et al. 2016

PLoS ONE

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A significant barrier to insulin is affordability. In this manuscript we describe improvements to key steps in the insulin production process in Pichia pastoris that reduce cost and time. The strategy for recovery and processing of human insulin precursor has been streamlined to two steps from bioreactor to the transpeptidation reaction. In the first step the insulin precursor secreted during the methanol induction phase is recovered directly from the culture broth using Tangential Flow Filtration with a Prostak™ module eliminating the laborious and time-consuming multi-step clarification, including centrifugation. In the second step the protein is applied at very high loadings on a cation exchange resin and eluted in a mixture of water and ethanol to obtain a concentrated insulin precursor, suitable for use directly in the transpeptidation reaction. Overall the yield from insulin precursor to human insulin was 51% and consisted of three purification chromatography steps. In addition we describe a method for recovery of the excess of H-Thr(tBu)-OtBu from the transpeptidation reaction mixture, one of the more costly reagents in the process, along with its successful reuse.

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“…However, the ion exchange resin process is limited in part by pressure drop across the resin bed during flow, which can be exacerbated by media deformation and non-uniform packing [6,7]. In several studies undertaken to correlate the pressure drop across packed beds of ion-exchange resin with flow rate, it was determined that the pressure drop must be known to design an ion exchange process effectively [8,9,10]. It was further determined that backwashing was required to minimize the pressure drop caused by resin fines and suspended solids [10].…”

Section: Introductionmentioning

confidence: 99%

Nanofiber Ion-Exchange Membranes for the Rapid Uptake and Recovery of Heavy Metals from Water

Chitpong

Husson

2016

Membranes

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An evaluation of the performance of polyelectrolyte-modified nanofiber membranes was undertaken to determine their efficacy in the rapid uptake and recovery of heavy metals from impaired waters. The membranes were prepared by grafting poly(acrylic acid) (PAA) and poly(itaconic acid) (PIA) to cellulose nanofiber mats. Performance measurements quantified the dynamic ion-exchange capacity for cadmium (Cd), productivity, and recovery of Cd(II) from the membranes by regeneration. The dynamic binding capacities of Cd(II) on both types of nanofiber membrane were independent of the linear flow velocity, with a residence time of as low as 2 s. Analysis of breakthrough curves indicated that the mass flow rate increased rapidly at constant applied pressure after membranes approached equilibrium load capacity for Cd(II), apparently due to a collapse of the polymer chains on the membrane surface, leading to an increased porosity. This mechanism is supported by hydrodynamic radius (Rh) measurements for PAA and PIA obtained from dynamic light scattering, which show that Rh values decrease upon Cd(II) binding. Volumetric productivity was high for the nanofiber membranes, and reached 0.55 mg Cd/g/min. The use of ethylenediaminetetraacetic acid as regeneration reagent was effective in fully recovering Cd(II) from the membranes. Ion-exchange capacities were constant over five cycles of binding-regeneration.

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Cation-exchange chromatography of monoclonal antibodies: Characterisation of a novel stationary phase designed for production-scale purification

Cited by 53 publications

References 26 publications

Protein adsorption and transport in polymer-functionalized ion-exchangers

Protein adsorption and transport in polymer-functionalized ion-exchangers

A Simplified and Efficient Process for Insulin Production in Pichia pastoris

Nanofiber Ion-Exchange Membranes for the Rapid Uptake and Recovery of Heavy Metals from Water

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