Abstract
There is strong need to reduce the manufacturing costs and increase the downstream purification efficiency of high-value therapeutic monoclonal antibodies (mAbs). This paper explores the performance of a weak cation-exchange membrane based on the coupling of IDA to poly(butylene terephthalate) (PBT) nonwoven fabrics. Uniform and conformal layers of poly(glycidyl methacrylate) (GMA) were first grafted to the surface of the nonwovens. Then IDA was coupled to the polyGMA layers under optimized conditions, resulting in membranes with very high permeability and binding capacity. This resulted in IgG dynamic binding capacities at very short residence times (0.1–2.0 min) that are much higher than those achieved by the best cation-exchange resins. Similar results were obtained in the purification of a single-chain (scFv) antibody fragment. As is customary with membrane systems, the dynamic binding capacities did not change significantly over a wide range of residence times. Finally, the excellent separation efficiency and potential reusability of the membrane were confirmed by five consecutive cycles of mAb capture from its cell culture harvest. The present work provides significant evidence that this weak cation-exchange nonwoven fabric platform might be a suitable alternative to packed resin chromatography for low-cost, higher productivity manufacturing of therapeutic mAbs and antibody fragments.
Highlights
We developed a weak cation-exchange membrane by attaching iminodiacetic acid (IDA) onto a poly(butylene terephthalate) (PBT) nonwoven membrane that was modified by UV grating of glycidyl methacrylate (GMA)
The UV grafting of GMA resulted in a uniform, conformal coating around each individual PBT fiber, providing available epoxy groups for further functionalization, and an increased volume for subsequent protein binding by ion exchange
To address the issue of the high production costs in monoclonal antibodies (mAbs) production, a simple and Tocombination address the issue of the highmaterials production in mAb production, a simple and effective of inexpensive andcosts low-cost preparation methods was effective combination of inexpensive materials and low-cost preparation methods was used for the development of high performance, potentially single-use disposable, weak used for the development of high performance, potentially single-use disposable, weak cation-exchange membranes for product capture, using IDA as ligand
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The results were membranes that exhibited high protein-binding capacity and a significant potential to realize single-use membrane capture chromatography [28,33]. A strong cation-exchange (CEX) membrane with sulfonic acid as ligand (CEX-SO3 membrane) was fabricated based on a PBT nonwoven and exhibited an excellent protein-binding capacity of 712.9 mg human polyclonal immunoglobulin. We expected that the IDA, which harbors two charged carboxyl groups, could endow the membrane with high protein-binding capacity while enhancing the hydrophilicity of the polyGMA grafted membrane and result in excellent flow permeability. This work illustrates the potential of high-capacity, weak cation-exchange membranes to meet the current demand for novel product capture steps for mAbs production
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