Jacob P LeBarre, Wenning Chu, Scott H Altern, Andrew J Kocot, Dipendra Bhandari, Eduardo Barbieri, Jae Sly, Michael Crapanzano, Steven M Cramer, Michael Phillips, David Roush, Ruben Carbonell, Cristiana Boi, Stefano Menegatti
The polishing step in the downstream processing of therapeutic antibodies removes residual impurities from Protein A eluates. Among the various classes of impurities, antibody fragments are especially challenging to remove due to the broad biomolecular diversity generated by a multitude of fragmentation patterns. The current approach to fragment removal relies on ion exchange or mixed-mode adsorbents operated in bind-and-gradient-elution mode. However, fragments that bear strong similarity to the intact product or whose biophysical features deviate from the ensemble average can elude these adsorbents, and the lack of a chromatographic technology enabling robust antibody polishing is recognized as a major gap in downstream bioprocessing...
February 27, 2024: Journal of Chromatography. A