Cation-exchange displacement chromatography for the purification of recombinant protein therapeutics from variants

J Biotechnol. 1998 Dec 11;66(2-3):125-36. doi: 10.1016/s0168-1656(98)00131-x.

Abstract

Removal of low level impurities that are closely related to the bioproduct is a commonly encountered challenge in the purification of biopharmaceuticals. These separations are typically carried out by using shallow linear salt gradients at relatively low column loadings, significantly limiting the throughput of the purification process. In this manuscript we examine the utility of displacement chromatography for the purification of recombinant human brain-derived neurotrophic factor, rHuBDNF. The utility of displacement chromatography is compared to gradient elution for the removal of variants of the rHuBDNF. The results demonstrate that displacement chromatography is capable of achieving high yields and purity at high column loadings. Displacements developed on 20 microns and 50 microns cation-exchange resins are shown to provide 8-fold and 4.5-fold increases in production rates, respectively, when compared to an existing linear gradient elution operation. These results demonstrate the efficacy of displacement chromatography for the purification of therapeutic proteins from complex feed streams.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / isolation & purification*
  • Cations
  • Chromatography, Ion Exchange / instrumentation
  • Chromatography, Ion Exchange / methods*
  • Humans
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification*
  • Resins, Plant

Substances

  • Brain-Derived Neurotrophic Factor
  • Cations
  • Recombinant Proteins
  • Resins, Plant