Alternative downstream processes for production of antibodies and antibody fragments

作者：Arakawa Tsutomu^*; Tsumoto Kouhei; Ejima Daisuke

来源：Biochimica et Biophysica Acta-Proteins and Proteomics, 2014, 1844(11): 2032-2040.

DOI：10.1016/j.bbapap.2014.05.005

• Chromatography
• Protein-L
• Mixed-mode
• Arginine
• Virus inactivation

Protein-A or Protein-L affinity chromatography and virus inactivation are key processes for the manufacturing of therapeutic antibodies and antibody fragments. These two processes often involve exposure of therapeutic proteins to denaturing low pH conditions. Antibodies have been shown to undergo conformational changes at low pH, which can lead to irreversible damages on the final product. Here, we review alternative downstream approaches that can reduce the degree of low pH exposure and consequently damaged product. We and others have been developing technologies that minimize or eliminate such low pH processes. We here cover facilitated elution of antibodies using arginine in Protein-A and Protein-G affinity chromatography, a more positively charged amidated Protein-A, two Protein-A mimetics (MEP and Mabsorbent), mixed-mode and steric exclusion chromatography, and finally enhanced virus inactivation by solvents containing arginine. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody.

• 出版日期2014-11
• 单位河北医科大学