title: Alternative downstream processes for production of antibodies and antibody fragments.
abstract: 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.
authors.affiliation: Alliance Protein Laboratories, 6042 Cornerstone Court West, Suite A, San Diego, CA 9212, USA. Electronic address: tarakawa2@aol.com.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Department of Bioengineering, School of Engineering and Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.affiliation: Institute of Innovation, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ejima
keywords: Arginine; Chromatography; Mixed-mode; Protein-L; Virus inactivation