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Evaluation of protein engineering and process optimization approaches to enhance antibody drug manufacturability
Author(s) -
Conley Greg P.,
Viswanathan Malini,
Hou Ying,
Rank Doug L.,
Lindberg Allison P.,
Cramer Steve M.,
Ladner Robert C.,
Nixon Andrew E.,
Chen Jie
Publication year - 2011
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.23220
Subject(s) - design for manufacturability , monoclonal antibody , protein engineering , rational design , quality by design , process (computing) , computational biology , combinatorial chemistry , chemistry , amino acid , computer science , small molecule , biochemical engineering , antibody , biochemistry , nanotechnology , biology , materials science , enzyme , engineering , mechanical engineering , particle size , immunology , operating system
A potent single digit picomolar fully human monoclonal antibody (hMAb) inhibitor with a high degree of specificity to the antigen of interest was identified from a phage display library. The hMAb, however, exhibited a high degree of hydrophobicity and easily formed insoluble aggregates when purified using a Protein A based generic process. Strategies were designed using both protein engineering and process development approaches to optimize the molecule's amino acid sequence and its behavior in process conditions. The insoluble aggregation issue was brought under control by one single amino acid mutation in CDR region or by switching to non‐ProA based purification process. Our study therefore presents the rational manufacturability design for future monoclonal antibody product and its purification process under the quality by design concept by either engineering the drug molecule to adapt existing platform process or optimizing the process to fit the specific properties of the drug product. Biotechnol. Bioeng. 2011;108: 2634–2644. © 2011 Wiley Periodicals, Inc.