The proposed research is to increase the resolution per minute for protein separations. Faster protein separations are crucial to developing and formulating protein drugs because the separations are the bottleneck. Proteins, particularly monoclonal antibodies, are growing rapidly as a class of candidates in the pharmaceutical pipeline. Protein drugs promise higher specificity with fewer adverse effects, but protein heterogeneity can cause immunogenicity. Separations are required to analyze for heterogeneity. The low throughput of existing separations slows the optimizing of both protein production and drug formulation. The proposal is to increase throughput significantly by introducing extremely efficient separation media made of submicrometer particles with low-adsorptivity surfaces. Three major types of separations essential for protein drugs are addressed: 1) reversed phase chromatography for detecting small mass changes, 2) hydrophilic interaction chromatography for characterizing glycosylation, and 3) hydrodynamic chromatography for assessing aggregation. These separations will be tested with therapeutic monoclonal antibodies provided by Eli Lilly. The outcome of the research will be to speed drug development and advance drug safety for therapeutic monoclonal antibodies and other protein drugs. The enabling technology will broadly benefit research in the health sciences, including top-down proteomics, protein biomarker discovery, and basic research on disease mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM101464-04
Application #
8903976
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Edmonds, Charles G
Project Start
2012-04-01
Project End
2016-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
4
Fiscal Year
2015
Total Cost
$275,082
Indirect Cost
$85,082
Name
Purdue University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
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Zhang, Zhaorui; Wu, Zhen; Wirth, Mary J (2013) Polyacrylamide brush layer for hydrophilic interaction liquid chromatography of intact glycoproteins. J Chromatogr A 1301:156-61

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