Submicrometer silica particles for high-throughput separations of protein pharmac

描述（由申请人提供）：拟议的研究是增加蛋白质分离的每分钟分辨率。更快的蛋白质分离是开发和配制蛋白质药物的关键，因为分离是瓶颈。蛋白质，特别是单克隆抗体，作为一类候选药物正在迅速发展。蛋白质药物具有较高的特异性和较少的不良反应，但蛋白质异质性可能导致免疫原性。需要分离来分析异质性。现有分离的低通量减慢了蛋白质生产和药物配方的优化。该建议是通过引入由低吸附性表面的亚微米颗粒制成的极其有效的分离介质来显着提高吞吐量。蛋白质药物所必需的三种主要分离类型是

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The research will speed the development of drugs made using biotechnology.