Submicrometer silica particles for high-throughput separations of protein pharmac

描述(申请人提供)：建议的研究是为了提高蛋白质分离的每分钟分辨率。更快的蛋白质分离对于开发和配制蛋白质药物至关重要，因为分离是瓶颈。蛋白质，特别是单抗，作为一类候选药物正在迅速发展。蛋白质药物具有更高的特异性和更少的不良反应，但蛋白质的异质性会导致免疫原性。为了分析异质性，需要进行分离。现有分离的低吞吐量减缓了蛋白质生产和药物配方的优化。这项提议是通过引入由具有低吸附表面的亚微米颗粒组成的极其高效的分离介质来显著提高产量。蛋白质药物必需的三种主要分离类型是 介绍：1)用于检测微小质量变化的反相层析，2)用于表征糖基化的亲水相互作用层析，以及3)用于评估聚集的流体动力学层析。这些分离将用礼来公司提供的治疗性单抗进行测试。这项研究的结果将是加快药物开发，提高治疗性单抗和其他蛋白质药物的药物安全性。这项使能技术将广泛惠及健康科学领域的研究，包括自上而下的蛋白质组学、蛋白质生物标记物的发现以及疾病机制的基础研究。 与公共健康相关：这项研究将加快使用生物技术制造的药物的开发。

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.