Submicrometer silica particles for high-throughput separations of protein pharmac

描述（由申请人提供）：拟定研究旨在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，特别是单克隆抗体，作为一类候选药物正在迅速增长。 蛋白质药物具有更高的特异性和更少的副作用，但蛋白质异质性可能导致免疫原性。 需要分离以分析异质性。 现有分离的低通量减慢了蛋白质生产和药物制剂的优化。 该建议是通过引入由具有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著提高通量。 蛋白质药物所必需的三种主要分离类型是 地址：1）用于检测小质量变化的反相色谱法，2）用于表征糖基化的亲水相互作用色谱法，和3）用于评估聚集的流体动力学色谱法。 将使用Eli Lilly提供的治疗性单克隆抗体检测这些分离物。 这项研究的结果将加速药物开发，提高治疗性单克隆抗体和其他蛋白质药物的药物安全性。 这项技术将广泛造福健康科学研究，包括自上而下的蛋白质组学、蛋白质生物标志物发现和疾病机制的基础研究。 公共卫生相关性：这项研究将加速利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.