Slip Flow Chromatography

描述（由申请人提供）：普渡大学和bioVidria，Inc.之间的STTR II期合作的目标是我们的目标是将颠覆性的蛋白质色谱新技术商业化，然后通过服务于制药行业增长最快的部分：蛋白质药物来最大限度地发挥其影响力。该产品是一种反相色谱柱，使用直径仅为500 nm的二氧化硅颗粒，从而显着提高蛋白质分离的分辨率和灵敏度。滑流是使这种小颗粒能够实现高流速的原因。主要的市场机会是基于单克隆抗体的生物工程药物的异质性分析。这些药物提供高靶向特异性，例如，针对肿瘤的毒性。要解决的问题是，单克隆抗体在储存过程中会发生分子内和分子间的二硫键混乱，这会在患者中引起免疫原性。 所提出的滑流柱将独特地分辨和分离这些混杂版本，从而能够合理设计制剂以降低免疫原性。第一阶段的研究集中在蛋白质和肽分离填充毛细管，展示了十倍窄区和十倍的流动增强从滑流。第二阶段的研究将集中在扩大规模，以开发直径为2.1 mm的填充不锈钢柱。扩大规模将允许客户使用这些色谱柱与当前的商业仪器，这是必不可少的服务于制药行业。II期提案的具体目的是：1）优化将500 nm颗粒填充到不锈钢柱中的工艺，2）开发可扩展的工艺，以制备具有可忽略的硅烷醇活性的键合相，3）开发用于分离所有三种类型抗体平台的单克隆抗体二硫键重排产物的分离方法。我们争取三家主要公司提供样品：基因泰克（IgG1），辉瑞（IgG2）和礼来（IgG4）。

DESCRIPTION (provided by applicant): The goal of this STTR Phase II collaboration between Purdue University and bioVidria, Inc. is to commercialize disruptive new technology for protein chromatography and then maximize its impact by serving the fastest growing segment of the pharmaceutical industry: protein drugs. The product is a reversed phase chromatography column that uses silica particles of only 500 nm in diameter, thereby significantly increasing resolution and sensitivity in protein separations. Slip flow is what enables high flow rates with such small particles. The primary market opportunity is the analysis of the heterogeneity of bioengineered drugs based on monoclonal antibodies. These drugs offer high target specificity, e.g., toxicity directed at the tumor. The problem to be solved is that monoclonal antibodies can undergo intra- and inter-molecular disulfide scrambling during storage, which causes immunogenicity in patients. The proposed slip-flow column will uniquely resolve and isolate these scrambled versions, enabling rational design of formulations to reduce immunogenicity. The Phase I research focused on protein and peptide separations in packed capillaries, demonstrating ten-fold narrower zones and a ten-fold flow enhancement from slip flow. The Phase II research will focus on scaling up to develop packed stainless steel columns of 2.1 mm in diameter. The scale-up will allow customers to use these columns with current commercial instruments, which is essential for serving the pharmaceutical industry. The Specific Aims of the Phase II proposal are to 1) optimize the process for packing 500 nm particles into stainless steel columns, 2) develop a scalable process to make bonded phases with negligible silanol activity, and 3) develop separation methods for resolving products of disulfide rearrangement of monoclonal antibodies for all three types of antibody platforms. We enlist three major companies to provide samples: Genentech (IgG1), Pfizer (IgG2) and Eli Lilly (IgG4).