Slip Flow Chromatography

描述（由申请人提供）：普渡大学和bioVidria， Inc.之间的STTR二期合作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，最大限度地发挥其影响。该产品是一种反相色谱柱，使用直径仅500 nm的二氧化硅颗粒，从而显着提高了蛋白质分离的分辨率和灵敏度。滑移流是使如此小的颗粒具有高流速的原因。主要的市场机会是分析基于单克隆抗体的生物工程药物的异质性。这些药物具有很高的靶向特异性，例如，针对肿瘤的毒性。需要解决的问题是，单克隆抗体在储存过程中会发生分子内和分子间的二硫化物置乱，导致患者产生免疫原性。所提出的滑流柱将独特地解决和分离这些混乱的版本，使配方的合理设计，以减少免疫原性。第一阶段的研究重点是蛋白质和肽在填充毛细血管中的分离，证明了10倍的狭窄区域和10倍的流动增强。第二阶段的研究将集中于扩大规模，开发直径2.1毫米的填充不锈钢柱。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期提案的具体目标是：1)优化将500 nm颗粒包装到不锈钢柱中的工艺；2)开发可扩展的工艺，使硅烷醇活性可忽略不计的键合相；3)开发分离方法，用于解决所有三种类型抗体平台的单克隆抗体的二硫重排产物。我们招募了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).