Slip Flow Chromatography

滑流色谱

• 批准号: 8782084
• 负责人: MARY J. WIRTH
• 金额: $ 50.1万
• 依托单位: BIOVIDRIA, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782084
• 关键词: Accounting; Adopted; Adverse drug effect; Antibodies; Autoimmune Diseases; Biomedical Engineering; Blood capillaries; Caliber; Chromatography; Collaborations; Column Chromatography; Crystal Formation; DNA Sequence Rearrangement; Development; Diagnostic; Diffusion; Disulfides; Drug Formulations; Drug Industry; Goals; Height; Heterogeneity; Humidity; IgG1; IgG2; IgG4; Immunoglobulin G; Length; Malignant Neoplasms; Manufacturer Name; Marketing; Measurement; Methods; Molecular; Monitor; Monoclonal Antibodies; Patients; Peptides; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Preparation; Procedures; Process; Protein Isoforms; Proteins; Reagent; Relative (related person); Reproducibility; Research; Resolution; Sampling; Silanes; Silicon Dioxide; Small Business Technology Transfer Research; Specificity; Stainless Steel; Toxic effect; Universities; Water; Width; base; capillary; commercialization; design; immunogenicity; innovation; instrument; new technology; particle; polymerization; public health relevance; reversed phase chromatography; scale up; self assembly; silane; silanol; tumor

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).

描述（由申请人提供）：普渡大学和 bioVidria, Inc. 之间的 STTR II 期合作的目标是将颠覆性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领域：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，从而显着提高蛋白质分离的分辨率和灵敏度。滑流使得如此小的颗粒能够实现高流速。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。这些药物具有很高的靶点特异性，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二硫键的乱序，从而导致患者产生免疫原性。 所提出的滑流柱将独特地解析和分离这些乱序版本，从而能够合理设计配方以降低免疫原性。第一阶段的研究重点是填充毛细管中的蛋白质和肽分离，展示了十倍窄的区域和滑流十倍的流量增强。第二阶段研究将重点扩大规模，开发直径 2.1 毫米的不锈钢填充柱。扩大规模将使客户能够将这些色谱柱与当前的商业仪器一起使用，这对于服务制药行业至关重要。第二阶段提案的具体目标是 1) 优化将 500 nm 颗粒填充到不锈钢柱中的工艺，2) 开发一种可扩展的工艺来制造具有可忽略不计的硅烷醇活性的键合相，以及 3) 开发用于解析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。我们聘请了三大公司提供样本：基因泰克 (IgG1)、辉瑞 (IgG2) 和礼来 (IgG4)。