SBIR Phase I: Protein A membrane columns for rapid protein purification

SBIR 第一阶段：用于快速蛋白质纯化的 Protein A 膜柱

• 批准号: 9408827
• 负责人: Jinxiang Zhou
• 金额: $ 22.25万
• 依托单位: PURILOGICS, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9408827
• 关键词: Address; Adopted; Affinity; Antibodies; Autoimmune Diseases; Binding; Biologic Development; Biological Products; Cardiovascular Diseases; Cell Culture Techniques; Cell Line; Chromatography; Chronic; Column Chromatography; Contracts; DNA; Development; Engineering; Excision; FDA approved; Goals; Hour; Industry; Industry Collaboration; Interview; Laboratories; Laws; Letters; Ligands; Malignant Neoplasms; Manufacturer Name; Medical; Medicine; Membrane; Methods; Monoclonal Antibodies; Neck; Outcome; Patients; Pharmaceutical Preparations; Phase; Plant Resins; Play; Process; Productivity; Proteins; Research; Resources; Sales; Scientist; Small Business Innovation Research Grant; Speed; System; Technology; Testing; Time; Translating; Universities; Validation; Work; commercial application; cost; cost effective; density; drug development; drug discovery; experience; improved; innovation; laboratory development; membrane synthesis; new technology; patient population; performance tests; phase 2 study; protein purification; prototype; public health relevance; research and development; residence; scale up; screening; synthetic protein; technology development

Project Summary This SBIR Phase I project is significant because it addresses a critical need for products that increase research productivity during drug discovery and development. Improving research productivity plays a key role in translating biologics from research labs to approved medications efficiently and economically. Product purification often limits the productivity, and time delays in bringing an approved medication from discovery to market can incur million dollar-per-day losses in revenue. Thus, our innovation will have a major impact on the industry since it will reduce the research and development purification cycle times from hours to minutes. Numerous campaigns are underway to develop biologics such as monoclonal antibodies (mAbs) for many chronic conditions, but the process from biologics discovery to a commercial medicine is long and expensive. Customer discovery interviews with over 130 experts in the biopharmaceutical industry suggest that new research-scale products that can isolate and purify mAbs faster and with higher capacity than the current low productivity Protein A resin chromatography products would be highly significant and impactful, as speed of the Protein A capture step purification currently is a bottle neck for biologics discovery and development. The goal of the proposed SBIR project is to prove the feasibility of developing highly productive Protein A membranes for the rapid capture step purification of mAb drugs. Products derived from this innovation will be prepacked, disposable Protein A membrane chromatography columns enabling 100 times faster capture step purification of mAbs and higher binding capacity than the current best Protein A products. To achieve this outcome, the Purilogics team will adapt a unique, proprietary membrane fabrication method pioneered by Purilogics' founder to prepare membranes with a high density of Protein A ligands. Our hypothesis is that this method will enable us to control the density of Protein A ligands, yielding high binding capacity while reducing steric hindrance to enable fast antibody binding. Key aims of the project are to synthesize and characterize Protein A membranes and to evaluate membranes for capture step purification of antibodies produced by commercial cell lines. In Specific Aim 1, systematic membrane development, characterization and screening studies will be done at Purilogics. In Specific Aim 2, comprehensive membrane performance testing using antibody cell culture supernatant will be done at three collaborator facilities: one university laboratory and two globally recognized biopharmaceutical companies. In Phase II, Purilogics will conduct membrane scale up and optimization, and work with partners to complete validation work and to develop a continuous manufacturing method for the products. Market entry will result from direct sales of these column products to purification scientists and engineers in discovery and development laboratories. The addressable market for our products is expected to reach $330 million by 2020.

项目摘要 SBIR第一阶段项目意义重大，因为它解决了对产品的迫切需求， 在药物发现和开发过程中的生产力。提高研究生产力在以下方面发挥着关键作用： 将生物制剂从研究实验室高效经济地转化为批准的药物。产品 纯化通常限制生产率，并且在将批准的药物从发现到生产的过程中存在时间延迟。 市场可能会导致每天数百万美元的收入损失。因此，我们的创新将对 因为它将把研发净化周期从数小时缩短到数分钟。 许多活动正在进行中，以开发生物制剂，如单克隆抗体（mAb），用于许多疾病。 慢性疾病，但从生物制剂发现到商业药物的过程是漫长和昂贵的。 对生物制药行业130多位专家进行的客户发现访谈表明， 研究规模的产品，可以更快地分离和纯化单克隆抗体，比目前的低容量 蛋白A树脂层析产品的生产率将是非常重要和有影响力的，因为 蛋白质A捕获纯化是目前生物制剂发现和开发的瓶颈。 SBIR项目的目标是证明开发高产蛋白A的可行性 用于mAb药物的快速捕获步骤纯化的膜。从这一创新中衍生出来的产品将 预包装的一次性蛋白A膜色谱柱，使捕获步骤快100倍 mAb的纯化和比目前最好的蛋白A产品更高的结合能力。实现这一 结果，Purilogics团队将采用独特的，专有的膜制造方法， Purilogics的创始人，以制备具有高密度蛋白A配体的膜。我们的假设是 这种方法将使我们能够控制蛋白A配体的密度，产生高结合能力，同时减少 空间位阻使得能够快速抗体结合。 该项目的主要目的是合成和表征蛋白A膜，并评估膜 用于捕获步骤纯化由商业细胞系产生的抗体。在具体目标1中，系统性 将在Purilogics进行膜开发、表征和筛选研究。在具体目标2中， 使用抗体细胞培养物上清液的全面膜性能测试将在三个月后进行。 合作机构：一所大学实验室和两家全球知名的生物制药公司。 在第二阶段，Purilogics将进行膜放大和优化，并与合作伙伴合作完成 验证工作，并开发产品的连续生产方法。市场进入将导致 从直接销售这些柱产品到纯化科学家和工程师， 开发实验室。到2020年，我们产品的潜在市场预计将达到3.3亿美元。