SBIR Phase II: High-capacity membrane for fast and selective capture of mRNA

SBIR II 期：用于快速选择性捕获 mRNA 的高容量膜

• 批准号: 10325330
• 负责人: Graham Temples
• 金额: $ 97.79万
• 依托单位: PURILOGICS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325330
• 关键词: 2' -Deoxythymidine; Address; Advanced Development; Affinity; Binding; Binding Sites; Biological; Buffers; COVID-19; COVID-19 vaccine; Characteristics; Chromatography; Column Chromatography; Communicable Diseases; Consumption; Contracts; Development; Drug Design; Engineering; FDA Emergency Use Authorization; Feasibility Studies; Feeds; Genetic Transcription; Goals; Hour; In Vitro; Industrialization; Industry; Industry Collaboration; Length; Ligands; Malignant Neoplasms; Manufacturer Name; Medicine; Membrane; Messenger RNA; Oligonucleotides; Pathology; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Plant Resins; Play; Process; Production; Productivity; Public Health; RNA vaccine; Recovery; Reporting; Research; Role; Scientist; Series; Small Business Innovation Research Grant; Speed; Stream; Syringes; Technology; Testing; Therapeutic; Time; TimeLine; Translating; Vaccines; Work; base; bioprocess; commercialization; density; design; drug development; enzyme replacement therapy; experience; improved; innovation; meetings; milligram; oligo (dT); operation; performance tests; plasmid DNA; polyadenylated messenger RNA; prototype; public health relevance; residence; success; therapeutic development; tool; vaccine safety

Project Summary This SBIR Direct to Phase II project will develop the first affinity membrane for purifying mRNA with high capacity, selectivity, and throughput. mRNA medicines have the potential to address a wide variety of pathologies. FDA emergency use authorizations for two mRNA-based COVID-19 vaccines represent the dawning of a new era of mRNA therapies. However, a company pioneering mRNA medicines has revealed that the lack of high throughput purification processes is a major hurdle that must be addressed in the upscaling of industrial mRNA. Purilogics expects that commercialization of the proposed innovation will have a major impact on the development of mRNA medicines by providing high-throughput solutions to the purification challenges experienced at the discovery and industrial production scales. By reducing purification cycles from hours to minutes, the innovation will increase productivity and, by association, improve patient accessibility to mRNA vaccines and medicines. The products of this project will be first-in-market, prepacked affinity membrane multi- well plates and chromatography columns and cassettes that can rapidly isolate and purify mRNA drugs from in vitro transcription mixture. Competing products have low productivity because of the long residence times needed for purification. In addition, their capacities are extremely low for large size mRNA. In our initial study, we proved the feasibility of fabricating high productivity mRNA affinity membranes. Membrane chromatography column prototypes dramatically outperformed competing commercial products, and the productivity and reusability milestones exceeded the defined acceptance criteria for moving to Phase II. Our industry collaborator evaluated the prototypes using proprietary mRNA feed streams. The purifications were faster and attained higher mRNA recovery and similar purity compared to competing products. The Phase II aims are (i) to develop mRNA affinity membranes with increased capacity that enable reduced purification times for mRNA of all sizes; (ii) to finalize a scalable process for mRNA affinity membranes and develop prototypes, and (iii) to determine mRNA affinity membrane column operating ranges and conduct field research on prototypes through industry collaboration. In Specific Aim 1, we will systematically evaluate the roles played by synthesis conditions and membrane pore size on performance. In Specific Aim 2, we will establish a process to produce the membranes. We will fabricate a series of membrane columns, laterally fed cassettes, and multi-well membrane plate prototypes. In Specific Aim 3, Purilogics will collaborate with an industry leader to evaluate prototypes for capture step purification of mRNA at multiple scales (research/pilot/production). Market entry for new bioprocessing tools is prior to clinical phase II trials. With the majority of mRNA drugs in phase I and II clinical trials, the time to develop a high-productivity mRNA purification technology is now. The addressable market for prepacked mRNA capture-step chromatography products is expected to reach $200 million by 2026.

项目摘要 该SBIR直接进入第二阶段项目将开发第一种用于纯化mRNA的亲和膜， 容量、选择性和吞吐量。mRNA药物有可能解决各种各样的 病理学FDA对两种基于mRNA的COVID-19疫苗的紧急使用授权代表了 开启了mRNA疗法的新纪元然而，一家开创mRNA药物的公司透露， 缺乏高通量纯化工艺是在扩大规模生产中必须解决的主要障碍 工业mRNA Purilogics预计，拟议创新的商业化将产生重大影响 通过为纯化挑战提供高通量解决方案来开发mRNA药物 在发现和工业生产规模方面经验丰富。通过将净化周期从数小时减少到 分钟，创新将提高生产力，并通过关联，提高患者对mRNA的可及性 疫苗和药品。该项目的产品将是第一个在市场上，预装亲和膜多， 孔板和层析柱和盒，可以快速分离和纯化mRNA药物， 体外转录混合物。竞争产品由于停留时间长，生产率低 需要净化。此外，它们对大尺寸mRNA的容量极低。在我们最初的研究中， 证明了制备高产量mRNA亲和膜的可行性。膜色谱 柱原型显著优于竞争性商业产品，并且生产率和 可重用性里程碑超过了为进入第二阶段而定义的验收标准。我们的行业 一位合作者使用专有的mRNA进料流评估了原型。净化速度更快， 与竞争产品相比，获得了更高的mRNA回收率和相似的纯度。第二阶段的目标是（i） 开发具有增加的容量的mRNA亲和膜，其能够减少mRNA的纯化时间， （ii）最终确定mRNA亲和膜的可扩展过程并开发原型，以及（iii） 确定mRNA亲和膜柱操作范围，并对原型进行现场研究 通过行业合作。在具体目标1中，我们将系统地评估合成所发挥的作用， 条件和膜孔径对性能的影响。在具体目标2中，我们将建立一个流程， 膜。我们将制作一系列的膜柱，横向进给盒，和多孔 膜板原型。在具体目标3中，Purilogics将与行业领导者合作， 用于在多个规模（研究/中试/生产）下捕获步骤纯化mRNA的原型。进入市场 新的生物处理工具在临床II期试验之前。随着大多数mRNA药物处于I期和II期， 在临床试验中，现在是开发高生产率mRNA纯化技术的时候了。可寻址 到2026年，预包装mRNA捕获步骤色谱产品的市场预计将达到2亿美元。