Technologies to enable automated manufacturing of validated pharmaceutical hits****

新药的开发是一项非常缓慢和昂贵的工作，包括一系列容易发生风险的步骤。制药行业的最终目标是将药物开发的早期阶段转变为自动化制造过程。组合方法可以说是实现这一目标的最有前途的手段。这种方法从生产包含十亿种不同化合物的组合库开始，然后逐步减少到筛选命中，验证命中，临床前先导，临床候选药物，最终批准药物。获得一个单一的批准药物需要数千个验证的命中-化合物与确认的结合到一个治疗目标。所需的大量经验证的命中需要其自动化制造。目前，经过验证的命中是通过研究级流程的组合产生的，这些流程无法简化为制造流程。在这里，我们建议通过开发一种基于强大工艺的颠覆性技术来解决这一瓶颈，该技术将促进经验证的药物命中的自动化制造。该项目将由一个跨学科学术小组（约克大学的Krylov和Hili小组）与两家制药公司（Alphora Research和GSK Canada）和一家仪器开发公司（SCIEX）合作实施。这3家公司参与了可行性研究，促成了5项联合出版物、2项专利申请和1项发明披露。该项目预计将产生：（一）在几个相关的研究领域的新知识，（二）高度使实用技术，和（三）行业要求的技能，为学员。开发的技术将通过向支持组织和其他公司（可能包括一家分拆公司）发放许可证进行商业化。学员将由支持公司和其他技术许可方雇用。使用拟议的制造技术不仅会带来经济效益，而且由于更快地推出新药，也会带来健康效益。

Development of new drugs is a very slow and expensive undertaking that includes a sequence of risk-prone steps. The ultimate goal of the pharmaceutical industry is to transform early stages of drug development into an automated manufacturing process. The combinatorial approach is arguably the most promising means of achieving this goal. This approach starts with production of a combinatorial library, containing a billion different compounds, and followed by its step-by-step reduction to screening hits, validated hits, pre-clinical leads, clinical candidates, and, eventually, an approved drug. Obtaining a single approved drug requires thousands of validated hits -- compounds with confirmed binding to a therapeutic target. The very large number of required validated hits necessitates their automated manufacturing. Currently, validated hits are generated via a combination of research-grade processes, which cannot be streamlined into a manufacturing flow. Here we propose to resolve this bottleneck via development of a disruptive technology built upon robust processes that will facilitate automated manufacturing of validated pharmaceutical hits. The project will be carried out by an interdisciplinary academic team (Krylov's and Hili's groups at York University) in collaboration with two pharmaceutical companies (Alphora Research and GSK Canada) and an instrumentation-development company (SCIEX). The 3 companies participated in the feasibility study, which led to 5 joint publications, 2 patent applications, and an invention disclosure. The project is expected to generate: (i) new knowledge in several related areas of research, (ii) a highly-enabling practical technology, and (iii) industry-demanded skills for the trainees. The developed technology will be commercialized via licensing to the supporting organizations and other companies, potentially including a spin off company. Trainees will be hired by the supporting companies and other technology licensors. The use of the proposed manufacturing technology will lead not only to economic benefits but also to health benefits due to the faster introduction of new drugs.**********