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，包括一系列容易产生风险的步骤。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最有希望的方法。这种方法从生产一个包含10亿种不同化合物的组合文库开始，然后逐步减少到筛选目标、验证目标、临床前先导、临床候选药物，最后是批准的药物。获得一种被批准的药物需要数千种经过验证的药物，即确认与治疗靶点结合的化合物。所需的大量验证命中需要它们的自动化制造。目前，验证命中是通过研究级流程的组合产生的，无法简化为生产流程。在这里，我们建议通过开发基于稳健流程的颠覆性技术来解决这一瓶颈，该流程将促进经过验证的药物热销的自动化制造。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）合作开展。这三家公司参与了可行性研究，并发表了5篇联合出版物、2项专利申请和一项发明公开。该项目预期将产生：(i)若干有关研究领域的新知识；（ii）高度实用的技术；以及（iii）为受训者提供工业所需的技能。开发的技术将通过授权给支持组织和其他公司（可能包括一家分拆公司）实现商业化。培训生将由支持公司和其他技术许可方聘用。使用拟议的制造技术不仅会带来经济效益，而且由于更快地引入新药，还会带来健康效益。**********

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.**********