Technology-enhanced biopharmaceuticals discovery and manufacturing (TBioDM)

技术增强的生物制药发现和制造 (TBioDM)

• 批准号: 485321-2015
• 负责人: Wilson, Derek
• 金额: $ 16.03万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=619396
• 关键词: Technology; enhanced; biopharmaceuticals; discovery; manufacturing

The global pharmaceuticals industry is in a period of fundamental transition, moving rapidly from predominantly small molecule drugs to biological macromolecules (biopharmaceuticals). Today, for instance, 72% of Sanofi Pasteur's research and development projects are biopharmaceuticals. 'Discovery Phase' processes - in which it is determined if candidate molecules exhibit a target interaction - have largely adapted to this shift, however, this has only exacerbated an emerging problem: Biological macromolecules are fundamentally more challenging to characterize than small molecule drugs, so that when early-stage candidates are identified, it is exceedingly difficult to provide a rationale for further development based on a thorough understanding of the candidate, its complexation characteristics and its effect on living systems. This 'characterization gap', in which candidates are known to exhibit the desired interaction but nothing is known about the nature of the interaction (or often even the candidate itself), is a critical bottleneck in biopharmaceuticals development. It is also a significant risk to pharmaceutical companies who must make advancement decisions based on limited bioanalytical data. New technologies are emerging from research at York University that could close the characterization gap. These include tools capable of rapid, detailed structure and conformational stability analyses, quantitative measurements of binding interactions and comprehensive determinations of biopharmaceutical effects on living systems. The proposed research is aimed at the development and adaptation of these unique tools for characterization of 'real-world' biopharmaceuticals in industrial workflows. The program combines technologies and expertise from York, biopharmaceuticals from Sanofi Pasteur and cutting-edge analytical platforms from Sciex and Fluidigm Canada to deliver a complete solution to the 'characterization gap' bottleneck in biopharmaceuticals development.

全球制药行业正处于一个根本性的转型时期，从主要的小分子药物迅速转向生物大分子（生物制药）。例如，如今赛诺菲巴斯德72%的研发项目都是生物制药。“发现阶段”过程-其中确定候选分子是否表现出靶相互作用-在很大程度上适应了这种转变，然而，这只会加剧一个新出现的问题：生物大分子从根本上说比小分子药物更难表征，因此当鉴定出早期候选药物时，在彻底了解候选物、其络合特性及其对生命系统的影响的基础上，很难为进一步的开发提供理论依据。这种“表征差距”，即已知候选物表现出所需的相互作用，但对相互作用的性质（或通常甚至候选物本身）一无所知，是生物制药开发的关键瓶颈。这对制药公司来说也是一个重大风险，因为他们必须根据有限的生物分析数据做出推进决策。约克大学的研究正在出现新技术，这些技术可以缩小表征差距。这些工具包括能够快速，详细的结构和构象稳定性分析，定量测量结合相互作用和全面确定生物制药对生命系统的影响。拟议的研究旨在开发和适应这些独特的工具，用于表征工业工作流程中的“现实世界”生物制药。该计划结合了约克的技术和专业知识，赛诺菲巴斯德的生物制药以及Sciex和Fluidigm Canada的尖端分析平台，为生物制药开发中的“表征差距”瓶颈提供完整的解决方案。