Instrument for Holographic Characterization of Protein Aggregates

 描述(由申请人提供)：在基于蛋白质的疗法中，对创建蛋白质三维结构至关重要的力量也是不需要的、往往是危险的蛋白质聚集体的原因。这种聚集体的存在可能意味着潜在的关键治疗产品的停产。FDA在其2014年的工业指南中建议，“对于治疗性蛋白质产品的制造商来说，尽可能地减少蛋白质聚集是至关重要的”，同时承认目前还不存在实现这一目标的技术，特别是在100 nm到100 nm的关键范围内。 10微米。蛋白质聚集几乎发生在生物制药管道的每一个阶段，从开发、配方和制造到储存和使用点。因此，对于能够评估这种大小范围内的蛋白质聚集体的大小分布和形态的仪器存在着迫切且尚未得到满足的需求。这项SBIR第一阶段计划将通过开发一种仪器来满足这一需求，该仪器使用全息视频显微镜来检测和表征药物配方中的蛋白质聚集体。这项变革性的技术最初是为了表征球形胶体和乳液滴的性质而发明的，可以足够快地测量单个团簇，用于药物样品的在线表征，并提供前所未有的独立验证的精密度和准确度。拟议的工作将修改现有的专利仪器和软件，用于测量模型系统中的蛋白质聚集，将验证该仪器区分蛋白质聚集与工业相关污染物的能力，并将展示在增强或抑制聚集的条件下监测蛋白质聚集行为的能力。蛋白质聚集的全息表征将为生物制药行业的产品开发、过程控制和质量保证提供所需的详细数据，并将在前景广阔且快速增长的蛋白质疗法领域带来更高的效率、安全性和成本节约。

 DESCRIPTION (provided by applicant): The very forces critical to creating the three dimensional structure of proteins are also responsible for unwanted and often dangerous protein aggregates in protein-­based therapeutics. The presence of such aggregates can mean the discontinuation of potentially critical therapeutic products. The FDA has advised in its 2014 Guidance for Industry that ''It is critical for manufacturers of therapeutic protein products to minimize protein aggregation to the extent possible'', while acknowledging that the technology does not currently exist to accomplish this goal, particularly in the critical range from 100 nm to 10 microns. Protein aggregation occurs at almost every stage in the biopharmaceutical pipeline, from development, formulation, and manufacturing to storage and point of use. Thus, there is a pressing and as-yet unmet need for instrumentation that can assess the size distribution and morphology of protein aggregates in this size range. This SBIR Phase I program will meet this need by developing an instrument, using holographic video microscopy to detect and characterize protein aggregates in pharmaceutical formulations. This transformative technology, originally invented to characterize the properties of spherical colloids and emulsion droplets, can measure single clusters rapidly enough to be used for in-line characterization of pharmaceutical samples, and offers unprecedented and independently verified precision and accuracy. The proposed work will modify existing patented instrumentation and software for application to the measurement of protein aggregates in model systems, will verify the instrument's ability to distinguish protein clusters from industrially relevant contaminants, and will demonstrate the ability to monitor protein-clustering behavior under conditions that enhance or inhibit aggregation. Holographic characterization of protein aggregation will provide the detailed data needed for product development, process control and quality assurance in the biopharmaceutical industry and will result in increased efficiency, safety and cost savings in the promising and rapidly growing area of protein-based therapeutics.