PRODUCTION OF PREPARATIVE ZIRCONIA BY SPRAY DRYING

第二阶段研究的目标是通过喷雾干燥扩大新型多孔氧化锆微球的生产规模，用于生物分子的大规模制备液相色谱。第二阶段的重点将是优化平均直径15-30微米的多孔氧化锆的生产成本，以及生产第二类100-200微米的颗粒。此外，这些氧化锆颗粒将被乙二胺-N， N'-四（甲基膦酸）（EDTPA）包裹，以产生用于纯化蛋白质的生物相容性固定相。包被的氧化锆颗粒将被装入制备型液相色谱柱中，用于单克隆抗体的大规模纯化。这些色谱柱将在成本、使用复杂性和最终产品质量方面与目前使用的大规模纯化抗体方法进行比较。在第二阶段，它将被证明，超稳定的制备氧化锆柱可以作为一个具有成本效益的替代目前使用的方法。该项目将与明尼苏达大学密切合作进行。该项目的主要好处将是开发具有成本效益的抗体纯化技术，从而使纯抗体更容易用于医学研究和临床试验。拟议的商业应用：在48亿美元的生物技术产业中，约有20%专注于治疗性蛋白质。治疗性生物技术的一个主要新兴组成部分是单克隆抗体，它可用于临床分析和癌症和艾滋病毒治疗等领域的研究。本研究将为单克隆抗体等生物医药产品的纯化提供一类新型的超稳定制备型液相色谱相。

The goal of the proposed phase II research is to scale-up the manufacture of a new class of porous zirconia micro-spheres, by spray drying, for large- scale preparative liquid chromatography of biomolecules. The focus of phase II will be to optimize the manufacture of 15-30 micron average diameter porous zirconia in terms of cost of production, as well as produce a second class of 100-200 micron particles. Further, these zirconia particles will be coated with ethylenediamine-N, N'- tetra(methylphosphonic) acid (EDTPA) to produce a bio-compatible stationary phase for the purification of proteins. The coated zirconia particles will be packed into preparative liquid chromatographic columns and used for the large-scale purification of monoclonal antibodies. These columns will be compared to currently used large scale methods of purifying antibodies in terms of cost, complexity of use and quality of final product. In phase II it will be demonstrated that ultra-stable preparative zirconia columns can be used as a cost-effective alternative to currently used methods. This project will be conducted in close collaboration with the University of Minnesota. The primary benefit of this project will be the development of cost-effective antibody purification technology, thereby making pure antibodies more readily available for medical research and clinical testing. PROPOSED COMMERCIAL APPLICATIONS: Approximately 20% of the $4.8 billion biotechnology industry is focused on therapeutic proteins. A major emerging component of therapeutic biotechnology is the monoclonal antibody which is useful for clinical assays and research in areas such as cancer and HIV treatments. This research will provide a novel class of ultra-stable preparative liquid chromatographic phase useful for the purification of bio-pharmaceutical products such as monoclonal antibodies.