PRODUCTION OF PREPARATIVE ZIRCONIA BY SPRAY DRYING

拟议的第二阶段研究的目标是通过喷雾干燥扩大生产一类新的多孔氧化锆微球，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从生产成本的角度优化15-30微米平均直径的多孔氧化锆的制造，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，以产生生物兼容的固定相，用于蛋白质的纯化。包覆后的氧化锆颗粒将被装入制备液相色谱柱中，用于大规模纯化单抗。这些色谱柱将与目前使用的大规模抗体纯化方法在成本、使用复杂性和最终产品质量方面进行比较。在第二阶段，将证明超稳定的制备氧化锆柱可以作为目前使用的方法的成本效益的替代方法。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测试。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抗，它对癌症和艾滋病毒治疗等领域的临床分析和研究很有用。本研究将为单抗等生物医药产品的纯化提供一种新型的超稳定制备液相。

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.