IMPROVED VECTORS FOR THERAPEUTIC PROTEIN PRODUCTION

潜在的生物多样性蛋白质的多样性不断增加 当我们阐明越来越多的分泌性细胞的功能时， 天然肽此外，单链抗体显示 有望作为多种疾病状态的治疗剂。 这 大量有潜力的蛋白质疗法需要改进 在用于以必要的规模生产蛋白质的方法中 对动物疗效试验和临床应用的需求。我们有 最近设计了一种基于修饰的BPV复制子的附加型载体 其可以在多种细胞中作为稳定附加体维持 包括目前用于大规模蛋白质生产的那些类型。 在本申请中，我们提出了该矢量的适应性，用于 治疗性血浆蛋白的生产。 拟议的商业应用： 哺乳动物细胞的大规模培养仍然是 治疗性蛋白质生产。如果本文所述的基于BPV的系统 可以（1）减少产生高水平生产者细胞所需的时间， 细胞系，（2）增加细胞系随时间的稳定性，或（3） 增加蛋白质的总产量，那么这个系统就可以 作为一个模块直接添加到最常用的两个系统， 蛋白质制造

The diversity of potential biotherapeutic proteins is continuously rising as we elucidate the function of an ever-increasing number of secreted natural peptides. In addition, single-chain antibodies are showing promise as therapeutic agents for a variety of disease states. This profusion of potentially promising protein therapies demands improvements in the methods used for producing proteins on the scale necessary to meet demands for efficacy trials in animals and for use in the clinic. We have recently devised an episomal vector based upon a modified BPV replicon that can be maintained as a stable episome in a wide variety of cell types, including those currently used for large-scale protein production. in this application, we propose the adaptation of this vector for use in the manufacture of therapeutic plasma proteins. PROPOSED COMMERCIAL APPLICATIONS: Large-scale culture of mammalian cells remains the work-horse of therapeutic protein production. If the BPV-based system described herein can (1) reduce the time needed to generate a high-level producer cell line, (2) increase the stability of the cell line over time or (3) increase the overall amount of protein produced, then this system could be added directly as a module to the two systems most commonly used for protein manufacturing.