ESTABLISHMENT OF A NATIONAL GENE VECTOR LABORATORY

说明：说明申请的广泛、长期目标和具体目标，并参考项目与健康相关的内容。描述 简明扼要地介绍实现这些目标的研究设计和方法。避免总结过去的成就和使用第一人称。此描述 是为了在脱离应用程序时对提议的工作进行简洁而准确的描述。如果应用程序得到资助，则此描述， 原封不动，将成为公开信息。因此，不包括专有/机密信息。不要超过所提供的空间。 本申请建议在Beckman建立一个双重用途的NGVL“媒介生产设施” 希望之城研究所(COH)。该设施将作为生产质粒DNA的主要场所- 基于矢量，在不增加NGVL资源的情况下，提供后备生产能力和 腺病毒载体。该设施已经生产出了FDA审查的质粒物，已用于人类 临床研究，目前有三个额外的质粒产品在生产中。工作人员有丰富的经验 以及在生产符合cGMP的生物制剂供人类临床使用方面的专业知识。主任、协理主任 和QA官员具有生物技术行业的背景，具有监管事务、产品和流程方面的专业知识 开发、制造、质量体系和分子生物学、病毒学、血液学、细胞生物学和流程 细胞学。在卫生部的资助下，目前正在扩大现有流程。该设施的运营地点为 根据cGMP生产第I/I1期生物制剂和各种设施系统 已实施和正在进行的主验证计划。COH生物医学和遗传学中心(CBG)，在那里 拟建的NGVL将定位，目前生产重组单抗、质粒DNA、病毒载体和 体外操纵的细胞产品。CBG是一座专门建造的两层楼高2万平方米的建筑。英国《金融时报》COH园区内的建筑 约9,000平方英尺。英国《金融时报》机密的制造空间。剩余的空间包括部门 办公室。QC实验室和设施系统。CBG的员工完全管理和运营这座耗资1200万美元的工厂。这个 这里请求的NGVL支持将提供资源，以生产最多15个临床级别的质粒产品和 每年相关的主细胞库，以及每年最多3-4个腺病毒载体产品的能力。COH是 目前为建立293个主细胞库和工作细胞库提供资金，这些细胞库将用于NGVL 生产活动。CBG内的所有活动都通过全面的质量体系进行监控和记录 根据cGMP的说法。CBG支持将基于学术的技术转化为临床环境，并已 对该设施做出重大承诺，支持重组蛋白、病毒的开发和生产 以及用于I/II期临床研究的非病毒载体、疫苗和体外操纵细胞产品。 演出现场(S)(组织、市、州) 贝克曼希望之城研究所 杜阿尔特东路1450号 加利福尼亚州杜阿尔特，91010-3000 关键人员。请参阅第11页上的说明。根据需要使用续页以如下所示的格式提供所需信息。 命名项目中的组织角色 拉里·A·Couture，博士，贝克曼COH研究所所长 大卫·L·迪朱斯托，COH贝克曼研究所副所长，博士 小灵通398(4/98版)第2页BB 在整个应用程序中，在底部连续编号页面。不要使用3a、3b等后缀。 CC负责人/项目总监(最后、第一、中间)： 在每一张打印页和每一页的顶部输入首席调查员/项目主任的姓名。(有关类型规格，请参阅 第6页上的说明。) 研究补助金

DESCRIPTION: State the application's broad,TffTt|-term objectives and specific aims, making reference^Fthe health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. This application proposes the establishment of a dual-purpose NGVL "vector production facility" at the Beckman Research Instituteof the City of Hope (COH). The facility will serve as the primary site for production of plasmid DNA- based vectors and, without additionalNGVL resources, provide back-up production capacity and capability for adenovirus based-vectors. The facility has produced FDA-reviewed plasmid material that has been used in human clinical studies and currently has three additionalplasmid products in production. The staff has significant experience and expertise in the production of cGMP-compliant biologies for human clinical use. The Director, Associate Director and QA Officer have backgrounds in the biotechnology industry with expertise in regulatory affairs, product and process development, manufacturing, quality systems and molecular biology, virology, hematology, cell biology and flow cytometry. Scale-up of current processes is under way with funding from the COH. The facility is operated in accordance with cGMP for production of phase I/I1 biologies and the various facility systems are subject to an implemented and ongoing Master Validation Plan. The COH's Center for Biomedicine and Genetics (CBG), where the proposed NGVL will be located, currently produces recombinant monoclonal antibodies, plasmid DNA, viral vectors and ex-vivo manipulated cell products. The CBG is a purpose-built, two-story 20,000 sq. ft. building on the COH campus with approximately 9,000 sq. ft. of classified manufacturing space. The remaining space includes the departmental offices. QC labs and facility systems. The CBG staff completely manages and operates this $12-milHon facility. The NGVL support requested here will provide the resources to produce up to 15 clinical grade plasmid products and associated master cell banks per year plus a capacity of up to 3-4 adenoviral vector products per year. The COH is currently funding the establishment of 293 master and working cell banks that will be made available for NGVL production activities. All activitieswithin the CBG are monitored and documented through a thorough Quality System according to cGMP. The CBG supports the translation of academic-based technologies into the clinical setting and has made a significant commitment to the facility to support the development and production of recombinant proteins, viral and non-viral vectors, vaccines and ex-vivo manipulated cell products for phase I/II clinical studies. PERFORMANCE SITE(S) (organization, city, state) Beckman Research Institute of the City of Hope 1450 East Duarte Road Duarte, CA 91010-3000 KEY PERSONNEL. See instructions on Page 11. Use continuation pages as neededto provide the required information in the format shown below. Name Organization Role on Project Larry A. Couture, Ph.D. Beckman Research Institute of COH Director - PI David L. DiGiusto, Ph.D. Beckman Research Institute of COH Associate Director - Co-Pi PHS 398 (Rev. 4/98) Page 2 BB Number pages consecutively at the botton throughout the application. Do not use suffixes such as 3a, 3b. CC Principal I^fcjgator/Program Director (Last, first, middle): Type the name of the principal investigator/program director at the top of each printed page and each^Pitinuation page. (For type specifications, see instructions on page 6.) RESEARCH GRANT