Bioengineered Recombinant FVIII

生物工程重组 FVIII

• 批准号: 8647463
• 负责人: Gabriela Denning
• 金额: $ 80.99万
• 依托单位: EXPRESSION THERAPEUTICS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8647463
• 关键词: Adolescence; Anabolism; Animal Model; Biochemical; Biological Products; Biomanufacturing; Biomedical Engineering; Bioreactors; Blood Coagulation Factor; Breathing; Capital; Cell Culture Techniques; Cell Line; Cells; Clinical; Complex; Development; Development Plans; Disease; Documentation; Dose; Endoplasmic Reticulum; Ensure; Factor VIII; Family suidae; Feedback; Fermentation; Glycoproteins; Goals; Golgi Apparatus; Growth; HIV; Half-Life; Hamsters; Healthcare; Hemophilia A; Human; Intellectual Property; Investigational Drugs; Investigational New Drug Application; Kidney; Kilogram; Legal patent; M cell; Mammalian Cell; Marketing; Messenger RNA; Methods; Modeling; Performance; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacology and Toxicology; Pharmacy facility; Phase; Plasma; Post-Translational Protein Processing; Preparation; Price; Process; Production; Productivity; Property; Proteins; Recombinant Proteins; Recombinants; Records; Recovery; Reference Standards; Regulatory Affairs; Replacement Therapy; Rodent; Running; Safety; Serum; Serum-Free Culture Media; Small Business Innovation Research Grant; Suspension substance; Suspensions; System; Technology; Technology Transfer; Testing; Therapeutic; Toxic effect; Transgenes; Virus; base; biophysical techniques; commercialization; cost; cost effective; density; design; experience; human F8 protein; improved; innovation; manufacturing process; manufacturing process development; meetings; mortality; novel; operation; pre-clinical; preclinical safety; public health relevance; recombinant antihemophilic factor VIII; response; scale up; technology development

PROJECT SUMMARY/ABSTRACT The manufacturing of recombinant coagulation factor VIII is a complex, labor and capital intensive endeavor. Of the recombinant proteins currently marketed, coagulation factor VIII is manufactured with the lowest efficiency and is by far the most expensive on a per unit mass basis with a pharmacy price of $10,000,000 per gram. The goal of the current application is to develop a product technology and a manufacturing process that can improve the production volume and pharmacy price of factor VIII biologics. Expression Therapeutics has developed and patented two technologies, a bioengineered factor VIII transgene that demonstrates 100-fold greater expression than standard human factor VIII, and a high performance baby hamster kidney-derived (BHK) cell line, designated BHK-MS, that can be cultured and expanded indefinitely and at high density in serum-free medium under suspension bioreactor conditions. In the current application, we propose to complete pre-clinical manufacturing, product characterization and pharmacology and toxicity studies necessary to submit an Investigational New Drug application.

项目概要/摘要 重组凝血因子 VIII 的生产是一项复杂的、劳动力和资本密集型的​​工作。 在目前市售的重组蛋白中，凝血因子 VIII 的制造成本最低 效率高，并且是迄今为止每单位质量最昂贵的，药房价格为每单位 10,000,000 美元 克。当前应用的目标是开发一种产品技术和制造工艺， 可以提高VIII因子生物制剂的产量和药价。表达疗法有 开发了两项技术并获得专利，其中一项是生物工程因子 VIII 转基因，其效果可提高 100 倍 比标准人类因子 VIII 更高的表达，以及高性能的小仓鼠肾源性 (BHK) 细胞系，命名为 BHK-MS，可以在 悬浮生物反应器条件下的无血清培养基。在当前的应用程序中，我们建议完成 需要提交的临床前生产、产品表征以及药理学和毒性研究 新药研究申请。