FAS LIGAND AS AN IMMUNOSUPPRESSIVE AGENT

描述：(改编自申请人的摘要)初步研究由 几个团体，包括部分由第一阶段SBIR奖资助的团体 R43-AI40394给Ceres制药公司，已经展示了 以FasL为基础的预防移植排斥反应治疗自身免疫 用于治疗疾病、诱导免疫耐受和治疗癌症。“使用” 抑制T淋巴细胞介导的免疫反应的Fas配体“受 美国专利号5,759,536。发明家唐纳德·贝尔格鲁和理查德·C·杜克。 Ceres和一家大型跨国制药公司是独家 这项技术的授权者。此第二阶段应用程序的总体目标是 开发并在小鼠身上进行临床前试验，以实现商业上的实用 重组哺乳动物表达载体、腺病毒和逆转录病毒基因 编码FasL的治疗载体。这些载体及其应用策略， 将被授权给现有的制药和生物技术公司使用 在#年向FDA提交调查性新药申请 预期在人体上启动I期临床试验。具体来说， 它们将：1)产生重组哺乳动物表达载体、腺病毒和 编码突变形式的鼠和人FasL的逆转录病毒载体；2)检测 已经或将在临床前生成的载体的数量 在老鼠身上进行移植试验；以及3)对他们制造的载体进行许可。或将 向具有执行人的能力的商业实体生成 临床试验。 建议的商业应用： 有无数的商业适应症表明安全有效 自身免疫性移植用免疫抑制和/或抗炎药 以及其他炎症性疾病的指征。目前使用的药物环孢素A 和皮质类固醇类似物，广泛使用，但有许多副作用 与短期和长期给药有关。

DESCRIPTION: (Adapted from the applicant's abstract) Preliminary studies by several groups, including those funded in part by the phase I SBIR award R43-AI40394 to CERES Pharmaceuticals, have demonstrated the potential for FasL-based therapy to prevent transplantation rejection, to treat autoimmune disease, to induce immunological tolerance, and to treat cancer. The "Use of Fas Ligand to Supress T-lymphocyte Mediated Immune Response" is protected by U.S. Patent No. 5,759,536. Donald Bellgrau and Richard C. Duke, inventors. CERES and a large, multinational pharmaceutical company, are the exclusive licensees of this Technology. The overall goal of this phase II application is to develop, and test in pre-clinical trials in mice, commercially useful recombinant mammalian expression plasmid, adenoviral and retroviral gene therapy vectors encoding FasL. These vectors, and strategies for their application, will be licensed to existing pharmaceutical and biotechnology companies for use in filing Investigational New Drug IND) applications with the FDA in anticipation of initiation of phase I clinical trials in humans. Specifically, they will: 1) Generate recombinant mammalian expression plasmid, adenoviral and retroviral vectors encoding mutant forms of mouse and human FasL; 2) Test each of the vectors that have been made, or will be generated, in pre-clinical transplant trials in mice; and 3) License the vectors they have made. Or will generate, to commercial entities with the capability of carrying out human clinical trials. PROPOSED COMMERCIAL APPLICATION: There are innumerable commercial indications for a safe and effective immunosuppressive and/or anti-inflammatory agent for transplantation, autoimmune and other inflammatory disease indications. The currently used drugs, cyclosporin A and corticosteroid analogs, enjoy widespread use but have numerous side effects associated with both short and long-term administration.