Fully Human Anti-Anthrax Toxin MAbs: Product Development

全人源抗炭疽毒素单克隆抗体：产品开发

基本信息

批准号：
6845477
负责人：
ISRAEL LOWY
金额：
$ 486.37万
依托单位：
MEDAREX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2007-09-29
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This grant proposes to develop a fully human monoclonal antibody (HuMAb) to the anthrax protective antigen (PA) as a prophylactic and therapeutic antitoxin. We have generated a panel of anti-PA HuMAbs, from which 1 monoclonal antibody (mAb 5E8) and one backup antibody (5D5) were selected for further development. The HuMAbs were selected based on superior anthrax toxin neutralizing activity and define a neutralizing epitope on PA that has not been previously recognized. The HuMAb 5E8 affords extended survival to rabbits after inhalation of a lethal dose of anthrax spores, when administered concurrently with the exposure (prophylactic activity) and when given after the onset of clinical signs of anthrax disease (therapeutic activity). The envisioned practical usage of this antibody will be to provide rapid passive immunity to individuals at risk for exposure to Bacillus anthracis. The usage may be prophylactic in pre- or post-exposure situations, but more importantly, may have efficacy in treatment of individuals with active disease for which there is no current effective therapy. To further develop this antibody, we aim to: 1. Develop a manufacturing process including cell line development, purification and formulations strategies. 2. Manufacture sufficient GMP quantities of test article to complete Phase I clinical trials and efficacy studies in appropriate animal models. 3. Investigate the safety and efficacy in in vivo and in vitro models. Perform Phase III pivotal studies in an appropriate animal model. 4. Perform Phase I clinical trials to investigate safety and pharmacokinetics in human subject.

描述（由申请人提供）：该资助计划开发针对炭疽保护性抗原（PA）的全人单克隆抗体（HuMAb）作为预防性和治疗性抗毒素。我们已经生成了一组抗 PA HuMAb，从中选择了 1 种单克隆抗体 (mAb 5E8) 和一种备用抗体 (5D5) 进行进一步开发。 HuMAb 的选择基于卓越的炭疽毒素中和活性，并定义了 PA 上以前未被识别的中和表位。在吸入致死剂量的炭疽孢子后同时给药（预防活性）以及在炭疽病临床症状出现后给药（治疗活性），HuMAb 5E8 可延长兔子的存活时间。该抗体的预期实际用途是为有接触炭疽杆菌风险的个体提供快速被动免疫。该用途可能在暴露前或暴露后情况下起到预防作用，但更重要的是，可能对治疗目前尚无有效疗法的活动性疾病个体有效。为了进一步开发这种抗体，我们的目标是： 1. 开发生产工艺，包括细胞系开发、纯化和配方策略。 2. 生产足够的 GMP 数量的测试品，以在适当的动物模型中完成 I 期临床试验和功效研究。 3. 研究体内和体外模型的安全性和有效性。在适当的动物模型中进行 III 期关键研究。 4. 进行I期临床试验以研究人体受试者的安全性和药代动力学。