Fully Human Anti-Anthrax Toxin MAbs: Product Development

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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.