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Human Antibody Therapeutics Against Anthrax

抗炭疽的人类抗体疗法

基本信息

批准号：
7111021
负责人：
Katherine S Bowdish
金额：
$ 119.47万
依托单位：
ALEXION PHARMACEUTICALS, 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：
2004-07-15 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7111021
关键词：
Bacillus anthracis Macaca fascicularis anthrax antibacterial antibody biotechnology bioterrorism /chemical warfare clinical research cooperative study dosage drug administration routes drug screening /evaluation human subject immunologic substance development /preparation laboratory rabbit military personnel monoclonal antibody pharmacokinetics

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of our research is to develop fully human antibodies as immunotherapeutics against anthrax infection in humans. Mab 83K7C and Mab 63LID are two lead candidates identified using phage display technology that protect rats in vivo against a lethal anthrax toxin challenge. These two antibodies neutralize potently via differing mechanisms. In order to determine efficacy against an inhalational anthrax infection and possibly discriminate between these candidates so as to move at least one toward therapeutic use, this application is specifically targeted to the performance of preclinical pharmacokinetic and spore challenge studies in rabbits and monkeys. If protection is shown, these studies will be used to begin to fulfill the requirements for the two animal models requested by the FDA for biodefense therapeutics that cannot undergo Phase II and Phase III clinical testing in humans for ethical reasons (21CFR 314.610 and 601.91). The project has been broken down into five specific aims. 1) Sufficient antibody must be produced and purified for the trials under consideration, and this will be performed at Kemp Biotechnologies, Inc. (Frederick, MD). Material will be analyzed and trial dosages prepared and validated by applicant. 2) Pharmacokinetic trials in rabbits will be performed at Charles River Laboratories (CRL) (Worcester, MA) to help establish appropriate dosing and route of administration for spore challenge trials. 3) Rabbit spore challenge trials will be performed at Battelle Medical Research and Evaluation Facility (MREF) (Jefferson, OH). 4) If efficacy in rabbits is demonstrated, monkey pharmacokinetic trials with one or both antibodies will be performed at CRL. 5) Spore challenge trials in monkeys will be performed at Battelle MREF. GLP conditions will be used in production and for both the pharmacokinetic and spore challenge studies such that data obtained from these trials could be acceptable for FDA submittal. If spore challenge trials in monkeys are successful, we will continue with additional preclinical and Phase I human trials outside the scope of this grant.

描述（由申请人提供）：我们研究的长期目标是开发完全人抗体作为人类炭疽感染的免疫治疗剂。Mab 83K7C和Mab 63LID是使用噬菌体展示技术鉴定的两种主要候选物，其在体内保护大鼠免受致死性炭疽毒素攻击。这两种抗体通过不同的机制有效地中和。为了确定对吸入性炭疽感染的疗效，并可能区分这些候选药物，以便将至少一种药物用于治疗用途，本申请专门针对在家兔和猴中进行临床前药代动力学和孢子挑战研究。如果显示出保护作用，这些研究将用于开始满足FDA要求的两种动物模型的要求，用于生物防御治疗，由于伦理原因不能在人体中进行II期和III期临床试验（21 CFR 314.610和601.91）。该项目分为五个具体目标。1)必须为所考虑的试验生产和纯化足够的抗体，这将在肯普Biotechnologies，Inc.进行。（Frederick，MD）。将由申请人分析材料并制备和验证试验剂量。2)将在Charles River Laboratories（CRL）（Worcester，MA）进行家兔药代动力学试验，以帮助确定孢子攻毒试验的适当剂量和给药途径。3)家兔孢子挑战试验将在Battelle Medical Research and Evaluation Facility（MREF）（Jefferson，OH）进行。4)如果证明了在兔中的疗效，则将在CRL进行一种或两种抗体的猴药代动力学试验。5)将在Battelle MREF进行猴孢子攻毒试验。GLP条件将用于生产以及药代动力学和孢子挑战研究，以便从这些试验中获得的数据可用于FDA提交。如果在猴子中进行的孢子挑战试验成功，我们将继续进行本资助范围之外的其他临床前和I期人体试验。