Human Antibody Therapeutics Against Anthrax

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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.