1a. Objectives (from AD-416)
The objective of this cooperative research project is to use anti-botulism monoclonal antibodies to modulate circulating toxin levels in order to identify small molecules capable of inhibiting neurotoxin activity in vivo. Initial efforts will focus on identification of small molecules suitable for inhibiting toxin serotype A.
1b. Approach (from AD-416)
PanTher Biopharma LLC is a private company focused on addressing the urgent need for new drugs to combat emerging infectious diseases and potential biowarfare agents. PanThera’s proprietary technologies and its expertise in structure-based drug design, medicinal chemistry and high throughput virtual screening will result in the development and delivery of safe, effective drugs against life-threatening diseases. PanThera has an interest in developing an effective drug for the treatment of botulisum. The USDA has a general interest in detection and prevention of foodborne botulisum. Dr. Larry Stanker, currently working in the USDA ARS Foodborne Contaminants Research Unit located in Albany, California, has developed a series of high-affinity monoclonal antibodies to botulinum neurotoxin and these have been formatted into sensitive immunoassays for detecting botulism in foods. Furthermore, many of three antibodies are capable of neutralizing toxin and rescuing animals after exposure. Combining the resources and efforts of PanThera with the ARS will produce synergistic results and further our understanding of botulinum neurotoxin. Initial research efforts by PanThera will focus on use of the USDA monoclonal antibodies as aids in identifying small molecule therapeutic drugs. Documents Trust with PanThera Biopharma LLC. Log 42695. Formerly 5325-42000-043-11T (4/11).
3. Progress Report
The Cooperator requested monoclonal anitbodies specific for different domains of botulinum neurotoxin a serotype A that were capable of neutralizing toxin in vivo. Monoclonal antibodies were generated and characterized as to their capability of neutralizing toxin in vivo using bioassays developed in this laboratory. A pair of monoclonal antibodies were selected based on their optimal toxin neutralization. These two antibodies were produced in quantity, purified, re-tested, and supplied to the Cooperator. These antibodies will be used by the Cooperator in bioassays for botulism therapeutics development.