3 results about "Botulism" patented technology

Serotype E botulinum neurotoxin (BoNT / E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. However, the molecular mechanism by which BoNT / E recognizes synaptic vesicle glycoprotein 2A (SV2.A) and 2B (SV2B), but no closely related SV2C, as its neuronal receptors has been challenging to resolve. The Inventor, surprisingly, was able to obtain crystal structures of the receptor-binding domain of BoNT / E (HCE) in complex with SV2.A. These structures reveal that HCE engages both specific peptide fragments and an N-glycan of SV2A, as well as SV2B in a similar manner. Structure-based mutagenesis and functional studies demonstrate that both the peptide- and glycan-based associations are essential for SV2A / 2B-mediated cell entry of BoNT / E and for its potent neurotoxicity. Thus, the engineering of BoNT / E variants for new clinical applications is described herein.

Products, pharmaceutical compositions, methods of use, and kits are provided for treating a patient suffering from botulinum neurotoxin intoxication. Featured are single-domain variable heavy-chain (VHH) polypeptides (antibodies) that target and neutralize the light chain (LC) protease domains of botulinum neurotoxin (BoNT), i.e., BoNT LC / A and BoNT LC / B, and that advantageously provide late and post-exposure therapy for botulism patients. The LC / A toxin-binding and LC / B toxin-binding VHH polypeptides, which can be recombinantly produced, specifically bind to the LCs of the botulinum neurotoxins to inhibit toxin activity and treat intoxication.

The present disclosure provides antibodies that specifically bind to botulinum neurotoxins (e.g., BoNT / A, BoNT / B, BoNT / C, BoNT / D, BoNT / E, BoNT / F, BoNT / G, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.