US Patent 11104891 Engineered botulinum neurotoxins

Disclosed herein are modified Clostridial Botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial Botulinum serotype B, comprising one or more substitution mutations at positions corresponding 1248 or 1249 in serotype B, strain 1. Specific substitution mutations include I1248F, I1248Y, I1248H, I1248W, V1249W, V1249F, V1249Y, V1249H, I1248W/V1249F, I1248W/V1249Y, I1248W/V1249H, I1248F/V1249Y, I1248F/V1249H, I1248Y/V1249H, I1248F/V1249W, I1248Y/V1249W, I1248H/V1249W, I1248Y/V1249F, I1248H/V1249F, or I1248H/V1249Y. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.