Antibodies to botulinum neurotoxins

Abstract

The present disclosure provides antibodies that specifically bind to botulinum neurotoxins. The antibodies and derivatives thereof that specifically bind to the neutralizing epitopes provided herein can be used in methods to specifically bind and, in some embodiments, neutralize, botulinum neurotoxin and are therefore also useful in the treatment.

1 . An isolated antibody that cross-reacts with and specifically binds to Botulinum neurotoxin serotype BoNT/C, Botulinum neurotoxin serotype BoNT/D, Botulinum neurotoxin serotype BoNT/CD, and/or Botulinum neurotoxin serotype BoNT/DC, wherein the antibody specifically binds an epitope of a Botulinum neurotoxin that is specifically bound by an antibody comprising:
 a) a V H  comprising a CDR1, CDR2 and CDR3, wherein the CDR1, CDR2 and CDR3 are selected from a V H  of an antibody selected from the group consisting of 4C10.5, 4C10.8, 4C10.15, 4C10.17, 4C10.18, 4C10.20, and 4C10.22; and   b) a V L  comprising a CDR1, CDR2 and CDR3, wherein the CDR1, CDR2 and CDR3 are selected from a V L  of an antibody selected from the group consisting 4C10.5, 4C10.8, 4C10.15, 4C10.17, 4C10.18, 4C10.20, and 4C10.22.   
     
     
         2 . The isolated antibody of  claim 1 , wherein said antibody is selected from the group consisting of 4C10.5, 4C10.8, 4C10.15, 4C10.17, 4C10.18, 4C10.20, and 4C10.22. 
     
     
         3 .- 23 . (canceled) 
     
     
         24 . An isolated nucleic acid comprising a nucleotide sequence encoding the amino acid sequence of:
 a V H  of an antibody comprising a CDR1, CDR2 and CDR3, wherein the CDR1, CDR2 and CDR3 are present in an antibody selected from the group consisting of 4C10.5, 4C10.8, 4C10.15, 4C10.17, 4C10.18, 4C10.20, and 4C10.22; and   a V L  of an antibody comprising a CDR1, CDR2 and CDR3, wherein the CDR1, CDR2 and CDR3 are present in an antibody selected from the group consisting of 4C10.5, 4C10.8, 4C10.15, 4C10.17, 4C10.18, 4C10.20, and 4C10.22.   
     
     
         25 . The isolated nucleic acid of  claim 24 , wherein the isolated nucleic acid comprises the nucleotide sequence encoding an amino acid sequence of:
 the V H  of an antibody comprising a CDR1, CDR2 and CDR3, wherein the CDR1, CDR2 and CDR3 of the antibody are present in the V H  of the antibody 4C10.20; and   the V L  of an antibody comprising a CDR1, CDR2 and CDR3, wherein the CDR1, CDR2 and CDR3 of the antibody are present in the V L  of the antibody 4C10.20.   
     
     
         26 . A cell containing the nucleic acid of  claim 24 . 
     
     
         27 . An isolated nucleic acid comprising a nucleotide sequence encoding an amino acid sequence of a variable heavy chain (V H ) polypeptide comprising a V H  CDR1 selected from a V H  of the antibody 4C10.20, a V H  CDR2 comprising a V H  CDR2 selected from a V H  of the antibody 4C10.20, and a V H  CDR2 selected from a V H  of the antibody 4C10.20. 
     
     
         28 . A variable heavy chain (V H ) polypeptide encoded by the nucleic acid of  claim 27 . 
     
     
         29 . An isolated nucleic acid comprising a nucleotide sequence encoding an amino acid sequence of a variable light chain (V L ) polypeptide comprising a V L  CDR1 selected from a V L  of the antibody 4C10.20, a V L  CDR2 comprising a V L  CDR2 selected from a V L  of the antibody 4C10.20, and a V L  CDR2 selected from a V L  of the antibody 4C10.20. 
     
     
         30 . A variable light chain (V L ) polypeptide encoded by the nucleic acid of  claim 29 . 
     
     
         31 .- 39 . (canceled)