Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins
View Patent ↗This invention provides antibodies that specifically bind to and typically neutralize botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/E, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies 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.
1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds an epitope of a Botulinum neurotoxin (BoNT), wherein the antibody or antigen-binding fragment comprises:
a) a V H CDR1 comprising the amino acid sequence of SEQ ID NO:166;
b) a V H CDR2 comprising the amino acid sequence of SEQ ID NO:168;
c) a V H CDR3 comprising the amino acid sequence of SEQ ID NO:170;
d) a V L CDR1 comprising the amino acid sequence of SEQ ID NO:271;
e) a V L CDR2 comprising the amino acid sequence of SEQ ID NO:273; and
f) a V L CDR3 comprising the amino acid sequence of SEQ ID NO:275.
2. A composition comprising the isolated antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.
3. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody is a humanized antibody.
4. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody is a human monoclonal antibody.
5. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody is a single chain Fv (scFv), Fab, (Fab′) 2 or (scFv′) 2 .
6. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody is an IgG.
7. A method of specifically binding a botulinum neurotoxin in a mammal, said method comprising administering to said mammal the isolated antibody or antigen-binding fragment of claim 1 .
8. A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
a composition according to claim 1 .
9. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody comprises:
a heavy chain comprising the amino acid sequence of SEQ ID NO:52.
10. A composition comprising the isolated antibody or antigen-binding fragment of claim 9 and a pharmaceutically acceptable carrier.
11. The isolated antibody or antigen-binding fragment of claim 9 , wherein said antibody is a humanized antibody.
12. The isolated antibody or antigen-binding fragment of claim 9 , wherein said antibody is a human monoclonal antibody.
13. The isolated antibody or antigen-binding fragment of claim 9 , wherein said antibody is a single chain Fv (scFv), Fab, (Fab) 2 or (scFv′) 2 .
14. The isolated antibody or antigen-binding fragment of claim 9 , wherein said antibody is an IgG.
15. A method of specifically binding a botulinum neurotoxin in a mammal, said method comprising administering to said mammal the isolated antibody or antigen-binding fragment of claim 9 .
16. A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
a composition according to claim 9 .
17. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody comprises:
a light chain comprising the amino acid sequence of SEQ ID NO:67.
18. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody comprises:
a) a heavy chain comprising the amino acid sequence of SEQ ID NO:52; and
b) a light chain comprising the amino acid sequence of SEQ ID NO:67.
19. A composition comprising the isolated antibody or antigen-binding fragment of claim 18 and a pharmaceutically acceptable carrier.
20. The isolated antibody or antigen-binding fragment of claim 18 , wherein said antibody is a humanized antibody.
21. The isolated antibody or antigen-binding fragment of claim 18 , wherein said antibody is a human monoclonal antibody.
22. The isolated antibody or antigen-binding fragment of claim 18 , wherein said antibody is a single chain Fv (scFv), Fab, (Fab′) 2 or (scFv′) 2 .
23. The isolated antibody or antigen-binding fragment of claim 18 , wherein said antibody is an IgG.
24. A method of specifically binding a botulinum neurotoxin in a mammal, said method comprising administering to said mammal the isolated antibody or antigen-binding fragment of claim 18 .
25. A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
a composition according to claim 18 .