Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins

Patent metadata

Field	Value
Publication number	US-9181330-B2
Application number	US-201314035619-A
Country	US
Kind code	B2
Filing date	Sep 24, 2013
Priority date	Mar 22, 2007
Publication date	Nov 10, 2015
Grant date	Nov 10, 2015

Abstract

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.

First claim

What is claimed is:

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 .

Assignees

• Univ California

Inventors

• Marks James D
• Garcia Maria Consuelo

Classifications

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K16/1282 Primary

  Clostridium (G) · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title