IP Library › Granted Patent US 7,999,079
Granted Patent B2
US 7,999,079 · App. 12/646,705 · Granted Aug 16, 2011

Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins

Assignee: The Regents of the University of California
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,999,079
App. No.
12/646,705
Granted
Aug 16, 2011
Kind
B2
Abstract

This invention provides antibodies that specifically bind to and neutralize botulinum neurotoxin type A (BoNT/A) 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.

Claims (58)

1. An isolated antibody that specifically binds Botulinum neurotoxin (BoNT), or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises:

a) a V H CDR1 comprising the amino acid sequence of SEQ ID NO:33;

b) a V H CDR2 comprising the amino acid sequence of SEQ ID NO:35;

c) a V H CDR3 comprising the amino acid sequence of SEQ ID NO:63;

d) a V L CDR1 comprising the amino acid sequence of SEQ ID NO:89;

e) a V L CDR2 comprising the amino acid sequence of SEQ ID NO:91; and

f) a V L CDR3 comprising the amino acid sequence of SEQ ID NO:119.

2. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody comprises:

a heavy chain comprising the amino acid sequence of SEQ ID NO:23.

3. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody comprises:

a heavy chain comprising the amino acid sequence of SEQ ID NO:9.

4. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody comprises:

a light chain comprising the amino acid sequence of SEQ ID NO:22.

5. The isolated antibody or antigen-binding fragment thereof of claim 2 , wherein said antibody comprises:

a) a heavy chain comprising the amino acid sequence of SEQ ID NO:23; and

b) a light chain comprising the amino acid sequence of SEQ ID NO:22.

6. The isolated antibody or antigen-binding fragment thereof of claim 3 , wherein said antibody comprises:

a) a heavy chain comprising the amino acid sequence of SEQ ID NO:9; and

b) a light chain comprising the amino acid sequence of SEQ ID NO:22.

7. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody is a single chain Fv (scFv).

8. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody is an IgG.

9. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antigen-binding fragment is a Fab.

10. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antigen-binding fragment is a (Fab′) 2 .

11. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody is a (scFv′) 2 .

12. A composition comprising at least two different antibodies or antigen-binding fragments thereof that bind a Botulinum neurotoxin serotype, wherein a first antibody or an antigen-binding fragment thereof of said two different antibodies or antigen-binding fragments comprises:

a) a V H CDR1 comprising the amino acid sequence of SEQ ID NO:33;

b) a V H CDR2 comprising the amino acid sequence of SEQ ID NO:35;

c) a V H CDR3 comprising the amino acid sequence of SEQ ID NO:63;

d) a V L CDR1 comprising the amino acid sequence of SEQ ID NO:89;

e) a V L CDR2 comprising the amino acid sequence of SEQ ID NO:91; and

f) a V L CDR3 comprising the amino acid sequence of SEQ ID NO:119.

13. The composition of claim 12 , wherein said first antibody comprises:

a) a heavy chain comprising the amino acid sequence of SEQ ID NO:23; and

b) a light chain comprising the amino acid sequence of SEQ ID NO:22.

14. The composition of claim 12 , wherein said first antibody comprises:

a) a heavy chain comprising the amino acid sequence of SEQ ID NO:9; and

b) a light chain comprising the amino acid sequence of SEQ ID NO:22.

15. The composition of claim 12 , wherein a second antibody or an antigen-binding fragment thereof of said two different antibodies or antigen-binding fragments is selected from the group consisting of:

a) an antibody comprising i) a heavy chain comprising the amino acid sequence of SEQ ID NO:11 and ii) a light chain comprising the amino acid sequence of SEQ ID NO:10 or SEQ ID NO:354;

b) an antibody comprising i) a heavy chain comprising the amino acid sequence of SEQ ID NO:12 and ii) a light chain comprising the amino acid sequence of SEQ ID NO:358, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID NO:15; and

c) an antibody comprising i) a heavy chain comprising the amino acid sequence of SEQ ID NO:16 and ii) a light chain comprising the amino acid sequence of SEQ ID NO:362.

16. A kit comprising:

a composition according to any of claims 12 , 13 and 15 ; and

instructional materials teaching the use of said composition to neutralize a Botulinum neurotoxin.

17. A method of binding Botulinum neurotoxin (BoNT) in a mammal said method comprising administering to said mammal an antibody or an antigen-binding fragment thereof comprising:

a) a V H CDR1 comprising the amino acid sequence of SEQ ID NO:33;

b) a V H CDR2 comprising the amino acid sequence of SEQ ID NO:35;

c) a V H CDR3 comprising the amino acid sequence of SEQ ID NO:63;

d) a V L CDR1 comprising the amino acid sequence of SEQ ID NO:89;

e) a V L CDR2 comprising the amino acid sequence of SEQ ID NO:91; and

f) a V L CDR3 comprising the amino acid sequence of SEQ ID NO:119.

18. The method of claim 17 , wherein said antibody comprises:

a) a heavy chain comprising the amino acid sequence of SEQ ID NO:23; and

b) a light chain comprising the amino acid sequence of SEQ ID NO:22.

19. The method of claim 17 , further comprising administering a second antibody selected from the group consisting of:

a) an antibody comprising i) a heavy chain comprising the amino acid sequence of SEQ ID NO:11 and ii) a light chain comprising the amino acid sequence of SEQ ID NO:10 or SEQ ID NO:354;

b) an antibody comprising i) a heavy chain comprising the amino acid sequence of SEQ ID NO:12 and ii) a light chain comprising the amino acid sequence of SEQ ID NO:358, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID NO:15; and

c) an antibody comprising i) a heavy chain comprising the amino acid sequence of SEQ ID NO:16 and ii) a light chain comprising the amino acid sequence of SEQ ID NO:362.

Continuity (3)
Division 11342271 · Jan 26, 2006
Provisional Application 60648256 · Jan 27, 2005
Related Publication 20110171235A1 · Jul 14, 2011