Granted Patent
B2
US 12,441,813 · App. 17/592,012 · Granted Oct 14, 2025
Antibodies for botulinum neurotoxins
Inventors:
James D. Marks (Kensington, CA); Maria Consuelo Garcia Rodriguez (San Francisco, CA); Shude Yan (San Bruno, CA)
C07K16/40C07K16/1282G01N33/56911G01N33/573A61K2039/505A61K2039/507C07K2317/20C07K2317/21C07K2317/24C07K2317/33C07K2317/54C07K2317/55C07K2317/56C07K2317/565C07K2317/622C07K2317/76C07K2317/92G01N2333/33G01N2333/952
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Abstract
The present disclosure provides antibodies that specifically bind to botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/C, BoNT/D, BoNT/E, BoNT/F, BoNT/G, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof 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 (29)
1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds a Botulinum neurotoxin (BoNT), wherein the antibody or antigen-binding fragment comprises:
a VH CDR1 comprising the amino acid sequence of NSPYFWN (SEQ ID NO:515),
a VH CDR2 comprising the amino acid sequence of YIYWSGSTNYNPSLKS (SEQ ID NO: 516),
a VH CDR3 comprising the amino acid sequence of DQGGGTVVKENWFDP (SEQ ID NO: 423),
a VL CDR1 comprising the amino acid sequence of QASQDIGKHLN (SEQ ID NO:517),
a VL CDR2 comprising the amino acid sequence of GASNLKT (SEQ ID NO:518), and
a VL CDR3 comprising the amino acid sequence of QQSYSTPPT (SEQ ID NO:519).
2. A composition comprising the isolated antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable carrier.
3. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody is a humanized antibody.
4. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody is a human antibody.
5. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody, or antigen-binding fragment thereof, is a single chain Fv (scFv), Fab, (Fab′)2 or (scFv′)2.
6. The isolated antibody, or antigen-binding fragment thereof, 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 thereof, of claim 1 .
8. A kit for specifically binding a Botulinum neurotoxin, said kit comprising: an isolated antibody, or antigen-binding fragment thereof according to claim 1 ; and a buffer.
9. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 72.
10. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 209.
11. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence SEQ ID NO: 72; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 209.
12. A composition comprising the isolated antibody, or antigen-binding fragment thereof, of claim 11 and a pharmaceutically acceptable carrier.
13. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody, or antigen-binding fragment thereof, is a single chain Fv (scFv), Fab, (Fab′)2 or (scFv′)2.
14. The isolated antibody, or antigen-binding fragment thereof, of claim 11 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 thereof, of claim 11 .
16. A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
an isolated antibody, or antigen-binding fragment thereof according to claim 11 ; and
a buffer.
17. A composition comprising:
a) a first isolated nucleic acid comprising a nucleotide sequence encoding a heavy chain variable region (VH) polypeptide comprising the amino acid sequence of SEQ ID NO: 72; and
b) a second isolated nucleic acid comprising a nucleotide sequence encoding a light chain variable region (VL) polypeptide comprising the amino acid sequence of SEQ ID NO: 209.
18. A cell comprising the first and second isolated nucleic acids of claim 17 .
19. A method of making an antibody, or antigen-binding fragment thereof, the method comprising culturing the cell of claim 18 under conditions suitable for the cell to express the antibody or antigen-binding fragment.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 21, 2022
From: MARKS, JAMES D.; FAN, YONGFENG; LOU, JIANLONG; CONSUELO GARCIA RODRIGUEZ, MARIA; YAN, SHUDE; GEREN, ISIN NEGRIZ; ZHAI, WENWU; CHAKRABORTI, SUBHENDU
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 060580/0466 →
Continuity (8)
Continuation
13813623
Provisional Application
61430084
· Jan 5, 2011
Provisional Application
61378862
· Aug 31, 2010
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