Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins
AssigneeThe Regents of the University of California
InventorsJames D. Marks, Peter Amersdorfer, Ali Razai
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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.
Claims21
An isolated antibody, or antigen-binding fragment thereof, that specifically binds an epitope of a Botulinum neurotoxin type A (BoNT/A), wherein the antibody or antigen-binding fragment comprises:
- a) a VH CDR1 comprising the amino acid sequence of SEQ ID NO:107;
- b) a VH CDR2 comprising the amino acid sequence of SEQ ID NO:109;
- c) a VH CDR3 comprising the amino acid sequence of SEQ ID NO:142;
- and
- d) VL CDRs comprising:
- i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:177;
- ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:179;
- and
- ii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:212;
- or
- i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:181;
- ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:183;
- and
- ii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:215.
An isolated antibody or antigen-binding fragment that specifically binds each of A1 and A2 subtypes of BoNT/A with a Kd that is more than ten times tighter than an antibody or antigen-binding fragment that comprises
- a heavy chain variable region (VH) comprising complementarity determining regions comprising the amino acid sequence of VH CDR1 (SEQ ID NO:107), VH CDR2 (SEQ ID NO:109), and VH CDR3 (SEQ ID NO:
- 142);
- and
- a light chain variable region (VL) comprising complementarity determining regions comprising the amino acid sequence of VL CDR1 (SEQ ID NO:177), VL CDR2 (SEQ ID NO:179), and VL CDR3 (SEQ ID NO:
- 212).
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 VH CDR1 comprising the amino acid sequence of SEQ ID NO:107;
- b) a VH CDR2 comprising the amino acid sequence of SEQ ID NO:109;
- c) a VH CDR3 comprising the amino acid sequence of SEQ ID NO:142;
- and
- d) VL CDRs comprising:
- i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:177;
- ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:179;
- and
- ii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:212;
- or
- i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:181;
- ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:183;
- and
- ii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:215.
Dependencies are inferred from the claim text.