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US 10,308,708 B2Granted
Antibodies that neutralize botulinum neurotoxins
AssigneeThe Regents of the University of California
InventorsJames D. Marks, Isin N. Geren
Life of this patent
Estimating the term…
Abstract
This disclosure 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.
Claims19
A composition comprising:
- a first nucleic acid comprising the isolated nucleic acid comprising a nucleotide sequence encoding a variable heavy chain (VH ) polypeptide comprising
- a VH CDR1 comprising the amino acid sequence of HYGMH (SEQ ID NO:492);
- a VH CDR2 comprising the amino acid sequence of VIWYDGRNPYYAASVKG (SEQ ID NO:494);
- and
- a VH CDR3 comprising the amino acid sequence of DLTRFHDTTFGVFEM (SEQ ID NO:496);
- and
- a second nucleic acid comprising the isolated nucleic acid comprising a nucleotide sequence encoding a variable light chain (VL ) polypeptide comprising
- a VL CDR1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:742);
- a VL CDR2 comprising the amino acid sequence of AASSLQS (SEQ ID NO:744);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSSLYT (SEQ ID NO:746);
- wherein the first and second isolated nucleic acids are on the same or different nucleic acid constructs.
9 more elements
A composition comprising:
- a first nucleic acid comprising the isolated nucleic acid comprising a nucleotide sequence encoding a variable heavy chain (VH ) polypeptide comprising
- a VH CDR1 comprising the amino acid sequence of GFTFSHYG (SEQ ID NO:1309);
- a VH CDR2 comprising the amino acid sequence of IWYDGRNP (SEQ ID NO:1310);
- and
- a VH CDR3 comprising the amino acid sequence of VKDLTRFHDTTFGVFEM (SEQ ID NO:1311);
- and
- a second nucleic acid comprising the isolated nucleic acid comprising a nucleotide sequence encoding a variable light chain (VL ) polypeptide comprising
- a VL CDR1 comprising the amino acid sequence of QGISSW (SEQ ID NO:1312);
- a VL CDR2 comprising the amino acid sequence of AAS (SEQ ID NO:1313);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSSL (SEQ ID NO:1314);
- wherein the first and second isolated nucleic acids are on the same or different nucleic acid constructs.
9 more elements
A composition comprising:
- a first nucleic acid comprising the isolated nucleic acid comprising a nucleotide sequence encoding a variable heavy chain (VH ) polypeptide comprising
- a VH CDR1 comprising the amino acid sequence of HYGMH (SEQ ID NO:492);
- a VH CDR2 comprising the amino acid sequence of VIWYDGRNPYYAASVKG (SEQ
- ID NO:494);
- and
- a VH CDR3 comprising the amino acid sequence of DLTRFHDTTFGVFEM (SEQ ID NO:496);
- and
- a second nucleic acid comprising the isolated nucleic acid comprising a nucleotide sequence encoding a variable light chain (VL ) polypeptide comprising
- a VL CDR1 comprising the amino acid sequence of RASQSISSWLA (SEQ ID NO:735);
- a VL CDR2 comprising the amino acid sequence of KASSLEN (SEQ ID NO:737);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSTYSRT (SEQ ID NO:739);
- wherein the first and second isolated nucleic acids are on the same or different nucleic acid constructs.
10 more elements
A composition comprising:
- a first isolated nucleic acid comprising a nucleotide sequence encoding a variable heavy chain (VH ) polypeptide comprising the amino acid sequence of SEQ ID NO:19;
- and
- a second isolated nucleic acid comprising a nucleotide sequence encoding a variable light chain (VL ) polypeptide comprising:
- a VL CDR1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:742);
- a VL CDR2 comprising the amino acid sequence of AASSLQS (SEQ ID NO:744);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSSLYT (SEQ ID NO:746);
- or
- a VL CDR1 comprising the amino acid sequence of QGISSW (SEQ ID NO:1312);
- a VL CDR2 comprising the amino acid sequence of AAS (SEQ ID NO:1313);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSSL (SEQ ID NO:1314);
- or
- a VL CDR1 comprising the amino acid sequence of RASQSISSWLA (SEQ ID NO:735);
- a VL CDR2 comprising the amino acid sequence of KASSLEN (SEQ ID NO:737);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSTYSRT (SEQ ID NO:739);
- or
- the amino acid sequence of SEQ ID NO:
- 55;
- or
- the amino acid sequence of SEQ ID NO:
- 54
- wherein the first and second isolated nucleic acids are on the same or different nucleic acid constructs.
21 more elements
A composition comprising:
- a first isolated nucleic acid comprising a nucleotide sequence encoding a VL polypeptide comprising the amino acid sequence of SEQ ID NO:55;
- and
- a second isolated nucleic acid comprising a nucleotide sequence encoding a VH polypeptide comprising:
- a VH CDR1 comprising the amino acid sequence of HYGMH (SEQ ID NO:492);
- a VH CDR2 comprising the amino acid sequence of VIWYDGRNPYYAASVKG (SEQ ID NO:494);
- a VH CDR3 comprising the amino acid sequence of DLTRFHDTTFGVFEM (SEQ ID NO:496);
- or
- a second isolated nucleic acid present on a nucleic acid construct, the second isolated nucleic acid comprising a nucleotide sequence encoding a VH polypeptide comprising:
- a VH CDR1 comprising the amino acid sequence of GFTFSHYG (SEQ ID NO:1309);
- a VH CDR2 comprising the amino acid sequence of IWYDGRNP (SEQ ID NO:1310);
- a VH CDR3 comprising the amino acid sequence of VKDLTRFHDTTFGVFEM (SEQ ID NO:1311);
- wherein the first and second isolated nucleic acids are on the same or different constructs.
9 more elements
A nucleic acid construct comprising:
- i) a first nucleic acid comprising a nucleotide sequence encoding an amino acid sequence of a variable heavy chain (VH ) polypeptide comprising
- a VH CDR1 comprising the amino acid sequence of HYGMH (SEQ ID NO:492);
- a VH CDR2 comprising the amino acid sequence of VIWYDGRNPYYAASVKG (SEQ ID NO:494);
- and
- a VH CDR3 comprising the amino acid sequence of DLTRFHDTTFGVFEM (SEQ ID NO:496);
- or
- a VH CDR1 comprising the amino acid sequence of GFTFSHYG (SEQ ID NO:1309);
- a VH CDR2 comprising the amino acid sequence of IWYDGRNP (SEQ ID NO:1310);
- and
- a VH CDR3 comprising the amino acid sequence of VKDLTRFHDTTFGVFEM (SEQ ID NO:1311);
- and
- ii) a second nucleic acid comprising a nucleotide sequence encoding a variable light chain (VL ) polypeptide comprising:
- a VL CDR1 comprising the amino acid sequence of RASQGISSWLA (SEQ ID NO:742);
- a VL CDR2 comprising the amino acid sequence of AASSLQS (SEQ ID NO:744);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSSLYT (SEQ ID NO:746);
- or
- a VL CDR1 comprising the amino acid sequence of QGISSW (SEQ ID NO:1312);
- a VL CDR2 comprising the amino acid sequence of AAS (SEQ ID NO:1313);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSSL (SEQ ID NO:1314) or
- a VL CDR1 comprising the amino acid sequence of RASQSISSWLA (SEQ ID NO:735);
- a VL CDR2 comprising the amino acid sequence of KASSLEN (SEQ ID NO:737);
- and
- a VL CDR3 comprising the amino acid sequence of QQYSTYSRT (SEQ ID NO:739).
22 more elements
Dependencies are inferred from the claim text.