# US 2019/0375828 A1 · Antibodies that Neutralize Botulinum Neurotoxins

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- Number: US 2019/0375828 A1
- Document ID: US20190375828A1
- Status: Published application
- Kind: A1
- Application number: 16/389,705
- Filed: 2019-04-19
- Published: 2019-12-12
- Earliest claimed: 2008-07-31
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: James D. Marks; Jianlong Lou
- Web page: https://patentgrep.com/patent/US20190375828A1

## CPC

- C07K 16/1282: Clostridium (G)
- A61P 31/04: Antibacterial agents
- A61P 39/02: Antidotes
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim at position 1

1-45. (canceled)

### Claim 46

A composition comprising:
a) a first isolated nucleic acid comprising a nucleotide sequence encoding a variable heavy chain (VH) polypeptide comprising:
a VH CDR1 comprising the amino acid sequence of NYPMS (SEQ ID NO:520),
a VH CDR2 comprising the amino acid sequence of SLTASGDNTFYADSVKG (SEQ ID NO:522),
a VH CDR3 comprising the amino acid sequence of ALVGRYDISTGYYRPVMDS (SEQ ID NO:524); and
b) 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 RTSQGFTSALA (SEQ ID NO:770),
a VL CDR2 comprising the amino acid sequence of DASKLES (SEQ ID NO:772), and
a VL CDR3 comprising the amino acid sequence of QQSNSYPLT (SEQ ID NO:774).

### Claim 47 (depends on 46)

The composition of claim 46, wherein the first and second isolated nucleic acids are on the same nucleic acid constructs.

### Claim 48 (depends on 47)

An expression vector comprising the first and second isolated nucleic acids of claim 47.

### Claim 49 (depends on 48)

A cell comprising the expression vector of claim 48.

### Claim 50 (depends on 46)

The composition of claim 46, wherein the first and second isolated nucleic acids are on different nucleic acid constructs.

### Claim 51 (depends on 50)

A cell comprising the first and second isolated nucleic acids of claim 50.

### Claim 52 (depends on 51)

The cell of claim 51, wherein said different nucleic acid constructs are expression vectors.

### Claim 53 (depends on 51)

A method of making an antibody, or antigen-binding fragment thereof, the method comprising culturing the cell of claim 51 under conditions suitable for the cell to express the antibody or antigen-binding fragment thereof.

### Claim 54 (depends on 53)

The method of claim 53, wherein the method further comprises recovering the antibody or antigen-binding fragment thereof from the cell culture.

### Claim 55 (depends on 49)

A method of making an antibody, or antigen-binding fragment thereof, the method comprising culturing the cell of claim 49 under conditions suitable for the cell to express the antibody or antigen-binding fragment thereof.

### Claim 56 (depends on 55)

The method of claim 55, wherein the method further comprises recovering the antibody or antigen-binding fragment thereof from the cell culture.

### Claim 57 (depends on 56)

The method of claim 56, wherein the antibody, or antigen-binding fragment thereof, is a single chain variable fragment (ScFv).

### Claim 58

A composition comprising:
a) a first isolated nucleic acid comprising a nucleotide sequence encoding an amino acid sequence of a variable heavy chain (VH) polypeptide comprising an amino acid of SEQ ID NO:23; and
b) a second isolated nucleic acid comprising a nucleotide sequence encoding an amino acid sequence of a variable light chain (VL) polypeptide comprising an amino acid sequence of SEQ ID NO:59.

### Claim 59 (depends on 58)

The composition of claim 58, wherein the first and second isolated nucleic acids are on the same nucleic acid constructs.

### Claim 60 (depends on 59)

A expression vector comprising the first and second isolated nucleic acids of claim 59.

### Claim 61 (depends on 58)

The composition of claim 58, wherein the first and second isolated nucleic acids are on different nucleic acid constructs.

### Claim 62 (depends on 61)

A cell comprising the first and second isolated nucleic acids of claim 61.

### Claim 63 (depends on 62)

The cell of claim 62, wherein said different nucleic acid constructs are expression vectors.

### Claim 64 (depends on 62)

A method of making an antibody, or antigen-binding fragment thereof, the method comprising culturing the cell of claim 62 under conditions suitable for the cell to express the antibody or antigen-binding fragment thereof.

### Claim 65 (depends on 64)

The method of claim 64, wherein the method further comprises recovering the antibody or antigen-binding fragment thereof from the cell culture.

### Claim 66 (depends on 60)

A cell comprising the expression vector of claim 60.

### Claim 67 (depends on 66)

A method of making an antibody, or antigen-binding fragment thereof, the method comprising culturing the cell of claim 66 under conditions suitable for the cell to express the antibody, or antigen-binding fragment thereof.

### Claim 68 (depends on 67)

The method of claim 67, wherein the method further comprises recovering the antibody or antigen-binding fragment thereof from the cell culture.

### Claim 69 (depends on 68)

The method of claim 68, wherein the antibody, or antigen-binding fragment thereof, is a single chain variable fragment (ScFv).