# US 10,117,933 B2 · Antibodies against Clostridium difficile

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- Number: US 10,117,933 B2
- Document ID: US10117933B2
- Status: Granted
- Kind: B2
- Application number: 14/648,234
- Filed: 2013-11-29
- Published: 2015-10-15
- Granted: 2018-11-06
- Earliest claimed: 2012-11-28
- Assignees: Emergent Biosolutions Canada Inc.
- Applicants: Emergent BioSolutions Canada Inc.
- Inventors: Jody Berry; Cory Nykiforuk; Darrell Johnstone; Joyee Antony George
- Web page: https://patentgrep.com/patent/US10117933B2

## CPC

- A61K 39/40: bacterial
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/1282: Clostridium (G)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- 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
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Compositions and methods for the treatment or prevention of Clostridium difficile infection in a subject are provided. The compositions comprise antibodies to Clostridium difficile toxin B. The methods provide for administering the antibodies to a subject in an amount effective to reduce or eliminate or prevent relapse from Clostridium difficile bacterial infection.

## Claims

### Claim 1

An isolated antibody or antigen-binding portion thereof comprising a heavy chain variable region (VH) and a light chain variable region (VL),
wherein the heavy chain variable region comprises three complementarity determining regions (CDRs), CDR1, CDR2, and CDR3, having the amino acid sequences set forth in SEQ ID NOs: 126, 127, and 128, respectively, or the amino acid sequences set forth in SEQ ID NOs: 110, 127, and 128, respectively, and
wherein the light chain variable region comprises three CDRs, CDR1, CDR2, and CDR3, having the amino acid sequences set forth in SEQ ID NOs: 118, 119, and 120, respectively; and
wherein the antibody or antigen-binding portion thereof specifically binds to Clostridium difficile(C. difficile) toxin B.

### Claim 2 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, wherein the heavy chain variable region comprises the amino acid sequence SEQ ID NO: 109 and wherein the light chain variable region comprises the amino acid sequence SEQ ID NO: 101.

### Claim 3 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, wherein the heavy chain variable region comprises the amino acid sequence SEQ ID NO: 125 and wherein the light chain variable region comprises the amino acid sequence SEQ ID NO: 117.

### Claim 4 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, wherein the heavy chain variable region comprises the amino acid sequence SEQ ID NO: 141 and wherein the light chain variable region comprises the amino acid sequence SEQ ID NO: 133.

### Claim 5 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 43, and wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 35.

### Claim 6 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, wherein the dissociation constant (KD) of the antibody or antigen-binding portion thereof binding to C. difficile toxin B is less than about 8.6×10−9 M.

### Claim 7 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, which comprises an IgG constant region, IgE constant region, IgD constant region, IgM constant region, an IgA constant region, or any fragment thereof.

### Claim 8 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, which is functionally linked to another molecule.

### Claim 9 (depends on 8)

The antibody or antigen-binding portion thereof of claim 8, wherein the functionally linked molecule is an antibody, detectable agent, a cytotoxic agent, a pharmaceutical agent, a protein or peptide that mediates association with another molecule, an amino acid linker, a signal sequence, or an immunogenic carrier.

### Claim 10 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, which is humanized or chimeric.

### Claim 11 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, which is an scFv, a Fab fragment, an F(ab′)2, or a disulfide-linked Fv.

### Claim 12 (depends on 1)

A composition comprising the antibody or antigen-binding portion thereof of claim 1, and a pharmaceutically acceptable carrier.

### Claim 13 (depends on 1)

A kit comprising the antibody or antigen-binding portion thereof of claim 1 and one or more of an antibody that binds to C. difficile toxin A, a therapeutic agent, a coupling agent, a material for preparing the antibody for administration, or a pharmaceutically acceptable carrier.

### Claim 14 (depends on 13)

The kit of claim 13, further comprising: one or more of C. difficile whole toxin B, toxoid B, toxin B fragment 4, or toxin B fragment 1.

### Claim 15 (depends on 1)

A method of treating a C. difficileassociated disease (CDAD), comprising administering to a subject an effective amount of the antibody or antigen-binding portion thereof of claim 1, wherein the subject is infected, or is believed to be infected, with C. difficile.

### Claim 16 (depends on 15)

The method of claim 15, wherein the antibody or antigen-binding portion thereof is administered intravenously, subcutaneously, intramuscularly or transdermally.

### Claim 17 (depends on 15)

The method of claim 15, further comprising administering a second agent.

### Claim 18 (depends on 17)

The method of claim 17, wherein the second agent is a different antibody or antigen-binding portion thereof.

### Claim 19 (depends on 17)

The method of claim 17, wherein the second agent is an antibiotic.

### Claim 20 (depends on 19)

The method of claim 19, wherein the antibiotic is vancomycin, metronidazole, or fidaxomicin.

### Claim 21 (depends on 1)

The antibody or antigen-binding portion thereof of claim 1, wherein the antibody or antibody-binding portion thereof binds to fragment 1 of C. difficile Toxin B.

### Claim 22

An isolated antibody heavy chain variable region, wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 43, 109, 125, and 141,
wherein an antibody or antigen-binding binding portion thereof comprising the heavy chain variable region and a light chain variable region comprising the amino acid sequence SEQ ID NO: 35, 101, 117, or 133, respectively, can specifically bind to C. difficile toxin B.

### Claim 23

An isolated antibody light chain variable region, wherein the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 35, 101, 117, or 133,
wherein an antibody or antigen-binding binding portion thereof comprising the light chain variable region and a heavy chain variable region comprising the amino acid sequence SEQ ID NO: 43, 109, 125, or 141, respectively, can specifically bind to C. difficile toxin B.