# US 10,500,261 B2 · Synthetic antigen constructs against campylobacter jejuni

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- Number: US 10,500,261 B2
- Document ID: US10500261B2
- Status: Granted
- Kind: B2
- Application number: 15/342,813
- Filed: 2016-11-03
- Published: 2019-06-06
- Granted: 2019-12-10
- Earliest claimed: 2014-11-05
- Assignees: The United States of America as represented by the Secretary of the Navy
- Applicants: United States of America as Represented by the Secretary of the Navy
- Inventors: Patricia Guerry; Mario Artur Monteiro; Yuening Jiao; Brittany Michele Pequegnat
- Web page: https://patentgrep.com/patent/US10500261B2

## CPC

- A61K 39/105: {Delta proteobacteriales, e.g. Lawsonia; Epsilon proteobacteriales, e.g. campylobacter, helicobacter}
- A61K 39/385: Haptens or antigens, bound to carriers
- A61P 31/04: Antibacterial agents
- C07K 16/121: Helicobacter (G); Campylobacter (G)
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- 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

The invention relates to immunogenic synthetic constructs capable of inducing an immune response against Campylobacter jejuni (C. jejuni) in a subject comprising one or more monosaccharides comprising one or more MeOPN moieties. Specifically, the invention relates to immunogenic synthetic constructs capable of inducing an immune response against C. jejuni in a subject comprising one or more MeOPN-6-Gal monosaccharides, one or more MeOPN-4-Gal monosaccharides, and/or one or more MeOPN-2-Gal monosaccharides. The invention also relates to compositions comprising the immunogenic synthetic constructs, and methods of inducing an immune response against C. jejuni in a subject comprising administering the immunogenic synthetic constructs, and/or compositions comprising the immunogenic synthetic constructs, to the subject. Methods of treating, preventing, or ameliorating a C. jejuni bacterial infection in a subject comprising administering to the subject one or more doses of immunoglobulins directed to one or more of the MeOPN moieties are also contemplated.

## Claims

### Claim 1

An immunogenic synthetic construct capable of inducing an immune response against Campylobacter jejuni (C. jejuni) in a subject, wherein said immunogenic synthetic construct comprises one or more monosaccharides comprising one or more O-methyl phosphoramidate (MeOPN) moieties, wherein said one or more monosaccharides comprising one or more MeOPN moieties is MeOPN-4-Gal.

### Claim 2 (depends on 1)

The immunogenic synthetic construct of claim 1 wherein said immunogenic synthetic construct further comprises one or more MeOPN moieties selected from the group consisting of MeOPN-2-Gal and MeOPN-6-Gal.

### Claim 3 (depends on 1, 2)

The immunogenic synthetic construct of claim 1 or claim 2 wherein said immunogenic synthetic construct is conjugated to a carrier protein.

### Claim 4 (depends on 3)

The immunogenic synthetic construct of claim 3 wherein the carrier protein contains at least one T-cell epitope.

### Claim 5 (depends on 4)

The immunogenic synthetic construct of claim 4 wherein the carrier protein is CRM197.

### Claim 6 (depends on 1, 2)

The immunogenic synthetic construct of claim 1 or claim 2 wherein the subject is a human.

### Claim 7 (depends on 1, 2)

A composition comprising the immunogenic synthetic construct of claim 1 or claim 2.

### Claim 8 (depends on 7)

The composition of claim 7 wherein the composition is a pharmaceutical composition.

### Claim 9 (depends on 8)

The composition of claim 8 wherein said pharmaceutical composition is a vaccine formulation.

### Claim 10 (depends on 9)

The composition of claim 9 wherein the vaccine formulation further comprises an immune-effective amount of one or more adjuvants.

### Claim 11 (depends on 10)

The composition of claim 10 wherein the one or more adjuvants is selected from the group consisting of toll-like receptor ligands, aluminum phosphate, aluminum hydroxide, monophosphoryl lipid A, liposomes, and derivatives and combinations thereof.

### Claim 12 (depends on 7)

The composition of claim 7 wherein the composition further comprises one or more additional immunoregulatory agents.

### Claim 13 (depends on 12)

The composition of claim 12 wherein the one or more additional immunoregulatory agents is a substance selected from the group consisting of antigens of one or more strains of C. jejuni, antigens of ETEC, Shigella lipopolysaccharide structures, and unconjugated carrier proteins.

### Claim 14 (depends on 7)

The composition of claim 7 wherein the subject is a human.

### Claim 15 (depends on 1, 2)

A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the immunogenic synthetic construct of claim 1 or claim 2.

### Claim 16 (depends on 15)

The method of claim 15 wherein the subject is human.

### Claim 17 (depends on 7)

A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the composition of claim 7.

### Claim 18 (depends on 17)

The method of claim 17 wherein the subject is human.

### Claim 19 (depends on 8)

A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the composition of claim 8.

### Claim 20 (depends on 19)

The method of claim 19 wherein said subject is a human.

### Claim 21 (depends on 1, 2)

A method of inducing an immune response against C. jejuni in a subject, said method comprising
(a.) administering to the subject an effective amount of the immunogenic synthetic construct of claim 1 or claim 2; and
(b.) optionally administering to the subject one or more boosting doses of the immunogenic synthetic construct administered in step (a).

### Claim 22 (depends on 21)

The method of claim 21 wherein the effective amount administered in step (a) is from about 0.1 μg to about 10 mg of the immunogenic synthetic construct.

### Claim 23 (depends on 21)

The method of claim 21 wherein said method further comprises administering an immune-effective amount of one or more adjuvants with the construct in step (a) and/or step (b).

### Claim 24 (depends on 8)

A method of inducing an immune response against C. jejuni in a subject, said method comprising
(a). administering to the subject an effective amount of the composition of claim 8; and
(b). optionally administering to the subject one or more boosting doses of the composition administered in step (a).

### Claim 25 (depends on 24)

The method of claim 24 wherein the effective amount administered in step (a) is from about 0.1 μg to about 10 mg of the immunogenic synthetic construct.

### Claim 26 (depends on 24)

The method of claim 24 wherein said method further comprises administering an immune-effective amount of one or more adjuvants with the construct in step (a) and/or step (b).

### Claim 27 (depends on 19)

The method of claim 19 wherein the composition is a vaccine formulation.

### Claim 28 (depends on 24)

The method of claim 24 wherein the composition is a vaccine formulation.

### Claim 29

A method of treating or ameliorating a C. jejuni bacterial infection in a subject in need thereof comprising administering to the subject one or more doses of immunoglobulins, wherein said immunoglobulins recognize MeOPN-4-Gal and optionally recognize one or more additional MeOPN moieties, in the capsule of said C. jejuni bacteria.

### Claim 30 (depends on 29)

The method of claim 29 wherein said one or more additional MeOPN moieties are selected from the group consisting of MeOPN-2-Gal and MeOPN-6-Gal.

### Claim 31 (depends on 29, 30)

The method of claim 29 or claim 30 wherein said subject is human.
