# US 11,305,002 B2 · Compositions and treatments for Haemophilus influenzae

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- Number: US 11,305,002 B2
- Document ID: US11305002B2
- Status: Granted
- Kind: B2
- Application number: 15/580,060
- Filed: 2016-06-07
- Published: 2018-10-18
- Granted: 2022-04-19
- Earliest claimed: 2015-06-09
- Assignees: The Board of Regents of the University of Oklahoma
- Applicants: The Board of Regents of the University of Oklahoma
- Inventors: Terrence L. Stull; Daniel J. Morton; Thomas W. Seale; Paul W. Whitby
- Web page: https://patentgrep.com/patent/US11305002B2

## CPC

- A61K 39/102: {Pasteurellales, e.g. Actinobacillus}, Pasteurella; Haemophilus
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 31/04: Antibacterial agents
- C07K 14/285: from Pasteurellaceae (F), e.g. Haemophilus influenza
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- 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

Immunogenic peptides, fusion polypeptides, and carrier molecules which include the immunogenic peptides, and immunogenic compositions which include these immunogenic peptides, fusion polypeptides, and/or carrier molecules bearing the peptides, and which are able to elicit antibody production against Haemophilus influenzae (Hi), are disclosed. Also disclosed are methods of their use in causing an antibody response against one or more strains of Hi.

## Claims

### Claim 1

A peptide composition, comprising a plurality of peptides comprising at least two different amino acid sequences, wherein each of the at least two different amino acid sequences is from an externally exposed loop of an outer membrane protein (OMP) selected from the group consisting of:
SEQ ID NO: 97, SEQ ID NO: 101, SEQ ID NO: 589, SEQ ID NO: 462, SEQ ID NO: 590, SEQ ID NO: 308, SEQ ID NO: 123, SEQ ID NO: 139, SEQ ID NO: 245, SEQ ID NO: 460, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 153, SEQ ID NO: 321, SEQ ID NO: 325, SEQ ID NO: 145, SEQ ID NO: 350, SEQ ID NO: 268, SEQ ID NO: 341, and SEQ ID NO: 517,
wherein each of the peptides induces an antibody response against a Nontypeable Haemophilus influenzae (NTHi), each of the peptides is linked together to form a fusion polypeptide, and a peptide at the amino-terminal end of the fusion polypeptide is duplicated at the carboxy terminal end of the fusion polypeptide.

### Claim 2 (depends on 1)

The peptide composition of claim 1, wherein the at least two different amino acid sequences are linked to a carrier molecule to form a carrier molecule composition.

### Claim 3 (depends on 1)

The peptide composition of claim 1, further defined as being able to induce an antibody response against at least one type b strain of Haemophilus influenzae.

### Claim 4 (depends on 1)

The peptide composition of claim 1, further comprising a pharmaceutically acceptable carrier, vehicle, diluent, and/or adjuvant.

### Claim 5 (depends on 1)

The peptide composition of claim 1, further defined as comprising at least five of said amino acid sequences.

### Claim 6 (depends on 5)

The peptide composition of claim 5, wherein the at least five amino acid sequences are linked to a carrier molecule to form a carrier molecule composition.

### Claim 7 (depends on 1)

The peptide composition of claim 1, wherein the at least two different amino acid sequences comprise:
SEQ ID NO: 328 from an outer membrane (OM) protein assembly factor BamA; and
SEQ ID NO: 462 and/or SEQ ID NO: 590 from an outer membrane protein P4 designated Hel.

### Claim 8 (depends on 1)

The peptide composition of claim 1, wherein the at least two different amino acid sequences comprise:
SEQ ID NO: 328 from an OM protein assembly factor designated BamA; and
SEQ ID NO: 145 from a 5′-nucleotidase designated NucA.

### Claim 9 (depends on 1)

The peptide composition of claim 1, wherein the at least two different amino acid sequences comprise:
SEQ ID NO: 328 from an OM protein assembly factor designated BamA; and
SEQ ID NO: 321 and/or SEQ ID NO: 325 from a lipopolysaccharide (LPS) assembly outer membrane (OM) complex LptDE component protein designated 1ptE.

### Claim 10 (depends on 1)

The peptide composition of claim 1, wherein the at least two different amino acid sequences comprise:
SEQ ID NO: 328 from an OM protein assembly factor designated BamA; and
SEQ ID NO: 139 from a lipoprotein designated N1pI.

### Claim 11

A peptide composition, comprising a plurality of peptides comprising at least two different amino acid sequences,
wherein each of the at least two different amino acid sequences is from an externally exposed loop of an outer membrane protein (OMP) and at least one of the amino acid sequences is SEQ ID NO: 328, and
wherein each of the peptides induces an antibody response against a Nontypeable Haemophilus influenzae (NTHi), each of the peptides is linked together to form a fusion polypeptide, and a peptide at the amino-terminal end of the fusion polypeptide is duplicated at the carboxy terminal end of the fusion polypeptide.

### Claim 12 (depends on 11)

The peptide composition of claim 11, wherein the peptide composition further comprises peptides having amino acid sequences SEQ ID NO: 462, SEQ ID NO: 590, and SEQ ID NO: 145.

### Claim 13 (depends on 11)

The peptide composition of claim 11, wherein the peptide composition further comprises peptides having amino acid sequences SEQ ID NO: 321 and SEQ ID NO: 139.

### Claim 14 (depends on 11)

The peptide composition of claim 11, wherein the peptide composition further comprises peptides having amino acid sequences SEQ ID NO: 462, SEQ ID NO: 590, SEQ ID NO: 145, SEQ ID NO: 321, and SEQ ID NO: 139.

### Claim 15

A method of inducing an immunogenic response in a subject, comprising the step of:
administering to the subject an amount of a peptide composition which is effective in stimulating an immunogenic response against Nontypeable Haemophilus influenza (NTHi) in the subject, wherein the peptide composition comprises at least two different amino acid sequences, wherein each the at least two different amino acid sequences is from an externally exposed loop of an outer membrane protein (OMP) selected from the group consisting of:
SEQ ID NO: 97, SEQ ID NO: 101, SEQ ID NO: 589, SEQ ID NO: 462, SEQ ID NO: 590, SEQ ID NO: 308, SEQ ID NO: 123, SEQ ID NO: 139, SEQ ID NO: 245, SEQ ID NO: 460, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 153, SEQ ID NO: 321, SEQ ID NO: 325, SEQ ID NO: 145, SEQ ID NO: 350, SEQ ID NO: 268, SEQ ID NO: 341, and SEQ ID NO: 517, and
wherein each of the at least two different amino acid sequences is able to induce an antibody response against NTHi, each of the peptides is linked together to form a fusion polypeptide, and a peptide at the amino-terminal end of the fusion polypeptide is duplicated at the carboxy terminal end of the fusion polypeptide.

### Claim 16 (depends on 15)

The method of claim 15, wherein the peptide composition is also effective in inducing an antibody response against at least one type b strain of Haemophilus influenzae.

### Claim 17 (depends on 15)

The method of claim 15, wherein the peptide composition comprises at least five of said amino acid sequences.

### Claim 18 (depends on 17)

The method of claim 17, wherein the at least five amino acid sequences of the peptide composition are linked to a carrier molecule to form a carrier molecule composition.