# US 9,518,109 B2 · Prevention, treatment and diagnosis of P. gingivalis infection

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- Number: US 9,518,109 B2
- Document ID: US9518109B2
- Status: Granted
- Kind: B2
- Application number: 14/487,461
- Filed: 2014-09-16
- Published: 2015-03-19
- Granted: 2016-12-13
- Earliest claimed: 2008-08-29
- Assignees: Oral Health Australia Pty Ltd
- Applicants: Oral Health Australia PTY Ltd
- Inventors: Eric Charles Reynolds; Neil Martin O'Brien Simpson; Keith J Cross; Nada Slakeski
- Web page: https://patentgrep.com/patent/US9518109B2

## CPC

- C07K 14/195: from bacteria
- A61K 39/0216: {Bacteriodetes, e.g. Bacteroides, Ornithobacter, Porphyromonas}
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 31/04: Antibacterial agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/1203: Gram-negative bacteria
- C07K 16/1257: {from Bacteridaceae (F)}
- C12N 9/14: Hydrolases (3)
- C12N 9/52: derived from bacteria {or Archaea}
- C12Y 304/21: Serine endopeptidases (3.4.21)
- G01N 33/56955: {involved in periodontal diseases}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- C12Y 304/21004: Trypsin (3.4.21.4)
- C12Y 306/05002: Small monomeric GTPase (3.6.5.2)
- G01N 2333/95: Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to generation and use of cellular and humoral responses for the prevention and treatment of P. gingivalis related conditions and diseases.

## Claims

### Claim 1

A method of reducing the secerity of a P. gingivalis-related disease or condition in a subject, comprising administering to the subject an antibody raised against a chimeric or fusion protein comprising a first peptide joined directly or through a linker to a second peptide or polypeptide, wherein:
(A) said first peptide comprises a region of a P. gingivalis trypsin-like enzyme selected from the group consisting of the amino acid sequence that is the same as, or at least 90% homologous to, the sequence shown in any one of SEQ ID NOs: 1-34; and
(B) said second peptide or polypeptide is selected from the group consisting of:
(i) the amino acid sequence that is the same as, or at least 90% homologous to, the sequence of an adhesin domain of the Lys-X-proteinase of P. gingivalis shown in any one of SEQ ID NOs: 35-37 and 40-43; and
(ii) the amino acid sequence that is the same as, or at least 90% homologous to, the sequence of an adhesin domain of the Arg-X-proteinase of P. gingivalis shown in any one of SEQ ID NOs: 38-39 and 44-46;
(iii) the amino acid sequence that is the same as, or at least 90% homologous to, the sequence of a HagA adhesin domain of P. gingivalis shown in any one of SEQ ID NOs: 80-82; and
(iv) the amino acid sequence that is the same as or at least 90% homologous to, the sequence shown in any one of SEQ ID NOs: 69-79 and 83 to 85.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the first peptide of the chimeric or fusion peptide comprises or consists of a sequence shown in one of more of SEQ ID NOs. 3 to 26.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the antibody is a monoclonal antibody.

### Claim 4 (depends on 1)

The method according to claim 1, wherein:
(A) the first peptide of the chimeric or fusion protein comprises a sequence selected from the group consisting of KAS1 (SEQ ID NO: 27), KAS2 (SEQ ID NO: 28), KAS3 (SEQ ID NO: 29), PAS1K (SEQ ID NO: 30), RAS1 (SEQ ID NO: 31), RAS2 (SEQ ID NO:32), KAS3 (SEQ ID NO: 33), and PAS1R (SEQ ID NO: 34), and
(B) the second peptide or polypeptide of the chimeric or fusion protein comprises a sequence (i) selected from the group consisting of KA1 (SEQ ID NO: 35), KA2 (SEQ ID NO: 40), KA3 (SEQ ID NO: 41), KA4 (SEQ ID NO: 42), KA5 (SEQ ID NO: 43), RA1 (SEQ ID NO: 38), RA2 (SEQ ID NO: 44), RA3 (SEQ ID NO: 45), RA4 (SEQ ID NO: 46), HA1 (SEQ ID NO: 80), HA1* (SEQ ID NO: 81), HA1** (SEQ ID NO: 82), or (ii) selected from the group consisting of SEQ ID NOs. 69-79, or (iii) selected from the group consisting of SEQ ID NOs. 83-85.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the chimeric or fusion protein comprises at least two sequences that are the same as, or at least 90% homologous to, a sequence selected from the group consisting of KAS1 (SEQ ID NO: 27), KAS2(SEQ ID NO: 28), KAS3 (SEQ ID NO: 29), PAS1K (SEQ ID NO: 30), RAS1 (SEQ ID NO: 31), RAS2 (SEQ ID NO: 32), RAS3 (SEQ ID NO: 33), and PAS1R (SEQ ID NO: 34).

### Claim 6 (depends on 1)

The method according to claim 1, wherein said first peptide of the chimeric or fusion protein comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 3-34 and sequences at least 90% homologous thereto.

### Claim 7 (depends on 1)

The method according to claim 1, wherein said second peptide or polypeptide of the chimeric or fusion protein comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 35-39 and sequences at least 90% homologous thereto.

### Claim 8 (depends on 1)

The method according to claim 1, wherein:
(a) said first peptide of the chimeric or fusion protein comprises the amino acid sequence that is the same as or at least 90% homologous to the sequence shown in any one of SEQ ID NOs: 27-30 and said second peptide or polypeptide of the chimeric or fusion protein comprises the amino sequence that is the same as or at least 90% homologous to the sequence shown in any one of SEQ ID NOs: 36-37; or
(b) said first peptide of the chimeric or fusion protein comprises the amino acid sequence that is the same as or at least 90% homologous to the sequence shown in any one of SEQ ID NOs: 31-34 and said second peptide or polypeptide of the chimeric or fusion protein comprises a sequence that is the same as or at least 90% homologous to SEQ ID NO:39.

### Claim 9 (depends on 1)

The method according to claim 1, wherein said second peptide or polypeptide of the chimeric or fusion protein comprises or consists of the sequence shown in one or more of SEQ ID NOs. 69 to 79 or one or more of SEQ ID NOs. 83 to 85.

### Claim 10 (depends on 9)

The method according to claim 9, wherein said first peptide of the chimeric or fusion protein comprises or consists of the sequence shown in one of more of SEQ ID NOs. 3 to 26.

### Claim 11 (depends on 1)

The method according to claim 1, wherein said first peptide of the chimeric or fusion protein comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO:28 and said second peptide or polypeptide of the chimeric or fusion protein comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO: 37.

### Claim 12 (depends on 1)

The method according to claim 1, wherein said first peptide of the chimeric or fusion protein comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO:27 and said second peptide or polypeptide comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO:36.
