IP Library › Patent Application 15370144
Patent Application
App. No. 15/370,144

PREVENTION, TREATMENT AND DIAGNOSIS OF P.GINGIVALIS INFECTION

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Patent No.
US None
App. No.
15/370,144
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 (37)

1 .- 70 . (canceled)

71 . A chimeric or fusion protein for inducing an immune response to P. gingivalis , the 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:

(i) part of, or all of a sequence that is the same as, or homologous to the sequence shown in SEQ ID No:1; and

(ii) part of, or all of a sequence that is the same as, or homologous to the sequence shown in SEQ ID No:2; and

(B) said second peptide or polypeptide comprises an adhesin domain of P. gingivalis , or fragment thereof, selected from the group consisting of:

(i) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Lys-X-proteinase of P. gingivalis;

(ii) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Arg-X-proteinase of P. gingivalis ; and

(iii) part of, or all of a sequence that is the same as, or homologous to the sequence of a HagA adhesin domain of P. gingivalis.

72 . The chimeric or fusion protein according to claim 71 , wherein said first peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 3-34 and sequences at least 90% homologous thereto.

73 . The chimeric or fusion protein according to claim 71 , wherein said second peptide or polypeptide comprises a sequence selected from the group consisting of SEQ ID NOs: 35-39.

74 . The chimeric or fusion protein according to claim 71 , wherein:

(a) said first peptide comprises a sequence that is the same as or homologous to a sequence selected from the group consisting of SEQ ID NOs: 27-30 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to a sequence selected from the group consisting of SEQ ID NOs: 36-37; or

(b) said first peptide comprises a sequence that is the same as or homologous to a sequence selected from the group consisting of SEQ ID NOs: 31-34 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to SEQ ID NO:39.

75 . A chimeric or fusion protein according to claim 71 , wherein:

the C-terminal residue of said first peptide is covalently linked directly or through a linker that is either (i) up to 15 amino acids in length, or (ii) less than 5 amino acids in length, to either (a) the N-terminal residue or (b) the C-terminal residue of said second peptide or polypeptide, or

the N-terminal residue of said first peptide is covalently linked directly or through a linker that is either (i) up to 15 amino acids in length, or (ii) less than 5 amino acids in length, to either (a) the N-terminal residue or (b) the C-terminal residue of said second peptide or polypeptide.

76 . A composition comprising a chimeric or fusion protein according to claim 71 .

77 . The composition according to claim 76 , further comprising an adjuvant.

78 . A method of preventing or reducing the incidence or severity of a P. gingivalis -related condition or disease in a subject, comprising administering to the subject a chimeric or fusion protein of claim 71 .

79 . An antibody raised against the chimeric or fusion protein of claim 71 .

80 . The antibody according to claim 79 , wherein the antibody is a monoclonal antibody.

81 . A method of preventing or reducing the severity of a P. gingivalis -related disease or condition in a subject, comprising administering to the subject the antibody of claim 79 .

82 . A nucleic acid molecule comprising a sequence encoding the chimeric or fusion protein of claim 71 .

83 . A method for the diagnosis or monitoring of a P. gingivalis -related condition or disease in a subject, which comprises assaying a biological sample from said subject with the chimeric or fusion protein of claim 71 to detect anti- P. gingivalis antibodies.

84 . A method for the diagnosis or monitoring of a P. gingivalis -related condition or disease in a subject, which comprises assaying a biological sample from said subject with the antibody according to claim 79 , to detect the presence of P. gingivalis.

85 . A chimeric or fusion protein according to claim 71 wherein the second peptide or polypeptide comprises or consists of a sequence shown in one or more of SEQ ID No: 69 to 79 or one or more of SEQ ID No: 83 to 85.

86 . A chimeric or fusion protein according to claim 90 wherein the first peptide comprises or consists of a sequence shown in one of more of SEQ ID No: 3 to 26 or one or more of SEQ ID No: 64 to 68.

87 . A chimeric or fusion protein for inducing an immune response to P. gingivalis , comprising:

(A) a first peptide with a sequence from a P. gingivalis trypsin-like enzyme 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), KAS4 (SEQ ID NO: 64), KAS5 (SEQ ID NO: 65), KAS6 (SEQ ID NO: 66), RAS1 (SEQ ID NO: 31), RAS2 (SEQ ID NO: 32), RAS3 (SEQ ID NO: 33), KAS4 (SEQ ID NO: 67), RAS5 (SEQ ID NO: 68), and PAS1R (SEQ ID NO: 34), and

(B) a second peptide or polypeptide comprises an adhesin domain of P. gingivalis , or fragment thereof, (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.

88 . A chimeric or fusion protein for inducing an immune response to P. gingivalis , comprising at least two sequences that are the same as, or homologous to a sequence from a P. gingivalis trypsin-like enzyme 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), KAS4 (SEQ ID NO: 64), KAS5 (SEQ ID NO: 65), KAS6 (SEQ ID NO: 66), RAS1 (SEQ ID NO: 31), KAS2 (SEQ ID NO: 32), RAS3 (SEQ ID NO: 33), RAS4 (SEQ ID NO: 67), RAS5 (SEQ ID NO: 68), and PAS1R (SEQ ID NO: 34); and at least one sequence that comprises an adhesin domain of P. gingivalis , or fragment thereof, selected from:

(i) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Lys-X-proteinase of P. gingivalis ; and

(ii) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Arg-X-proteinase of P. gingivalis ; and

(iii) part of, or all of a sequence that is the same as, or homologous to the sequence of a HagA adhesin domain of P. gingivalis.

89 . The chimeric or fusion protein according to claim 74 wherein said first peptide comprises a sequence that is the same as or homologous to the sequence set out in SEQ ID NO:28 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to the sequence shown in SEQ ID No: 37.

90 . The chimeric or fusion protein according to claim 74 wherein said first peptide comprises a sequence that is the same as or homologous to the sequence set out in SEQ ID NO:27 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to the sequence shown in SEQ ID No: 36.