COMPOSITIONS AND METHODS FOR THE THERAPY AND DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE

• US 20120039924A1
• Filed: 04/22/2011
• Published: 02/16/2012
• Est. Priority Date: 12/17/2001
• Status: Active Grant

• Current Assignee: Corixa Corporation (GSK plc)
• Original Assignee: Corixa Corporation (GSK plc)
• Inventors: Hershberg, Robert M., Hosken, Nancy Ann, Lodes, Michael J., Mohamath, Raodoh
• Granted Patent: US 8,318,901 B2
• Time in Patent Office: Days
• US Class Current: 424/190.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/523 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/40 bacterial
• CPC Class Codes: A61K 39/46 Cellular immunotherapy
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4648 Bacterial antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 14/195 from bacteria
• CPC Class Codes: C07K 14/205 from Campylobacter (G)
• CPC Class Codes: C07K 16/1232 from Escherichia (G)
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: G01N 2800/065 : Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
• CPC Class Codes: G01N 33/505 : involving T-cells
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere

Abstract

Compositions and methods for the therapy and diagnosis of Inflammatory Bowel Disease (IBD), including Crohn'"'"'s Disease and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of IBD.

Claims

1-72. -72. (canceled)

73. An isolated polypeptide comprising an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO:

79.

74. The isolated polypeptide of claim 73, wherein the polypeptide comprises an amino acid sequence having at least 91%, 92%, 93%, or 94% identity to the sequence set forth in SEQ ID NO:

79.

75. The isolated polypeptide of claim 73, wherein the polypeptide comprises an amino acid sequence having at least 95% identity to the sequence set forth in SEQ ID NO:

79.

76. The isolated polypeptide of claim 73, wherein the polypeptide comprises an amino acid sequence having at least 96%, 97%, 98%, or 99% identity to the sequence set forth in SEQ ID NO:

79.

77. The isolated polypeptide of claim 73, wherein the polypeptide comprises the sequence set forth in SEQ ID NO:

79.

78. The isolated polypeptide of claim 73, wherein the polypeptide is immobilized on a solid support.

79. A fusion protein comprising a polypeptide according to claim 73.

80. A composition comprising a physiologically acceptable carrier and a polypeptide according to claim 73.

94. A method of detecting the presence of inflammatory bowel disease in a mammal, comprising the steps of:

(a) contacting a biological sample obtained from a mammal comprising antibodies with a polypeptide of claim 73;

(b) detecting in the sample an amount of antibody that binds to the polypeptide; and

(c) comparing the amount of bound antibody to a predetermined cut-off value and therefrom determining the presence of inflammatory bowel disease in the mammal.

96. A method of monitoring the progression of inflammatory bowel disease in a mammal, comprising the steps of:

(a) contacting a biological sample obtained from a mammal comprising antibodies with a polypeptide of claim 73;

(b) detecting in the sample an amount of antibody that binds to the polypeptide; and

(c) repeating steps (a) and (b) using a biological sample obtained from the mammal at a subsequent point in time; and

(d) comparing the amount of bound antibody in step (b) to the amount of bound antibody in step (c) and therefrom monitoring the progression of inflammatory bowel disease in the mammal.

81. An isolated polypeptide fragment comprising at least about 25, 50, 100 or more contiguous amino acids of the sequence of SEQ ID NO:

79, wherein the polypeptide fragment is immunologically reactive with an antibody that binds to the full-length polypeptide of SEQ ID NO;

79.

82. A fusion protein comprising a polypeptide fragment according to claim 81.

83. A fusion protein consisting of a polypeptide fragment according to claim 81 and a six histidine (SEQ ID NO:

90) tag.

84. The polypeptide fragment of claim 81, wherein the polypeptide fragment comprises:

(a) an amino acid sequence having at least 95% identity to the sequence set forth in SEQ ID NO;

80, which corresponds to the amino terminal conserved region of the sequence set forth in SEQ ID NO;

79;

or

(b) an amino acid sequence having at least 95% identity to the sequence set forth in SEQ ID NO;

81, which corresponds to the amino terminal conserved region plus the variable region of the sequence set forth in SEQ ID NO;

79.

85. A fusion protein comprising a polypeptide fragment according to claim 84.

86. The isolated polypeptide fragment of claim 84, wherein the polypeptide fragment comprises the sequence set forth in SEQ ID NO:

80.

87. The isolated polypeptide fragment of claim 84, wherein the polypeptide fragment comprises the sequence set forth in SEQ ID NO:

81.

88. A fusion protein consisting of a polypeptide fragment according to claim 84 and a six histidine (SEQ ID NO 90) tag.

89. A kit comprising:

(a) at least one polypeptide fragment of claim 81; and

(b) a detection reagent comprising a reporter group.

90. The kit of claim 89, wherein said at least one polypeptide fragment is immobilized on a solid support.

91. The kit of claim 89, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A, or a lectin.

92. The kit of claim 89, wherein the reporter group is selected from the group consisting of radioactive groups, fluorescent groups, luminescent groups, enzymes, biotin, and dyes.

93. An isolated polynucleotide comprising a sequence selected from the group consisting of:

(a) the sequence provided in SEQ ID NO 75;

(b) the complement of the sequence provided in SEQ ID NO 75;

(c) sequences having at least 75% identity to the sequence of SEQ ID NO 75; and

(d) sequences having at least 90% identity to the sequence of SEQ ID NO 75.

95. A method of detecting the presence of inflammatory bowel disease in a mammal, comprising the steps of:

(a) contacting a biological sample obtained from a mammal comprising polynucleotides with at least one oligonucleotide that is at least in part complementary to a polynucleotide of claim 93;

(b) detecting in the sample an amount of a polynucleotide that hybridizes to said oligonucleotide; and

(c) comparing the amount of said polynucleotide that hybridizes to said oligonucleotide to a predetermined cut-off value, and therefrom determining the presence of inflammatory bowel disease in a mammal.

97. A method of monitoring the progression of inflammatory bowel disease in a mammal, comprising the steps of:

(a) contacting a biological sample obtained from a mammal comprising polynucleotides with at least one oligonucleotide that is at least in part complementary to a polynucleotide of claim 93;

(b) detecting in the sample an amount of a polynucleotide that hybridizes to said oligonucleotide;

(c) repeating steps (a) and (b) using a biological sample obtained from said mammal at a subsequent point in time; and

(d) comparing the amount of said polynucleotide that hybridizes to said oligonucleotide in step (b) to the amount of said polynucleotide that hybridizes to said oligonucleotide in step (c);

and therefrom monitoring the progression of inflammatory bowel disease in a mammal.