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

• US 20160362481A1
• Filed: 02/18/2016
• Published: 12/15/2016
• Est. Priority Date: 12/17/2001
• Status: Active Grant

• Current Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Original Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Inventors: Hershberg, Robert, Hosken, Nancy Ann, Lodes, Michael J., Mohamath, Raodoh, Targan, Stephan R.
• Granted Patent: US 9,868,779 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 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

1-5. -5. (canceled)

6. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide comprising a sequence that is at least 70% identical to any of SEQ ID NOs:

79, 84, 86, 80-82, 38-50, or 88-89.

7. The antibody according to claim 6 wherein said antibody is a monoclonal antibody.

8. The antibody according to claim 6 wherein said antibody is a human antibody.

9. The antibody according to claim 6 wherein said antibody is a humanized antibody.

10. The antibody according to claim 6 wherein said antibody binds to a flagellin protein.

11. The antibody according to claim 10 wherein said antibody is a neutralizing antibody against said flagellin protein.

12. The antibody according to claim 6 wherein said antibody blocks the interaction between a flagellin protein and a Toll-like receptor

73. The antibody according to claim 6 wherein the antibody specifically binds to a polypeptide comprising a sequence that is at least 90% identical to SEQ ID NO:

79.

74. The antibody according to claim 73 wherein the antibody specifically binds to a polypeptide having the sequence of SEQ ID NO:

79.

75. The antibody according to claim 6 wherein the antibody specifically binds to a polypeptide comprising a sequence that is at least 90% identical to SEQ ID NO:

86.

76. The antibody according to claim 75 wherein the antibody specifically binds to a polypeptide having the sequence of SEQ ID NO:

86.

77. The antibody according to claim 6 further comprising a label.

78. The antibody according to claim 6 further comprising a therapeutic agent coupled to the antibody.

79. The antibody according to claim 78, wherein the therapeutic agent is a radionuclide, differentiation inducer, drug, or toxin.

80. A composition comprising the antibody according to claim 6 and a pharmaceutically acceptable carrier.

81. The composition according to claim 80, further comprising an immunostimulant.

82. The composition according to claim 81, wherein the immunostimulant is an adjuvant selected from the group consisting of Freund'"'"'s Incomplete Adjuvant, Freund'"'"'s Complete Adjuvant, Merck Adjuvant 65, AS-1, AS-2;

aluminum hydroxide gel;

aluminum phosphate;

a salt of calcium, iron or zinc;

an insoluble suspension of acylated tyrosine acylated sugars;

cationically or anionically derivatized polysaccharides;

polyphosphazenes;

biodegradable microspheres;

monophosphoryl lipid A, QS21, aminoalkyl glucosaminide 4-phosphates, and quil A.

83. A kit comprising the antibody according to claim 6 and a detection reagent, wherein the detection reagent comprises a reporter group.

84. The kit according to claim 83, wherein the detection agent comprises an anti-immunoglobulin, protein G, protein A, or a lectin.

85. The kit according to claim 83, wherein the reporter group is selected from the group consisting of radioactive groups, fluorescent groups, luminescent groups, enzymes, biotin, and dyes.

13-72. -72. (canceled)