Compositions and methods for the therapy and diagnosis of inflammatory bowel disease

• US 9,290,543 B2
• Filed: 02/25/2008
• Issued: 03/22/2016
• Est. Priority Date: 12/17/2001
• Status: Active Grant

• Current Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Original Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Inventors: Hershberg, Robert M., Hosken, Nancy Ann, Lodes, Michael J., Mohamath, Raodoh, Targan, Stephan R.
• Primary Examiner(s): Li, Ruixiang
• Application Number:
  US12/036,588
• Publication Number:
  US 20090142778A1
• Time in Patent Office: 2,948 Days
• Field of Search: None
• 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. A method for identifying an inflammatory bowel disease (IBD) type in a patient diagnosed with IBD, wherein the IBD type is Crohn'"'"'s disease (CD), the method comprising:

(a) contacting a serum sample obtained from the patient with a polypeptide comprising the full-length CBir1 flagellin sequence set forth in SEQ ID NO;

86 or a fragment thereof, wherein the polypeptide fragment comprises at least about 25, 50, 100, or more contiguous amino acids of the amino terminal conserved region (amino acid residues 1-147) of the sequence set forth in SEQ ID NO;

86, wherein the serum sample comprises antibodies that bind to the polypeptide or fragment thereof;

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

(c) comparing the amount of bound antibody to a predetermined cut-off value, wherein an amount of bound antibody higher than the predetermined cut-off value indicates that the IBD type is CD, thereby identifying the IBD type in the patient.

2. The method of claim 1, wherein the patient is a human.

3. The method of claim 1, wherein the polypeptide fragment consists of the amino terminal conserved region (amino acid residues 1-147) of the sequence set forth in SEQ ID NO:

86.

4. The method of claim 1, wherein the polypeptide fragment consists of the amino terminal conserved region plus the variable region (amino acid residues 1-418) of the sequence set forth in SEQ ID NO:

86.

5. The method of claim 1, wherein the polypeptide fragment further comprises a six histidine (SEQ ID NO:

90) tag.

6. The method of claim 1, wherein the polypeptide fragment consists of the amino terminal conserved region (amino acid residues 1-147) of the sequence set forth in SEQ ID NO:

86 and a six histidine (SEQ ID NO;

90) tag.

7. The method of claim 1, wherein the polypeptide fragment consists of the amino terminal conserved region plus the variable region (amino acid residues 1-418) of the sequence set forth in SEQ ID NO:

86 and a six histidine (SEQ ID NO;

90) tag.

8. The method of claim 1, wherein the polypeptide or fragment thereof is immobilized on a solid support.

9. The method of claim 1, wherein the amount of bound antibody is detected using a detection reagent comprising a reporter group.

10. The method of claim 9, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A, or a lectin.

11. The method of claim 9, wherein the reporter group is selected from the group consisting of radioactive groups, fluorescent groups, luminescent groups, enzymes, biotin, and dyes.

12. The method of claim 1, wherein the predetermined cut-off value is a level of antibody in a serum sample of a patient with ulcerative colitis (UC) that binds to the polypeptide or fragment thereof.