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

• US 9,175,046 B2
• Filed: 11/21/2012
• Issued: 11/03/2015
• Est. Priority Date: 12/17/2001
• Status: Expired due to Fees

• Current Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Original Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Inventors: Hershberg, Robert, Hosken, Nancy Ann, Lodes, Michael J., Mohamath, Raodoh
• Primary Examiner(s): Li, Ruixiang
• Application Number:
  US13/684,077
• Publication Number:
  US 20130231293A1
• Time in Patent Office: 1,077 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 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. An isolated polypeptide comprising an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO:

79, wherein the isolated polypeptide is immunologically reactive to sera from a patient with inflammatory bowel disease (IBD), and said sera comprise an anti-flagellin antibody.

2. The isolated polypeptide of claim 1, 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.

3. The isolated polypeptide of claim 1, wherein the polypeptide comprises an amino acid sequence having at least 95% identity to the sequence set forth in SEQ ID NO:

79.

4. The isolated polypeptide of claim 1, 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.

5. The isolated polypeptide of claim 1, wherein the polypeptide is immobilized on a solid support.

6. A fusion protein comprising a polypeptide according to claim 1.

7. A composition comprising a physiologically acceptable carrier and a polypeptide according to claim 1.

8. An isolated polypeptide fragment consisting of at least 25, 50, 100, or all contiguous amino acids of the sequence of SEQ ID NO:

79, wherein the polypeptide fragment is immunologically reactive to sera from a patient with inflammatory bowel disease (IBD), and said sera comprise an anti-flagellin antibody.

9. A fusion protein comprising a polypeptide fragment according to claim 8.

10. A fusion protein consisting of a polypeptide fragment according to claim 8 and a six histidine (SEQ ID NO:

90) tag.

11. The isolated polypeptide fragment of claim 8 wherein the at least 25, 50, or 100 contiguous amino acids of the sequence of SEQ ID NO:

79 are;

(a) at least 25, 50, or 100 contiguous amino acids of the amino acid 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) at least 25, 50, or 100 contiguous amino acids of the amino acid 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.

12. A fusion protein comprising a polypeptide fragment according to claim 11.

13. The isolated polypeptide fragment of claim 11, wherein the polypeptide fragment comprises the sequence set forth in SEQ ID NO:

80.

14. The isolated polypeptide fragment of claim 11, wherein the polypeptide fragment comprises the sequence set forth in SEQ ID NO:

81.

15. A fusion protein consisting of a polypeptide fragment according to claim 11 and a six histidine (SEQ ID NO 90) tag.

16. A kit comprising:

(a) at least one polypeptide fragment of claim 8; and

(b) a detection reagent comprising a reporter group.

17. The kit of claim 16, wherein said at least one polypeptide fragment is immobilized on a solid support.

18. The kit of claim 16, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A, or a lectin.

19. The kit of claim 16, wherein the reporter group is selected from the group consisting of radioactive groups, fluorescent groups, luminescent groups, enzymes, biotin, and dyes.