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

• US 7,361,733 B2
• Filed: 05/30/2003
• Issued: 04/22/2008
• Est. Priority Date: 12/17/2001
• Status: Active Grant

• Current Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Original Assignee: Corixa Corporation (GlaxoSmithKline PLC)
• Inventors: Lodes, Michael J., Hershberg, Robert M., Mohamath, Raodoh, Hosken, Nancy Ann
• Primary Examiner(s): Li; Ruixiang
• Application Number:
  US10/449,857
• Publication Number:
  US 20040043931A1
• Time in Patent Office: 1,789 Days
• Field of Search: None
• US Class Current: 530/350
• 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. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

86.

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

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

4. The composition of claim 3, further comprising an immunostimulant.

5. The composition of claim 4, wherein said 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.

16. A composition comprising a physiologically acceptable carrier and a fusion protein according to claim 2.

6. A kit comprising:

(a) at least one polypeptide fragment of SEQ ID NO;

86, wherein said fragment comprises amino acid residues 1-147 of the full-length Cbir-1 flagellin sequence set forth in SEQ ID NO;

86; and

(b) a detection reagent comprising a reporter group.

7. A kit according to claim 6, wherein said at least one polypeptide fragment is immobilized on a solid support.

8. A kit according to claim 6, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A, or a lectin.

9. A kit according to claim 6, wherein the reporter group is selected from the group consisting of radioactive groups, fluorescent groups, luminescent groups, enzymes, biotin, and dyes.

10. An isolated polypeptide fragment consisting of at least about 25, 50, 100, or more contiguous amino acids of the full-length Cbir-1 flagellin sequence set forth in SEQ ID NO:

86, wherein the polypeptide fragment is immunologically reactive with an antibody that binds to the full-length Cbir-1 flagellin sequence.

11. The isolated polypeptide fragment of claim 10, wherein the polypeptide fragment is the amino terminal conserved region (amino acid residues 1-147) of the sequence set forth in SEQ ID NO:

86.

12. The isolated polypeptide fragment of claim 10, wherein the polypeptide fragment is the amino terminal conserved region plus the variable region (amino acid residues 1-418) of the sequence set forth in SEQ ID NO:

86.

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

90) tag.

14. A fusion protein consisting of a polypeptide fragment according to claim 11 and a six histidine (SEQ ID NO:

90) tag.

15. A fusion protein consisting of a polypeptide fragment according to claim 12 and a six histidine (SEQ ID NO:

90) tag.