Compositions and methods for the treatment of immune related diseases

• US 20030054484A1
• Filed: 08/05/2002
• Published: 03/20/2003
• Est. Priority Date: 04/20/1999
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Gurney, Austin L., Goddard, Audrey, Wood, William I., Zhang, Zemin, Grimaldi, J. Christopher, Tumas, Daniel, Fong, Sherman, Hillan, Kenneth J., Godowski, Paul J., Watanabe, Colin K.
• Granted Patent: US 7,282,570 B2
• Time in Patent Office: Days
• US Class Current: 435/69.1
• 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: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 5/06 Animal cells or tissues; Human cells or tissues preservation of living cells or tissues A01N1/02
• CPC Class Codes: C12N 9/00 Enzymes; Proenzymes; Compositions thereof preparations containing enzymes for cleaning teeth A61K8/66, A61Q11/00; medicinal preparations containing enzymes or proenzymes A61K38/43; enzyme containing detergent compositions C11D; enzymes with nucleic acid structure, e.g. ribozymes, C12N15/113; Processes for preparing, activating, inhibiting, separating or purifying enzymes preparation of malt C12C1/00
• CPC Class Codes: C12P 21/02 having a known sequence of two or more amino acids, e.g. glutathione
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to compositions containing novel proteins and methods of using those compositions for the diagnosis and treatment of immune related diseases.

Claims

1. Isolated nucleic acid having at least 80% nucleic acid sequence identity to:

(a) a nucleotide sequence encoding the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18).

(b) a nucleotide sequence encoding the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18), lacking its associated signal peptide;

(c) a nucleotide sequence encoding an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18), with its associated signal peptide;

or

(d) a nucleotide sequence encoding an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18) lacking its associated signal peptide.

5. A vector comprising the nucleic acid of claim 1.

6. The vector of claim 5 operably linked to control sequences recognized by a host cell transformed with the vector.

7. A host cell comprising the vector of claim 5.

8. The host cell of claim 7, wherein said cell is a CHO cell, an E. coli cell or a yeast cell.

9. A process for producing a PRO polypeptide comprising culturing the host cell of claim 7 under conditions suitable for expression of said PRO polypeptide and recovering said PRO polypeptide from the cell culture.

2. Isolated nucleic acid having at least 80% nucleic acid sequence identity to a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:

1), FIG. 3 (SEQ ID NO;

3), FIG. 5 (SEQ ID NO;

5), FIG. 7 (SEQ ID NO;

7), FIG. 9 (SEQ ID NO;

9), FIG. 11 (SEQ ID NO;

11), FIG. 13 (SEQ ID NO;

13), FIG. 15 (SEQ ID NO;

15) and FIG. 17 (SEQ ID NO;

17).

3. Isolated nucleic acid having at least 80% nucleic acid sequence identity to a nucleotide sequence selected from the group consisting of the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:

1), FIG. 3 (SEQ ID NO;

3), FIG. 5 (SEQ ID NO;

5), FIG. 7 (SEQ ID NO;

7), FIG. 9 (SEQ ID NO;

9), FIG. 11 (SEQ ID NO;

11), FIG. 13 (SEQ ID NO;

13), FIG. 15 (SEQ ID NO;

15) and FIG. 17 (SEQ ID NO;

17).

4. Isolated nucleic acid having at least 80% nucleic acid sequence identity to the full-length coding sequence of the DNA deposited under any ATCC accession number shown in Table 7.

10. An isolated polypeptide having at least 80% amino acid sequence identity to:

(a) an amino acid sequence of the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18);

(b) an amino acid sequence of the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18), lacking its associated signal peptide;

(c) an amino acid sequence of an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18), with its associated signal peptide;

or

(d) an amino acid sequence of an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

2), FIG. 4 (SEQ ID NO;

4), FIG. 6 (SEQ ID NO;

6), FIG. 8 (SEQ ID NO;

8), FIG. 10 (SEQ ID NO;

10), FIG. 12 (SEQ ID NO;

12), FIG. 14 (SEQ ID NO;

14), FIG. 16 (SEQ ID NO;

16) or FIG. 18 (SEQ ID NO;

18), lacking its associated signal peptide.

12. A chimeric molecule comprising a polypeptide according to claim 10 fused to a heterologous amino acid sequence.

13. The chimeric molecule of claim 12, wherein said heterologous amino acid sequence is an epitope tag sequence or an Fe region of an immunoglobulin.

14. An antibody which specifically binds to a polypeptide according to claim 10.

15. The antibody of claim 14, wherein said antibody is a monoclonal antibody, a humanized antibody or a single-chain antibody.

16. A composition of matter comprising (a) a polypeptide of claim 10, (b) an agonist of said polypeptide, (c) an antagonist of said polypeptide, or (d) an antibody that binds to said polypeptide, in combination with a carrier.

17. The composition of matter of claim 16, wherein said carrier is a pharmaceutically acceptable carrier.

18. The composition of matter of claim 16 which is useful for the treatment of an immune related disease in a mammal.

19. The composition of matter of claim 16, wherein (a), (b), (c) or (d) is capable of (i) enhancing the proliferation of T-lymphocytes in a mammal, (ii) inhibiting the proliferation of T-lymphocytes in a mammal, or (iii) increasing infiltration of inflammatory cells into a tissue of a mammal.

20. The composition of matter of claim 16 comprising a therapeutically effective amount of (a), (b), (c) or (d).

21. An article of manufacture, comprising:

a container;

a label on said container; and

a composition of matter comprising (a) a polypeptide of claim 10, (b) an agonist of said polypeptide, (c) an antagonist of said polypeptide, or (d) an antibody that binds to said polypeptide, contained within said container, wherein label on said container indicates that said composition of matter can be used for treating an immune related disease.

22. A method of treating an immune related disorder in a mammal in need thereof comprising administering to said mammal a therapeutically effective amount of (a) a polypeptide of claim 10, (b) an agonist of said polypeptide, (c) an antagonist of said polypeptide, or (d) an antibody that binds to said polypeptide.

23. The method of claim 22, wherein the immune related disorder is systemic lupus erythematosis, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, a spondyloarthropathy, systemic sclerosis, an idiopathic inflammatory myopathy, Sjö

gren'"'"'s syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune-mediated renal disease, a demyelinating disease of the central or peripheral nervous system, idiopathic demyelinating polyneuropathy, Guillain-Barré

syndrome, a chronic inflammatory demyelinating polyneuropathy, a hepatobiliary disease, infectious or autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, sclerosing cholangitis, inflammatory bowel disease, gluten-sensitive enteropathy, Whipple'"'"'s disease, an autoimmune or immune-mediated skin disease, a bullous skin disease, erythema multiforme, contact dermatitis, psoriasis, an allergic disease, asthma, allergic rhinitis, atopic dermatitis, food hypersensitivity, urticaria, an immunologic disease of the lung, eosinophilic pneumonias, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, a transplantation associated disease, graft rejection or graft-versus-host-disease.

11. An isolated polypeptide having at least 80% amino acid sequence identity to an amino acid sequence encoded by the full-length coding sequence of the DNA deposited under any ATCC accession number shown in Table 7.

24. A method for determining the presence of a PRO1081, PRO1274, PRO1199, PRO1754, PRO1556, PRO4401, PRO9912, PRO10268 or PRO10272 polypeptide in a sample suspected of containing said polypeptide, said method comprising exposing said sample to an anti-PRO1081, anti-PRO1274, anti-PRO1199, anti-PRO1754, anti-PRO1556, anti-PRO4401, anti-PRO9912, anti-PRO10268 or anti-PRO10272 antibody and determining binding of said antibody to a component of said sample.

25. A method of diagnosing an immune related disease in a mammal, said method comprising detecting the level of expression of a gene encoding PRO1081, PRO1274, PRO1199, PRO1754, PRO1556, PRO4401, PRO9912, PRO10268 or PRO10272 polypeptide (a) in a test sample of tissue cells obtained from the mammal, and (b) in a control sample of known normal tissue cells of the same cell type, wherein a higher or lower level of expression of said gene in the test sample as compared to the control sample is indicative of the presence of an immune related disease in the mammal from which the test tissue cells were obtained.

26. A method of diagnosing an immune related disease in a mammal, said method comprising (a) contacting an an anti-PRO1081, anti-PRO1274, anti-PRO1199, anti-PRO1754, anti-PRO1556, anti-PRO4401, anti-PRO9912, anti-PRO10268 or anti-PRO10272 antibody with a test sample of tissue cells obtained from said mammal and (b) detecting the formation of a complex between the antibody and the polypeptide in the test sample, wherein formation of said complex is indicative of the presence of an immune related disease in the mammal from which the test tissue cells were obtained.

27. A method of identifying a compound that inhibits the activity of a PRO1081, PRO1274, PRO1199, PRO1754, PRO1556, PRO4401, PRO9912, PRO10268 or PRO10272 polypeptide, said method comprising contacting cells which normally respond to said polypeptide with (a) said polypeptide and (b) a candidate compound, and determining the lack responsiveness by said cell to (a).

28. A method of identifying a compound that inhibits the expression of a gene encoding a PRO1081, PRO1274, PRO1199, PRO1754, PRO1556, PRO4401, PRO9912, PRO10268 or PRO10272 polypeptide, said method comprising contacting cells which normally express said polypeptide with a candidate compound, and determining the lack of expression said gene.

29. The method of claim 28, wherein said candidate compound is an antisense nucleic acid.

30. A method of identifying a compound that mimics the activity of a PRO1081, PRO1274, PRO1199, PRO1754, PRO1556, PRO4401, PRO9912, PRO10268 or PRO10272 polypeptide, said method comprising contacting cells which normally respond to said polypeptide with a candidate compound, and determining the responsiveness by said cell to said candidate compound.

31. A method of stimulating the proliferation of T-lymphocytes, said method comprising contacting T-lymphocytes with an effective amount of (a) a PRO1081, PRO1274 or PRO10272 polypeptide or (b) an agonist of (a), wherein the proliferation of said T-lymphocytes is stimulated.

32. A method of inhibiting the proliferation of T-lymphocytes, said method comprising contacting T-lymphocytes with an effective amount of an antagonist of a PRO1081, PRO1274 or PRO10272 polypeptide, wherein the proliferation of said T-lymphocytes is inhibited.

33. A method of inhibiting the proliferation of T-lymphocytes, said method comprising contacting T-lymphocytes with an effective amount of (a) a PRO1199, PRO1556, PRO4401 or PRO10268 polypeptide or (b) an agonist of (a), wherein the proliferation of said T-lymphocytes is inhibited.

34. A method of stimulating the proliferation of T-lymphocytes, said method comprising contacting T-lymphocytes with an effective amount of an antagonist of a PRO199, PRO1556, PRO4401 or PRO10268 polypeptide, wherein the proliferation of said T-lymphocytes is stimulated.

35. A method of enhancing the infiltration of inflammatory cells into a tissue of a mammal, said method comprising administering to said tissue an effective amount of (a) a PRO1754 or PRO9912 polypeptide or (b) an agonist of (a), wherein said infiltration is enhanced.

36. The method of claim 35, wherein said inflammatory cells are mononuclear cells, cosinophils or polymorphonuclear neutrophils (PMNs).