Specific markers for pancreatic cancer
(19)AUSTRALIAN PATENT OFFICE (54) Title Specific markers for pancreatic cancer (51)6 International Patent Classification(s) G01N 033/68 G01N 033/574 (21) Application No: 2003294828 (22) Application Date: 2003.12.11 (87) WIPO No: WO04/055519 (30) Priority Data (31) Number (32) Date (33) Country 02028058.2 2002.12.17 EP 03025237.3 2003.11.05 EP (43) Publication Date : 2004 .07.09 (43) Publication Journal Date : 2004 .08.19 (71) Applicant(s) Sinogenomax Co. Ltd.; SINOGENOMAXCO. LTD. CHINESE NATIONAL HUMAN GENOMECENTER (72) Inventor(s) Chen, Jie; Hu, Liping; Liu, Tonq Hua;Lu, Zhao Hui; Shen, Yan(-1-1) Application NoAU2003294828 A8(19)AUSTRALIAN PATENT OFFICE (54) Title Specific markers for pancreatic cancer (51)6 International Patent Classification(s) G01N 033/68 G01N 033/574 (21) Application No: 2003294828 (22) Application Date: 2003.12.11 (87) WIPO No: WO04/055519 (30) Priority Data (31) Number (32) Date (33) Country 02028058.2 2002.12.17 EP 03025237.3 2003.11.05 EP (43) Publication Date : 2004 .07.09 (43) Publication Journal Date : 2004 .08.19 (71) Applicant(s) Sinogenomax Co. Ltd.; SINOGENOMAXCO. LTD. CHINESE NATIONAL HUMAN GENOMECENTER (72) Inventor(s) Chen, Jie; Hu, Liping; Liu, Tonq Hua;Lu, Zhao Hui; Shen, Yan-1- The present invention provides polypeptides which are up- or down-regulated in pancreatic cancer and which can be used as markers for diagnosis of pancreatic cancer. The invention also provides an in vitro method for the diagnosis of pancreatic cancer and/or the susceptibility to pancreatic cancer comprising the steps of a) obtaining a biological sample; and b) detecting and/or measuring the increase of one or more polypeptides as disclosed herein. Furthermore, screening methods relating to inhibitors and antagonists of the specific polypeptides disclosed herein are provided. Claims 1. A marker for diagnosis of pancreatic cancer comprising at least one polypeptide selected from the group consisting of the polypeptides listed in tables 2 and 3.
2. The marker of claim 1 wherein the group from which at least one polypeptide is selected consists of the polypeptides listed in table 2.
3. A polypeptide selected from the group consisting of the polypeptides listed in tables 2 and 3, for use as a marker or as a component of a marker for diagnosis of pancreatic cancer and/or the susceptibility to pancreatic cancer.
4. An in vitro method for the diagnosis of pancreatic cancer and/or the susceptibility to pancreatic cancer comprising the steps of a) obtaining a biological sample; and b) detecting and/or measuring the increase of a marker of claims 1 or 2.
5. The in vitro method of claim 4, wherein the marker comprises at least two polypeptides.
6. The in vitro method of claims 4 or 5 wherein said biological sample is derived from the group consisting of serum, plasma, pancreatic juice and cells of pancreatic tissue.
7. An in vitro method for the diagnosis of pancreatic cancer and/or the susceptibility to pancreatic cancer comprising the steps of a) obtaining a biological sample; and b) detecting and/or measuring the increase of at least one nucleic acid coding for the marker of claims 1 or 2. <Desc/Clms Page number 38> 8. The in vitro method of claim 7, wherein said nucleic acid molecule is RNA or DNA.
9. The in vitro method of claim 8, wherein said DNA is a cDNA.
10. The in vitro method of any one of claims 7 to 9, wherein the expression levels of at least one of said nucleic acids in an individual suspected to suffer from pancreatic cancer and/or to be susceptible to pancreatic cancer is compared to the expression levels of the same nucleic acids in a healthy individual.
11. The in vitro method of any one of claims 4 to 6, wherein the expression level of said marker in an individual suspected to suffer from pancreatic cancer and/or to be susceptible to pancreatic cancer is compared to the expression levels of the same marker in a healthy individual.
12. The in vitro method of claim 11, wherein an increase of the expression levels of said marker is indicative of pancreatic cancer or the susceptibility to pancreatic cancer.
13. A screening method for identifying and/or obtaining a compound which interacts with a polypeptide listed in tables 2 and/or 3 whose expression is upregulated in pancreatic cancer, comprising the steps of a) contacting said polypeptide with a compound or a plurality of compounds under conditions which allow interaction of said compound with said polypeptide; and b) detecting the interaction between said compound or plurality of compounds with said polypeptide. <Desc/Clms Page number 39> 14. A screening method for identifying and/or obtaining a compound which is an inhibitor or an antagonist of a polypeptide listed in tables 2 and/or 3 whose expression is upregulated in pancreatic cancer, comprising the steps of a) contacting a said polypeptide with a compound identified and/or obtained by the screening method of claim 13 under conditions which allow interaction of said compound with said polypeptide; b) determining the activity of said polypeptide; c) determining the activity of said polypeptide expressed in the host as defined in (a), which has not been contacted with said compound; and d) quantitatively relating the activity as determined in (b) and (c), wherein a decreased activity determined in (b) in comparison to (c) is indicative for an inhibitor or antagonist.
15. A screening method for identifying and/or obtaining a compound which is an inhibitor of the expression of a polypeptide listed in tables 2 and/or 3 whose expression is upregulated in pancreatic cancer, comprising the steps of a) contacting a host which expresses said polypeptide with a compound, b) determining the expression level and/or activity of said polypeptide; c) determining the expression level and/or activity of said polypeptide in the host as defined in (a), which has not been contacted with said compound; and d) quantitatively relating the expression level of said polypeptide as determined in (b) and (c), wherein a decreased expression level determined in (b) in comparison to (c) is indicative for an inhibitor of the expression of said polypeptide.
16. A compound identified and/or obtained by the screening methods of any one of claims 13 to 15.
17. A pharmaceutical composition comprising the compound of claim 16. <Desc/Clms Page number 40> 18. A method for the preparation of the pharmaceutical composition of claim 17 comprising formulating the compound of claim 16 in a pharmaceutically acceptable carrier or diluent.
19. Use of a compound of claim 16 for the preparation of a medicament for the treatment or prevention of pancreatic cancer.
20. Use of a compound of claim 16 for the preparation of a diagnostic composition for diagnosing pancreatic cancer or a predisposition for pancreatic cancer.
21. The use of claim 19 or 20 wherein said compound comprises an antibody, an antibody-derivative, an antibody fragment, a peptide or an antisense construct.
22. Antibodies against the proteins listed in tables 2 and/or 3, or antigen-binding fragments thereof, for the use in an in vitro method for the diagnosis of pancreatic cancer.
23. A kit for the diagnosis of pancreatic cancer comprising one or more of the antibodies, or antigen-binding fragments thereof, of claim 22.
24. A kit for the diagnosis of pancreatic cancer comprising one or more of the nucleic acids coding for the marker of claims 1 or 2.
25. A kit for screening of compounds that activate or inhibit any of the polypeptides listed in tables 2 and/or 3, or stimulate or inhibit the expression of any of said polypeptides. <Desc/Clms Page number 41> 26. A marker for diagnosis of pancreatic cancer comprising at least one polypeptide selected from the group consisting of the polypeptides listed in table 6.
27. The marker of claim 26, wherein said at least one polypeptide does not include Seq ID No. s 25 and 50 to 55.
28. The marker according to any one of claims 26 to 27, additionally comprising at least one of the polypeptides listed in table 5.
29. An in vitro method for the diagnosis of pancreatic cancer and/or the susceptibility to pancreatic cancer comprising the steps of a) obtaining a biological sample; and b) detecting and/or measuring the increase of at least one of the polypeptides listed in table 6.
30. The in vitro method of claim 29, additionally comprising the step of detecting and/or measuring the decrease of at least one of the polypeptides listed in table 5.
31. The in vitro method of claims 29 or 30, wherein said at least one polypeptide does not include Seq ID No. s 25 and 50 to 55.
32. The in vitro method of any one of claims 29 to 31, wherein said biological sample is derived from the group consisting of serum, plasma, pancreatic juice and cells of pancreatic tissue.
33. An in vitro method for the diagnosis of pancreatic cancer and/or the susceptibility to pancreatic cancer comprising the steps of <Desc/Clms Page number 42> a) obtaining a biological sample; and b) detecting and/or measuring the increase of at least one nucleic acid coding for the marker of any one of claims 26 to 28.
34. The in vitro method of claim 33, wherein said nucleic acid molecule is RNA or DNA.
35. The in vitro method of claim 34, wherein said DNA is a cDNA.
36. The in vitro method of any one of claims 33 to 35, wherein the expression levels of at least one of said nucleic acids in an individual suspected to suffer from pancreatic cancer and/or to be susceptible to pancreatic cancer is compared to the expression levels of the same nucleic acids in a healthy individual.
37. The in vitro method of any one of claims 33 to 36, wherein the expression level of said marker in an individual suspected to suffer from pancreatic cancer and/or to be susceptible to pancreatic cancer is compared to the expression levels of the same marker in a healthy individual.
38. The in vitro method of claim 37, wherein an increase of the expression levels of said marker is indicative of pancreatic cancer or the susceptibility to pancreatic cancer.
39. A screening method for identifying and/or obtaining a compound which interacts with a polypeptide selected from the group consisting of the polypeptides listed in table 6 whose expression is upregulated in pancreatic cancer, comprising the steps of a) contacting said polypeptide with a compound or a plurality of compounds under conditions which allow interaction of said compound with said polypeptide; and <Desc/Clms Page number 43> b) detecting the interaction between said compound or plurality of compounds with said polypeptide.
40. A screening method for identifying and/or obtaining a compound which is an inhibitor or an antagonist of a polypeptide listed in table 6 whose expression is upregulated in pancreatic cancer, comprising the steps of a) contacting said polypeptide with a compound identified and/or obtained by the screening method of claim 39 under conditions which allow interaction of said compound with said polypeptide; b) determining the activity of said polypeptide; c) determining the activity of said polypeptide expressed in the host as defined in (a), which has not been contacted with said compound; and d) quantitatively relating the activity as determined in (b) and (c), wherein a decreased activity determined in (b) in comparison to (c) is indicative for an inhibitor or antagonist.
41. A screening method for identifying and/or obtaining a compound which is an inhibitor of the expression of a polypeptide selected from the group consisting of the polypeptides listed in table 6 whose expression is upregulated in pancreatic cancer, comprising the steps of a) contacting a host which expresses said polypeptide with a compound, b) determining the expression level and/or activity of said polypeptide; c) determining the expression level and/or activity of said polypeptide in the host as defined in (a), which has not been contacted with said compound; and d) quantitatively relating the expression level of said polypeptide as determined in (b) and (c), wherein a decreased expression level determined in (b) in comparison to (c) is indicative for an inhibitor of the expression of said polypeptide. <Desc/Clms Page number 44> 42. A compound identified and/or obtained by the screening methods of any one of claims 39 to 41.
43. A pharmaceutical composition comprising the compound of claim 42.
44. A method for the preparation of the pharmaceutical composition of claim 43 comprising formulating the compound of claim 42 in a pharmaceutically acceptable carrier or diluent.
45. Use of a compound of claim 42 for the preparation of a medicament for the treatment or prevention of pancreatic cancer.
46. Use of a compound of claim 42 for the preparation of a diagnostic composition for diagnosing pancreatic cancer or a predisposition for pancreatic cancer.
47. The use of claim 45 or 46 wherein said compound comprises an antibody, an antibody-derivative, an antibody fragment, a peptide or an antisense construct.
48. Antibodies against the proteins listed in tables 5 and/or 6, or antigen-binding fragments thereof, for the use in an in vitro method for the diagnosis of pancreatic cancer.
49. A kit for the diagnosis of pancreatic cancer comprising one or more of the antibodies, or antigen-binding fragments thereof, of claim 48.
50. A kit for the diagnosis of pancreatic cancer comprising one or more of the nucleic acids coding for the marker of claims 26 to 28. <Desc/Clms Page number 45> 51. A kit for screening of compounds that activate or inhibit any of the polypeptides listed in table 5 and/or 6, or stimulate or inhibit the expression of any of said polypeptides.
52. The kit of claim 51, wherein said polypeptides are the polypeptides listed in table 6.
53. The proteins, compounds, kits, methods and uses substantially as herein before described, especially with reference to the foregoing examples.