Diagnostic Methods

• US 20090075299A1
• Filed: 09/12/2008
• Published: 03/19/2009
• Est. Priority Date: 09/14/2007
• Status: Active Grant

• Current Assignee: Meso Scale Technologies, LLC
• Original Assignee: Meso Scale Technologies, LLC
• Inventors: Glezer, Eli, Stengelin, Martin, Mathew, Anu
• Granted Patent: US 8,053,198 B2
• Time in Patent Office: Days
• US Class Current: 435/7.400
• CPC Class Codes: G01N 2333/475 Assays involving growth factors
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2333/91215 with a definite EC number (2.7.1.-)
• CPC Class Codes: G01N 2333/96419 Metalloendopeptidases (3.4.24)
• CPC Class Codes: G01N 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/57442 of the uterus and endometrial
• CPC Class Codes: G01N 33/57449 of ovaries

Abstract

The present invention relates to methods of diagnosing cancerous conditions in a patient, as well as methods of monitoring the progression of a cancerous condition and/or methods of monitoring a treatment protocol of a therapeutic agent or a chemotherapeutic regimen. The invention also relates to assay methods used in connection with the diagnostic methods described herein.

Claims

1. A method for diagnosing a cancerous condition in a patient comprising

(a) measuring a level of a first biomarker in a test sample obtained from a patient, wherein said first biomarker is selected from the group consisting of Flt-1, MMP-10, PIGF, and combinations thereof,

(b) diagnosing from said measuring step the presence or absence of said cancerous condition in said patient.

2. The method of claim 1 wherein said method further comprises measuring a level of at least one additional biomarker in said sample and determining from said level of said first biomarker and said level of said at least one additional biomarker the presence or absence of said cancerous condition in said patient.

3. The method of claim 1 wherein said method further comprises comparing said level of said first biomarker in said sample to a level of said first biomarker in a normal control sample and diagnosing the presence or absence of said cancerous condition in said patient based on said comparison.

4. The method of claim 2 wherein said method further comprises comparing said level of said first biomarker and said at least one additional biomarker(s) in said sample to a level of said first biomarker and said at least one additional biomarker(s) in a normal control sample and diagnosing the presence or absence of said cancerous condition in said patient based on said comparison.

5. The method of claim 2 wherein said at least one additional biomarker is selected from the group consisting of CA125, IL-6, CRP, SM, IL-8, IL-1β

, IL-2, P-Cadherin, Eotaxin-3, TNFR1, OPN, Prolactin, and combinations thereof.

6. The method of claim 1 wherein said cancerous condition is selected from the group consisting of ovarian, breast, endometrial cancers, and combinations thereof.

7. The method claim 1 wherein said patient is a premenopausal woman or a postmenopausal woman.

8. The method of claim 1, wherein said diagnosing step comprises comparing said level of said first biomarker to a detection cut-off level, wherein said first biomarker level above said detection cut-off level is indicative of said cancerous condition.

9. The method of claim 1, wherein said diagnosing step comprises comparing said level of said at least one additional biomarker to a detection cut-off level, wherein said at least one additional biomarker level above said detection cut-off level is indicative of said cancerous condition.

10. The method of claim 1 further comprising determining from said level of said first biomarker the disease progression of said cancerous condition.

29. The method of claim 1, wherein said measuring step is conducted on a single sample.

30. The method of claim 1, wherein said measuring step is conducted in a single assay chamber.

31. The method of claim 1, wherein said assay chamber is a single well of an assay plate.

32. The method of claim 1, wherein said assay chamber is an assay chamber of a cartridge.

33. The method of claim 1, wherein said sample is selected from the group consisting of blood, serum and plasma.

34. The method of claim 1, wherein said sample is selected from a group consisting of biopsy tissue, intestinal mucosa and urine.

35. The method of claim 1, wherein said level is measured using an immunoassay.

36. The method of claim 1 further comprising determining from said level of said first biomarker the disease progression of said cancerous condition.

37. The method of claim 1 wherein said first biomarker is Fit-1.

38. The method of claim 1 wherein said first biomarker is MMP-10.

39. The method of claim 1 wherein said first biomarker is PIGF.

40. The method of claim 1 wherein the sample is serum.

11. A method for monitoring the progression of a cancerous condition in a patient, said method comprising

(a) measuring the level(s) of a first biomarker in samples obtained, at different times, from said patient, wherein said first biomarker is selected from the group consisting of Flt-1, MMP-10, PIGF, and combinations thereof;

and

(b) determining from said level(s) of said first biomarker the progression or efficacy of treatment of said cancerous condition.

12. The method of claim 11 wherein said method further comprises measuring a level of at least one additional biomarker in said sample and determining from said level of said first biomarker and said level of said at least one additional biomarker the progression of said cancerous condition in said patient.

13. The method of claim 11 wherein said method further comprises comparing said level of said first biomarker in said sample to a level of said first biomarker in a normal control sample and determining the progression of said cancerous condition in said patient based on said comparison.

14. The method of claim 12 wherein said method further comprises comparing said level of said first biomarker and said at least one additional biomarker(s) in said sample to a level of said first biomarker and said at least one additional biomarker(s) in a normal control sample and determining the progression of said cancerous condition in said patient based on said comparison.

15. The method of claim 12 wherein said at least one additional biomarker is selected from the group consisting of CA125, IL-6, CRP, SAA, IL-8, IL-1β

, IL-2, P-Cadherin, Eotaxin-3, TNFR1, OPN, Prolactin, and combinations thereof.

16. The method of claim 11 wherein said cancerous condition is selected from the group consisting of ovarian, breast, endometrial cancers, and combinations thereof.

17. The method of claim 11 wherein said patient is a premenopausal woman or a postmenopausal woman.

18. The method of claim 11, wherein said determining step comprises comparing said level of said first biomarker to a detection cut-off level, wherein said first biomarker level above said detection cut-off level is indicative of said cancerous condition.

19. The method of claim 12, wherein said determining step comprises comparing said level of said at least one additional biomarker to a detection cut-off level, wherein said at least one additional biomarker level above said detection cut-off level is indicative of said cancerous condition.

20. A method for evaluating the efficacy of a cancer therapeutic agent or treatment regimen in a patient that has or is suspected to have a cancerous condition, said method comprising

(a) measuring the level of a first biomarker in a sample obtained from said patient, wherein said first biomarker is selected from the group consisting of Flt-1, MMP10, PIGF, and combinations thereof;

(b) measuring the level of said first biomarker in a sample of a tumor model that has been exposed to said agent or treatment regimen; and

(c) comparing the levels measured in steps (a) and (b) to determine the efficacy of said agent or treatment regimen.

21. The method of claim 20 wherein said method further comprises measuring a level of at least one additional biomarker in said sample and determining from said level of said first biomarker and said level of said at least one additional biomarker the progression of said cancerous condition in said patient.

22. The method of claim 20 wherein said method further comprises comparing said level of said first biomarker in said sample to a level of said first biomarker in a normal control sample and determining the progression of said cancerous condition in said patient based on said comparison.

23. The method of claim 21 wherein said method further comprises comparing said level of said first biomarker and said at least one additional biomarker(s) in said sample to a level of said first biomarker and said at least one additional biomarker(s) in a normal control sample and determining the progression of said cancerous condition in said patient based on said comparison.

24. The method of claim 21 wherein said at least one additional biomarker is selected from the group consisting of CA125, IL-6, CRP, SM, IL-8, IL-1β

, IL-2, P-Cadherin, Eotaxin-3, TNFR1, OPN, Prolactin, and combinations thereof.

25. The method of claim 20 wherein said cancerous condition is selected from the group consisting of ovarian, breast, endometrial cancers, and combinations thereof.

26. The method of claim 20 wherein said patient is a premenopausal woman or a postmenopausal woman.

27. The method of claim 20, wherein said determining step comprises comparing said level of said first biomarker to a detection cut-off level, wherein said first biomarker level above said detection cut-off level is indicative of said cancerous condition.

28. The method of claim 21, wherein said determining step comprises comparing said level of said at least one additional biomarker to a detection cut-off level, wherein said at least one additional biomarker level above said detection cut-off level is indicative of said cancerous condition.