Diagnostic test for thrombotic or thromboembolic disease

• US 6,673,561 B1
• Filed: 06/30/2000
• Issued: 01/06/2004
• Est. Priority Date: 06/30/1999
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Morris, Timothy A.
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): GRUN, JAMES LESLIE
• Application Number:
  US09/609,275
• Time in Patent Office: 1,285 Days
• Field of Search: 435/7.1, 435/7.4, 435/7.92, 435/7.93, 435/7.94, 435/7.95, 435/13, 435/69.6, 435/70.21, 435/452, 435/331, 435/337, 435/975, 436/512, 436/501, 436/518, 436/524, 436/528-531, 436/534, 436/535, 436/538, 436/548, 436/172, 436/811, 436/514, 436/516, 530/387.3, 530/387.9, 530/388.25, 530/389.3, 530/391.1, 530/391.3
• US Class Current: 435/7.92
• CPC Class Codes: C07K 14/75 Fibrinogen
• CPC Class Codes: C07K 16/36 against blood coagulation factors
• CPC Class Codes: G01N 2333/75 Fibrin; Fibrinogen
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors
• CPC Class Codes: Y10S 436/811 Test for named disease, body condition or organ function

Abstract

Thrombotic or thromboembolic disease is detected or monitored by determining the presence or amount B in a urine sample.

Claims

1. A method for detecting thrombotic or thromboembolic diseases in a patient comprising detecting a presence or amount of Fibrinopeptide B (FPB) and/or des-arginine FPB peptides in a sample of urine from the patient to determine whether the patient has thrombotic or thromboembolic disease.

2. The method of claim 1, wherein detecting the presence or amount of FPB peptide comprises conducting an immunoassay for FPB peptides.

3. The method of claim 1, further comprising measuring an indicator of urine volume or rate of glomerular filtration.

4. The method of claim 1, further comprising determining if the FPB peptide in the sample is present at a concentration of greater than 50 ng/mL.

5. The method of claim 1, further comprising determining if the FPB peptide in the sample is present at a concentration significantly greater than in a normal population.

6. A method of monitoring treatment of thrombotic or thromboembolic diseases in a patient comprising measuring a Fibrinopeptide B (FPB) and/or des-arginine FPB peptides level in a sample of urine from the patient and determining the level is significantly greater than in a normal population to determine whether the patient has thrombotic or thromboembolic disease.

7. A method for monitoring treatment of thrombotic or thromboembolic disease caused by a thrombosis or embolism in a patient comprising:

(a) detecting an amount of Fibrinopeptide B (FPB) peptide present in a sample of urine obtained from the patient at a first time;

(b) detecting an amount of FPB peptide present in a second sample of urine obtained from the patient at a second later time; and

(c) comparing the amounts determined in steps (a) and (b) to determine whether the thrombosis or embolism is diminishing in size.

8. A diagnostic method for detecting thrombotic or thromboembolic disease in a patient comprising:

(a) contacting a urine sample from the patient, the sample suspected of containing a presence or amount of fibrinopeptide B (FPB) peptide and/or des-arginine FPB peptide, with an amount of detection agent specific for FPB and/or des-arginine FPB peptides to form an FPB;

detection agent complex; and

(b) detecting the presence or amount of FPB and/or des-arginine FPB peptides in the sample to determine whether the patient has thrombotic or thromboembolic disease.

10. The method of claim 8, wherein the detection agent is a monoclonal antibody.

11. The method of claim 8, wherein the detection agent is a polyclonal antibody.

14. The diagnostic method of claim 8 or 9, further comprising removing fibrinogen from the sample.

15. The diagnostic method of claim 8 or 9, wherein the thrombotic or thromboembolic disease is a deep venous thrombosis (DVT) or a pulmonary embolism (PE).

16. The method of claim 8 or 9, wherein a concentration of FPB and/or des-arginine FPB peptides in the sample above 50 ng/ml is reported as indicative of thrombotic or thromboembolic disease.

17. The method of claim 8 or 9, wherein a concentration of FPB and/or des-arginine FPB peptides in the sample above 100 ng/ml is reported as indicative of thrombotic or thromboembolic disease.

18. The method of claim 8 or 9, wherein the detection agent is an Fab, F(ab)₂, or Fv antibody fragment.

19. The method of claim 8 or 9, wherein the detection agent is attached to a substrate.

20. The method of claim 19, wherein the substrate is a gel, hydrogel, resin, bead, nitrocellulose, nylon filter, microtiter plate, culture flask, or polymeric material.

21. The method of claim 8 or 9, wherein the detection agent further comprises a detectable moiety.

22. The method of claim 21, wherein the detectable moiety is a radionuclide, enzyme, specific binding pair component, colloidal dye substance, fluorochrome, reducing substance, chemiluminescent substance, electrochemiluminescent substance, electroactive substance, latex, digoxigenin, metal, particulate, dansyl lysine, antibody, protein A, protein G, electron dense material, or chromophore.

23. The method according to claim 8 or 9, wherein the detection step (b) is by enzyme-linked immunosorbent assay, immunonephelometry, agglutination, precipitation, immunodiffusion, immunoelectrophoresis, immunofluorescence, electrochemiluminescence, surface plasmon resonance, chemiluminescence, electrochemical immunoassay, radioimmunoassay, or immunohistochemistry.

9. A diagnostic method for monitoring treatment of thrombotic or thromboembolic disease in a patient comprising:

(a) contacting a urine sample suspected of containing fibrinopeptide B (FFB) peptide and/or des-arginine FPB peptide with an amount of detection agent specific for FPB and/or des-arginine FPB peptides to form an FPB;

detection agent complex, wherein the sample is from a patient undergoing treatment for thrombotic or thromboembolic disease; and

(b) detecting a presence or amount of FPB and/or des-arginine FPB peptides in the sample to monitor changes in the presence or amount of FPB and/or des-arginine FPB peptides in the patient to monitor treatment of the patient for thrombotic or thromboembolic disease.

12. The method of claim 9, wherein the detection agent is a monoclonal antibody.

13. The method of claim 9, wherein the detection agent is a polyclonal antibody.