Predicting mortality and detecting severe disease

• US 10,067,146 B2
• Filed: 01/19/2017
• Issued: 09/04/2018
• Est. Priority Date: 04/24/2006
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Snider, James V., Jacobson, Sven
• Primary Examiner(s): Cheu, Changhwa J
• Application Number:
  US15/410,155
• Publication Number:
  US 20170131294A1
• Time in Patent Office: 593 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2333/54 Interleukins [IL]
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/12 Pulmonary diseases
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

Measurement of circulating ST2 and/or IL-33 concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, and the detection of severe disease.

Claims

1. A method for determining the risk of death within one year in a subject having dyspnea, and treating the subject, the method comprising:

(a) collecting a biological sample from said dyspnea subject at a first time point;

(b) performing an assay to determine a first level of soluble ST2 in said sample from said subject at the first time point;

(c) collecting a biological sample from said dyspnea subject at a second time point;

(d) performing an assay to determine a second level of soluble ST2 in the sample from the subject at the second time point; and

(e) identifying a subject having a second level of soluble ST2 that is equal or elevated as compared to the first level as having an elevated risk of death within one year and

(f) performing imaging studies or cardiac catheterization on, the subject identified as having an elevated risk of death within one year.

2. The method of claim 1, wherein the biological sample in (a) and the biological sample in (b) each comprises serum, blood, or plasma.

3. The method of claim 1, wherein the subject does not have a cardiovascular disorder.

4. The method of claim 1, wherein the subject has a pulmonary disorder.

5. The method of claim 1, further comprising:

Collecting a biological sample and performing an assay to determining a first level of one or more adjunct marker(s) selected from the group consisting of troponin, brain natriuretic peptide (BNP), proBNP, amino-terminal (NT) proBNP, atrial natriuretic peptide (ANP), NT-proBNP, proANP, C-reactive protein, and D-dimers in the subject at the first time point;

And collecting another biological sample and performing an assay to determine a second level of the one or more adjunct biomarker(s) in the subject at the second time point.

6. The method of claim 5, wherein the one or more adjunct biomarker(s) is selected from the group consisting of:

NT-proBNP and BNP.

7. The method of claim 1, wherein the subject has a body mass index (BMI) of 25-29 or renal insufficiency.

8. The method of claim 1, wherein the subject has a BMI of ≥

30.

9. The method of claim 1, wherein the one or more adjunct biomarker is NT-proBNP.

10. The method of claim 1, further comprising obtaining the first and second biological samples from the subject.

11. The method of claim 1, wherein inpatient care of the subject identified as having an elevated risk of death within one year is continued or initiated, or imaging studies or cardiac catheterization is performed on the subject identified as having an elevated risk of death within one year.

12. The method of claim 11, wherein inpatient care of the subject identified as having an elevated risk of death within one year is initiated.

13. The method of claim 11, wherein the inpatient care of the subject identified as having an elevated risk of death within one year is continued.

14. The method of claim 1, wherein the subject identified as having a decreased risk of death within one year is discharged from a hospital or provided care on an outpatient basis.

15. The method of claim 14, wherein the subject identified as having a decreased risk of death within one year is discharged from a hospital.

16. The method of claim 14, wherein the subject identified as having a decreased risk of death within one year is provided care on an outpatient basis.

17. The method of claim 1, wherein the assay to determine the first level of soluble ST2 in (a) and the assay to determine the second level of soluble ST2 in (b) is an immunoassay.

18. The method of claim 17, wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA).

19. The method of claim 18, wherein the ELISA is a sandwich ELISA.

20. The method of 17, wherein the immunoassay utilizes a monoclonal antibody.