Diagnosis of sepsis

• US 10,443,099 B2
• Filed: 09/10/2015
• Issued: 10/15/2019
• Est. Priority Date: 04/15/2005
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Garrett, James A., Wang, Sha-Sha, Thornton, Keith, Moore, Richard L., Keating, William, Nussbaumer, William A., Whiteford, Craig C.
• Primary Examiner(s): Kapushoc, Stephen T
• Application Number:
  US14/850,933
• Publication Number:
  US 20160168638A1
• Time in Patent Office: 1,496 Days
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6888 for detection or identification of organisms
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 2333/5412 IL-6
• CPC Class Codes: G01N 2333/5421 IL-8
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Methods for predicting the development of sepsis in a subject at risk for developing sepsis are provided. In one method, features in a biomarker profile of the subject are evaluated. The subject is likely to develop sepsis if these features satisfy a particular value set. Methods for predicting the development of a stage of sepsis in a subject at risk for developing a stage of sepsis are provided. In one method, a plurality of features in a biomarker profile of the subject is evaluated. The subject is likely to have the stage of sepsis if these feature values satisfy a particular value set. Methods of diagnosing sepsis in a subject are provided. In one such method, a plurality of features in a biomarker profile of the subject is evaluated. The subject is likely to develop sepsis when the plurality of features satisfies a particular value set.

Claims

1. A method of treating sepsis in a subject at risk for developing sepsis, the method comprising:

obtaining from at least one blood sample taken from a SIRS-positive subject an expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid;

determining that the subject is likely to develop sepsis based on the expression level of each of IL-6 protein, IL-8 protein, VNN-1 nucleic acid and GADD45B nucleic acid being elevated compared to a control expression level of each, wherein said control expression level of each is from SIRS patients that did not develop sepsis; and

administering to said subject that is determined to be likely to develop sepsis a therapeutically effective sepsis treatment regimen.

2. The method of claim 1, wherein the at least one blood sample was taken from said subject at a single point in time.

3. The method of claim 1, wherein the expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid is determined from a plurality of blood samples taken from said subject at different points in time.

4. The method of claim 3, wherein at least one of the expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid indicates whether the expression level of said biomarker is increasing or decreasing over time.

5. The method of claim 3, wherein a first blood sample in said plurality of blood samples is taken on a first day before the subject acquires sepsis and a second blood sample in said plurality of blood samples is taken on a second day before the subject acquires sepsis.

6. The method of claim 1, the method further comprising constructing, prior to the determining step, a biomarker profile of said subject comprising the expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid.

7. The method of claim 6, wherein the constructing step comprises applying a data analysis algorithm to the expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid of the subject, wherein the data analysis algorithm is derived from an expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid that are obtained from members of a population.

8. The method of claim 7, wherein said population comprises subjects that develop sepsis subsequent to obtaining said expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid and subjects that do not develop sepsis subsequent to obtaining said expression level of IL-6 protein, IL-8 protein, VNN-1 nucleic acid, and GADD45B nucleic acid.

9. The method of claim 2, wherein the expression level of IL-6 protein and IL-8 protein in said blood sample was determined using a method comprising detection via interaction with protein-specific antibodies.

10. The method of claim 9, wherein one or more of the protein-specific antibodies is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, an antibody fragment, a scFv fragment, a Fab fragment, a F(ab′

)₂ fragment.