Predictive biomarkers for ovarian cancer

• US 10,605,811 B2
• Filed: 11/16/2017
• Issued: 03/31/2020
• Est. Priority Date: 06/29/2007
• Status: Active Grant

• Current Assignee: Aspira Women's Health, Inc.
• Original Assignee: Vermillion, Inc.
• Inventors: Mansfield, Brian C., Yip, Ping F., Amonkar, Suraj, Bertenshaw, Greg P.
• Primary Examiner(s): Shen, Bin
• Application Number:
  US15/815,085
• Publication Number:
  US 20180074064A1
• Time in Patent Office: 866 Days
• 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 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/57449 of ovaries
• 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 are provided for predicting the presence, subtype and stage of ovarian cancer, as well as for assessing the therapeutic efficacy of a cancer treatment and determining whether a subject potentially is developing cancer. Associated test kits, computer and analytical systems as well as software and diagnostic models are also provided.

Claims

1. An article of manufacture comprising a set of reagents to measure the levels of a panel of biomarkers in a specimen, wherein the panel of biomarkers comprise CA125, Apo A1, HE4, and FSH, and their measurable fragments, and wherein the set of reagents are bound to a solid support and specifically bind to said biomarkers.

2. The set of reagents of claim 1, wherein the reagents are binding molecules.

3. The set of reagents of claim 2, wherein the binding molecules are antibodies.

4. A test kit comprising the set of reagents of claim 1.

5. A multianalyte panel assay comprising the set of reagents of claim 1.

6. A method of predicting the likelihood of cancer in a subject, comprising:

detecting the levels of biomarkers in a specimen using the set of reagents of claim 1, wherein a change in the levels of the biomarkers, as compared with a control group of patients who do not have cancer, is predictive of cancer in that subject.

7. The method of claim 6, wherein the cancer is ovarian cancer.

8. The method of claim 7, wherein a change in the relative levels of the biomarkers is determined.

9. The method of claim 7, wherein the specimen is selected from the group consisting of blood, serum, plasma, lymph, cerebrospinal fluid, ascites, urine and tissue biopsy.

10. The method of claim 7, wherein the ovarian cancer is selected from the group consisting of serous, endometrioid, mucinous, and clear cell cancer.

11. The method of claim 7, wherein the prediction of ovarian cancer includes a stage selected from the group consisting of Stage IA, IB, IC, II, III and IV tumors.

12. The method of claim 7, further comprising creating a report of the relative levels of the biomarkers.

13. The method of claim 12, wherein the report includes the prediction as to the presence or absence of ovarian cancer in the subject or the stratified risk of ovarian cancer for the subject, optionally by stage of cancer.

14. The method of claim 7, wherein the sample is taken from a subject selected from the group consisting of subjects who are symptomatic for ovarian cancer and subjects who are at high risk for ovarian cancer.

15. The method of claim 7, wherein the method has a sensitivity of at least about 85 percent and a specificity of at least about 85 percent.

16. The method of claim 15, wherein the sensitivity and specificity are determined for a population of women who are symptomatic for ovarian cancer and have ovarian cancer as compared with a control group of women who are symptomatic for ovarian cancer but who do not have ovarian cancer.

17. A method to assess the therapeutic efficacy of a cancer treatment, comprising:

comparing the biomarker profiles in specimens taken from a subject before and after the treatment or during the course of treatment with a set of reagents according to claim 1, wherein a change in the biomarker profile over time toward a non-cancer profile or to a stable profile is interpreted as efficacy.

18. A method for determining whether a subject potentially is developing cancer, comprising:

comparing the biomarker profiles in specimens taken from a subject at two or more points in time with a set of reagents according to claim 1, wherein a change in the biomarker profile toward a cancer profile, is interpreted as a progression toward developing cancer.