Predictive biomarkers for ovarian cancer
Inventors
Mansfield, Brian C. • Yip, Ping F. • Amonkar, Suraj • Bertenshaw, Greg P.
Assignees
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Publication Number
US-10605811-B2
Publication Date
2020-03-31
Expiration Date
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.
Core Innovation
The invention provides an article of manufacture that includes a set of reagents to measure the levels of a panel of biomarkers in a specimen. The panel comprises CA125, Apo A1, HE4, and FSH, and their measurable fragments, and the set of reagents are bound to a solid support and specifically bind to the biomarkers.
The disclosed system is directed to predicting or detecting epithelial ovarian cancer, including predicting presence or absence and optionally stratifying risk by stage. The disclosure includes biomarker panels for stage-specific predictive panels, along with examples of biomarker lists and panel tables.
The approach is described as a multi-analyte immunoassay that measures biomarker levels from specimens, with downstream reporting based on model-based classification. Statistical and machine learning models are described for classification, including KDE, random forests, classification tree analysis, and support vector machine (SVM).
The disclosure further provides for monitoring progression and therapeutic efficacy by evaluating biomarker-profile changes over time. Biomarker profiles from specimens collected before versus after (or during) cancer treatment are compared, and shifts toward a non-cancer profile or a stable profile are used as indicators.
Claims Coverage
The independent claim set includes one independent claim directed to an article of manufacture for measuring a specific biomarker panel on a solid support. Inventive features are centered on the defined biomarker panel and solid-support bound, specifically binding reagents, with dependent claim refinements covering specimen selection, report content, performance thresholds, sensitivity/specificity evaluation population, and longitudinal biomarker comparisons for therapeutic efficacy.
Solid-support bound biomarker panel reagents
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.
Epithelial ovarian cancer report with optional stage risk stratification
The report includes prediction of presence or absence of ovarian cancer and optionally stratified risk by stage.
Longitudinal biomarker-profile comparison for therapeutic efficacy
Therapeutic efficacy is assessed by comparing biomarker profiles in specimens collected before vs after (or during) treatment, where shifts toward a non-cancer or stable profile indicate efficacy.
Defined evaluation of sensitivity and specificity using symptomatic cohorts
Sensitivity and specificity are determined for symptomatic women with ovarian cancer versus a control group of symptomatic women without ovarian cancer.
Performance threshold for sensitivity and specificity
The method has sensitivity of at least about 85% and specificity of at least about 85%.
Defined specimen sources for biomarker measurement
The specimen is selected from blood, serum, plasma, lymph, cerebrospinal fluid, ascites, urine, or tissue biopsy.
Across the independent claim and its dependent refinements, the claim coverage centers on a solid-support bound set of reagents that specifically bind CA125, Apo A1, HE4, and FSH (and measurable fragments) for measuring biomarker levels in a specimen. The dependent claim refinements further specify report content, sensitivity/specificity determination in symptomatic cohorts, explicit performance thresholds, defined specimen sources, and longitudinal biomarker-profile comparison to assess therapeutic efficacy.
Stated Advantages
Enables prediction of presence or absence of ovarian cancer and optionally stratified risk by stage.
Supports monitoring progression and assessing therapeutic efficacy using biomarker-profile changes over time.
Provides assay performance characterized by sensitivity and specificity thresholds.
Documented Applications
Diagnosing or detecting epithelial ovarian cancer by predicting presence or absence, optionally including stratified risk by stage.
Monitoring progression of ovarian cancer and assessing therapeutic efficacy by comparing biomarker profiles from specimens collected before versus after (or during) treatment.
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