Method for diagnosing or monitoring kidney function or diagnosing kidney dysfunction
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Publication Number
US-10114029-B2
Publication Date
2018-10-30
Expiration Date
Abstract
A method for (a) diagnosing or monitoring kidney function in subject or (b) diagnosing kidney dysfunction in a subject or (c) predicting or monitoring the risk of an adverse events in a diseased subject or (d) predicting or monitoring the success of a therapy or intervention comprising determining the level of Pro-Enkephalin (PENK) or fragments thereof of at least 5 amino acids in a bodily fluid obtained from said subject; and correlating said level of Pro-Enkephalin or fragments thereof with (a) kidney function in a subject or(b) kidney dysfunction in said subject or(c) enhanced risk of adverse events or(d) success of a therapy or intervention in a diseased subject.
Core Innovation
The invention relates to methods for diagnosing or monitoring kidney function, diagnosing kidney dysfunction, and predicting or monitoring risk of adverse events in a subject with kidney disease, as well as predicting or monitoring the success of a therapy or intervention. The methods determine and record the level of Pro-Enkephalin or fragments thereof in a bodily fluid obtained from a subject and use correlation with at least one additional clinical parameter to evaluate kidney function, kidney dysfunction, adverse events, or therapy success.
The Pro-Enkephalin or fragments thereof are one or more of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 5, SEQ ID No. 6, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10 or SEQ ID No. 11, and the level is determined using a binder. The binder binds to Pro-Enkephalin or a fragment thereof and does not bind to enkephalin peptides [Met]enkephalin SEQ ID No: 3, including embodiments where the binder binds to a region within an amino acid sequence selected from defined SEQ ID numbers.
The methods further determine at least one additional clinical parameter selected from age, BUN, NGAL, Creatinine Clearance, Creatinine, urea, or Apache Score, and correlate the Pro-Enkephalin level with kidney function or kidney dysfunction. When the Pro-Enkephalin or fragment level is elevated above a certain threshold, it is predictive or diagnostic for kidney dysfunction and predictive for enhanced risk of adverse events, including worsening of kidney dysfunction including kidney failure, loss of kidney function, end-stage kidney disease, or death due to kidney dysfunction; when the level is below a certain threshold, it is predictive for success of therapy or intervention.
Claims Coverage
The partial set includes five independent claims. Across these claims, the inventive features center on measuring Pro-Enkephalin or specified fragments in a bodily fluid using a binder that excludes binding to [Met]enkephalin SEQ ID No: 3, then correlating with additional clinical parameters with threshold-based predictive and diagnostic logic for kidney function, kidney dysfunction, adverse event risk, and therapy success.
Pro-Enkephalin level determination with selective binder non-binding to Met-enkephalin
Determining and recording the level of Pro-Enkephalin or fragments thereof in a bodily fluid obtained from said subject with kidney disease using a binder to Pro-Enkephalin or a fragment thereof wherein said Pro-Enkephalin or fragment thereof is one or more of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 5, SEQ ID No. 6, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10 or SEQ ID No. 11 and wherein said binder does not bind to SEQ ID No: 3.
Correlating biomarker level with additional clinical parameters for kidney function, dysfunction, and outcomes
Determining at least one additional clinical parameter of said subject which is age, BUN, NGAL, Creatinine Clearance, Creatinine, urea, or Apache Score.
Pro-Enkephalin fragment level correlation with threshold-based prediction of kidney dysfunction, adverse events, and therapy success
Determining the level of Pro-Enkephalin fragments in a bodily fluid obtained from a subject using a binder to said Pro-Enkephalin fragments and determining at least one additional clinical parameter from said subject that is age, BUN, NGAL, Creatinine Clearance, Creatinine or Apache Score, correlating said level of said Pro-Enkephalin fragments and at least one additional clinical parameter with kidney function or kidney dysfunction wherein an elevated level above a certain threshold is predictive or diagnostic for kidney dysfunction, or with risk of an adverse event wherein an elevated level above a certain threshold is predictive for enhanced risk, or with success of a therapy or intervention wherein a level below a certain threshold is predictive for success.
Binder binds Pro-Enkephalin without binding to Met-enkephalin and with region-based amino-acid sequence binding specification
A binder binds to a region within an amino acid sequence selected from the group consisting of SEQ ID No. 1, 2, 5, 6, 7, 8, 9, 10 and 11 and does not bind to enkephalin peptides [Met]enkephalin SEQ ID No:3.
Assay and kit embodiments for kidney function diagnostics and monitoring
A method for diagnosing or monitoring kidney function using a kit or assay to detect Pro-Enkephalin or fragments thereof in a subject, wherein said kit or assay comprises at least one antibody capable of binding Pro-Enkephalin or fragments thereof in a sample of bodily fluid obtained from said subject which does not bind to enkephalin peptides [Met]enkephalin SEQ ID No: 3, and additionally using an assay for determining at least one additional clinical parameter selected from BUN, NGAL, Creatinine Clearance, Creatinine or Apache Score and correlating with kidney function, kidney dysfunction, risk of an adverse event, or success of a therapy or intervention.
Threshold-based therapy-success prediction and adverse-outcome correlation
A method of using a kit or assay to detect Pro-Enkephalin or fragments thereof in a subject, wherein said kit or assay comprises at least one antibody capable of binding Pro-Enkephalin or fragments thereof in a sample of bodily fluid obtained from said subject, which does not bind to enkephalin peptides [Met]enkephalin SEQ ID No: 3, said method comprising determining the level using at least one antibody within said kit or assay that binds Pro-Enkephalin or fragments thereof which does not bind to enkephalin peptides [Met]enkephalin SEQ ID No: 3 wherein a level below 80 pmol/L is predictive for a success of therapy or intervention or a level above 80 pmol/L is correlated with a risk of death or an adverse event or is predictive or diagnostic for kidney dysfunction.
Across the independent claims, the core coverage is for kidney-function and kidney-dysfunction related diagnosis, monitoring, and prognostic stratification by quantifying Pro-Enkephalin or specified fragments in bodily fluid using a binder or antibody that does not bind to [Met]enkephalin SEQ ID No: 3, followed by correlation with additional clinical parameters using threshold-based predictive and diagnostic rules for kidney dysfunction, adverse event risk, and therapy success.
Stated Advantages
Not explicitly described in patent.
Documented Applications
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