Method for diagnosing or monitoring kidney function or diagnosing kidney dysfunction
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11016107-B2
Publication Date
2021-05-25
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 disclosure relates to diagnosing or monitoring kidney function in a subject by determining the level of Pro-Enkephalin (PENK) or fragments thereof of at least 5 amino acids in a bodily fluid obtained from the subject. The method includes follow-up measurements of the level, performed more than once in one subject, and a relative change of PENK or the fragments during follow-up is used as a correlation with kidney function status.
In the follow-up measurement, a lowered relative change of Pro-Enkephalin or fragments thereof of at least 5 amino acids correlates with improvement of the subject’s kidney function, while an increased relative change correlates with worsening of the subject’s kidney function. The disclosure specifies that PENK is Pro-Enkephalin (SEQ ID No. 1) or MR-Pro-Enkephalin (MRPENK; SEQ ID No. 6), and that the monitoring supports evaluation of improvement versus worsening based on the direction of relative change during follow-up.
An assay is used that comprises two binders binding to two different regions within the region of Pro-Enkephalin, specifically amino acid 133-140 (LKELLETG, SEQ ID No. 13) and amino acid 152-159 (SDNEEEVS, SEQ ID No. 14), wherein each region comprises at least 4 or 5 amino acids. The disclosed approaches include binder-based immunoreactive detection using binders such as antibodies, antibody fragments, non-Ig scaffolds, or aptamers that bind defined PENK regions or sequence fragments.
Claims Coverage
Two independent claims are provided. Across both independent claims, the core coverage is directed to repeated determination and follow-up relative change assessment of Pro-Enkephalin or fragments of at least 5 amino acids in a bodily fluid, correlated with improvement or worsening of kidney function, using a two-binder assay that binds two defined PENK regions.
Repeated determination and relative-change monitoring of Pro-Enkephalin for kidney function
A method for diagnosing or monitoring kidney function in a subject comprising determining the level of Pro-Enkephalin or fragments thereof of at least 5 amino acids in a bodily fluid, and monitoring kidney function with a follow-up measurement of the level wherein during follow-up a relative change that is lowered correlates with improvement of the subject’s kidney function, or a relative change that is increased correlates with the worsening of the subject’s kidney function, wherein the determination is performed more than once in one subject.
Two-binder assay binding to two different PENK regions
An assay is used comprising two binders that bind to two different regions within the region of Pro-Enkephalin, amino acid 133-140 (LKELLETG, SEQ ID NO. 13) and amino acid 152-159 (SDNEEEVS, SEQ ID NO. 14), wherein each of said regions comprises at least 4 or 5 amino acids.
Specific Pro-Enkephalin targets by SEQ ID No. 1 or SEQ ID No. 6
Wherein said Pro-Enkephalin or fragment thereof is SEQ ID No. 1, or SEQ ID No. 6.
Additional clinical parameter determination during diagnosis or monitoring
Additionally at least one clinical parameter is determined that is age, BUN, NGAL, Creatinine Clearance, Creatinine or Apache Score.
The independent claim set covers diagnosing or monitoring kidney function by repeatedly measuring Pro-Enkephalin or fragments of at least 5 amino acids in a bodily fluid and correlating the direction of follow-up relative change with improvement or worsening. The claims further require an assay format using two binders recognizing two defined PENK regions and include identification of PENK targets by SEQ ID No. 1 or SEQ ID No. 6, with an option to determine at least one clinical parameter among age, BUN, NGAL, creatinine clearance, creatinine, or Apache score.
Stated Advantages
Use of PENK levels and relative changes correlates with kidney function/dysfunction, including risk of adverse events, including death, and success of therapy/intervention.
Inflammation-independent thresholding using a single cut-off usable across populations is described.
Documented superiority compared with conventional markers including NGAL, creatinine, creatinine clearance, cystatin C, and urea.
Early biomarker utility is described.
Documented Applications
Diagnosing or monitoring kidney function in a subject, including follow-up monitoring where improvement or worsening correlates with relative change in Pro-Enkephalin or fragments of at least 5 amino acids.
Assessing response to preventive and/or therapeutic measures by monitoring kidney function.
Risk assessment for adverse events including death, associated with PENK levels and relative changes.
Supporting success of therapy or intervention, including renal replacement therapy, associated with PENK levels and relative changes.
Evaluation of kidney dysfunction based on RIFLE-defined worsening or dysfunction, supported by diagnostic performance described for PENK.
Interested in licensing this patent?