Claims for Patent: 8,993,250

Summary for Patent: 8,993,250

Title:	Methods and compositions for diagnosis and prognosis of renal injury and renal failure
Abstract:	The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Clusterin, Heart-type fatty acid binding protein, Hepatocyte growth factor, Interferon gamma, Interleukin-12 subunit beta, Interleukin-16, Interleukin-2, 72 kDa type IV collagenase, Matrix metalloproteinase-9, Midkine, and Serum amyloid P-component as diagnostic and prognostic biomarkers in renal injuries.
Inventor(s):	Anderberg; Joseph (Encinitas, CA), Gray; Jeff (Solana Beach, CA), McPherson; Paul (Encinitas, CA), Nakamura; Kevin (Cardiff by the Sea, CA)
Assignee:	Astute Medical, Inc. (San Diego, CA)
Application Number:	13/128,392
Patent Claims:	1. A method for evaluating renal status in a subject, comprising: obtaining a urine sample from a subject selected for evaluation based on a determination that the subject is at risk of a future acute renal injury; performing one or more assays configured to detect a kidney injury marker selected from the group consisting of Clusterin, Heart-type fatty acid binding protein, Hepatocyte growth factor, Interferon gamma, Interleukin-12 subunit beta, Interleukin-16, Interleukin-2, 72 kDa type IV collagenase, Matrix metalloproteinase-9, Midkine, and Serum amyloid P-component by introducing the urine sample obtained from the subject into an assay instrument which (i) contacts the urine sample with one or more antibodies which specifically bind for detection the biomarker(s) which are assayed, and (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to a respective antibody to provide one or more assay results; and correlating the assay result(s) generated by the assay instrument to the renal status of the subject, wherein said correlation step comprises correlating the assay result(s) to one or more of risk stratification, staging, prognosis, classifying and monitoring of the renal status of the subject, wherein said correlating step comprises assigning a likelihood of one or more future changes in renal status to the subject based on the assay result(s). 2. A method according to claim 1, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF). 3. A method according to claim 2, wherein said assay result(s) comprise one or more of: (i) a measured concentration of Clusterin, (ii) a measured concentration of Heart-type fatty acid binding protein, (iii) a measured concentration of Hepatocyte growth factor, (iv) a measured concentration of Interferon gamma, (v) a measured concentration of Interleukin-12 subunit beta, (vi) a measured concentration of Interleukin-16, (vii) a measured concentration of Interleukin-2, (viii) a measured concentration of 72 kDa type IV collagenase, (ix) a measured concentration of Matrix metalloproteinase-9, (x) a measured concentration of Midkine, or (xi) a measured concentration of Serum amyloid P-component, and said correlation step comprises, for each assay result, comparing said measure concentration to a threshold concentration, and for a positive going marker, assigning an increased likelihood of suffering a future injury to renal function, future reduced renal function, future ARF, or a future improvement in renal function to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold or assigning a decreased likelihood of suffering a future injury to renal function, future reduced renal function, future ARF, or a future improvement in renal function to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold, or for a negative going marker, assigning an increased likelihood of suffering a future injury to renal function, future reduced renal function, future ARF, or a future improvement in renal function to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold or assigning a decreased likelihood of suffering a future injury to renal function, future reduced renal function, future ARF, or a future improvement in renal function to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. 4. A method according to claim 1, wherein said one or more future changes in renal status comprise a clinical outcome related to a renal injury suffered by the subject. 5. A method according to claim 1, wherein said assay result(s) comprise one or more of: (i) a measured concentration of Clusterin, (ii) a measured concentration of Heart-type fatty acid binding protein, (iii) a measured concentration of Hepatocyte growth factor, (iv) a measured concentration of Interferon gamma, (v) a measured concentration of Interleukin-12 subunit beta, (vi) a measured concentration of Interleukin-16, (vii) a measured concentration of Interleukin-2, (viii) a measured concentration of 72 kDa type IV collagenase, (ix) a measured concentration of Matrix metalloproteinase-9, (x) a measured concentration of Midkine, or (xi) a measured concentration of Serum amyloid P-component, and said correlation step comprises, for each assay result, comparing said measure concentration to a threshold concentration, and for a positive going marker, assigning an increased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold, or assigning a decreased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold, or for a negative going marker, assigning an increased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold, or assigning a decreased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. 6. A method according to claim 1, wherein the likelihood of one or more future changes in renal status is that an event of interest is more or less likely to occur within 30 days of the time at which the urine sample is obtained from the subject. 7. A method according to claim 6, wherein the likelihood of one or more future changes in renal status is that an event of interest is more or less likely to occur within a period selected from the group consisting of 21 days, 14 days, 7 days, 5 days, 96 hours, 72 hours, 48 hours, 36 hours, 24 hours, and 12 hours. 8. A method according to claim 1, wherein the subject is selected for evaluation of renal status based on the pre-existence in the subject of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF. 9. A method according to claim 1, wherein the subject is selected for evaluation of renal status based on an existing diagnosis of one or more of congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, glomerular filtration below the normal range, cirrhosis, serum creatinine above the normal range, sepsis, injury to renal function, reduced renal function, or ARF, or based on undergoing or having undergone major vascular surgery, coronary artery bypass, or other cardiac surgery, or based on exposure to NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin. 10. A method according to claim 1, wherein said correlating step comprises assigning a diagnosis of the occurrence or nonoccurrence of one or more of an injury to renal function, reduced renal function, or ARF to the subject based on the assay result(s). 11. A method according to claim 1, wherein said correlating step comprises assessing whether or not renal function is improving or worsening in a subject who has suffered from an injury to renal function, reduced renal function, or ARF based on the assay result(s). 12. A method according to claim 11, wherein said assay result(s) comprise one or more of: (i) a measured concentration of Clusterin, (ii) a measured concentration of Heart-type fatty acid binding protein, (iii) a measured concentration of Hepatocyte growth factor, (iv) a measured concentration of Interferon gamma, (v) a measured concentration of Interleukin-12 subunit beta, (vi) a measured concentration of Interleukin-16, (vii) a measured concentration of Interleukin-2, (viii) a measured concentration of 72 kDa type IV collagenase, (ix) a measured concentration of Matrix metalloproteinase-9, (x) a measured concentration of Midkine, or (xi) a measured concentration of Serum amyloid P-component, and said correlation step comprises, for each assay result, comparing said measure concentration to a threshold concentration, and for a positive going marker, assigning a worsening of renal function to the subject when the measured concentration is above the threshold, or assigning an improvement of renal function when the measured concentration is below the threshold, or for a negative going marker, assigning a worsening of renal function to the subject when the measured concentration is below the threshold, or assigning an improvement of renal function when the measured concentration is above the threshold. 13. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of an injury to renal function in said subject. 14. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of reduced renal function in said subject. 15. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of acute renal failure in said subject. 16. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for renal replacement therapy in said subject. 17. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for renal transplantation in said subject. 18. A method according to claim 3, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 72 hours of the time at which the urine sample is obtained. 19. A method according to claim 3, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 48 hours of the time at which the urine sample is obtained. 20. A method according to claim 3, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 72 hours of the time at which the urine sample is obtained. 21. A method according to claim 3, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 48 hours of the time at which the urine sample is obtained. 22. A method according to claim 3, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 24 hours of the time at which the urine sample is obtained. 23. A method according to claim 5, wherein the increased or decreased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease assigned to the subject is a likelihood that an event of interest is more or less likely to occur within 30 days of the time at which the urine sample is obtained from the subject. 24. A method according to claim 5, wherein the increased or decreased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease assigned to the subject is a likelihood that an event of interest is more or less likely to occur within 72 hours of the time at which the urine sample is obtained from the subject. 25. A method according to claim 5, wherein the increased or decreased likelihood of subsequent acute kidney injury, worsening stage of AKI, mortality, need for renal replacement therapy, need for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, or chronic kidney disease assigned to the subject is a likelihood that an event of interest is more or less likely to occur within 24 hours of the time at which the urine sample is obtained from the subject.

Details for Patent 8,993,250

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2028-11-10