Claims for Patent: 8,673,574

Summary for Patent: 8,673,574

Title:	Diagnosis and monitoring of renal failure using peptide biomarkers
Abstract:	Methods for the determination of renal failure, especially chronic renal failure and acute kidney injury, by measurement of peptide or protein biomarkers are described. The methods are useful to determine stages of renal failure, especially the early stages such as stage 1, 2, and 3 of chronic renal failure and stages R and I of acute kidney injury. Furthermore there are described peptides and test kits used in the invention. The described methods are intended to replace or complement the measurement of creatinine and/or cystatin C and/or NGAL for diagnosis of renal failure.
Inventor(s):	Tammen; Harald (Hanover, DE), Honda; Leif (Rye, NH), Jurgens; Michael (Hanover, DE), Peck; Andrew (Waltham, MA)
Assignee:	PxBioSciences LLC (Waltham, MA)
Application Number:	12/544,605
Patent Claims:	1. A method of identifying a subject having or at risk of developing a renal disorder, comprising: a. obtaining a test biological sample from said subject; b. determining a quantity of a peptide biomarker in said test sample, wherein said biomarker consists of SEQ ID NO: 2; c. obtaining a control biological sample from a control subject not having and not at risk of developing said renal disorder; d. determining a quantity of said biomarker in said control sample; and e. comparing said quantity of said biomarker in said test sample and in said control sample; wherein a variance in said quantity of said biomarker in said test sample relative to in said control sample indicates that said subject has or is at risk of developing said renal disorder. 2. A method of identifying a subject having or at risk of developing a renal disorder, comprising: a. obtaining a test biological sample from said subject; b. determining a quantity of a peptide biomarker in said test sample, wherein said biomarker consists of SEQ ID NO: 2; and c. comparing said quantity of said biomarker with a predetermined reference value; wherein an increase in said quantity of said biomarker in said test sample relative to said reference value indicates that said subject has or is at risk of developing said renal disorder. 3. A method of monitoring progression of a renal disorder in a subject in need thereof, comprising: a. obtaining a test biological sample from said subject; b. determining a quantity of a peptide biomarker in said test sample, wherein i) said biomarker consists of SEQ ID NO: 2, and ii) said quantity of said biomarker correlates to a stage of said renal disorder; c. repeating steps a and b over a period of time; and d. comparing said quantities of said biomarker over said period of time; wherein a difference in said quantities of said biomarker over said period of time indicates progression of said renal disorder. 4. A method of monitoring efficacy of a renal disorder therapy in a subject in need thereof, comprising: a. obtaining a test biological sample from said subject; b. determining a quantity of a peptide biomarker in said test sample, wherein i) said biomarker consists of SEQ ID NO: 2, and ii) said quantity of said biomarker correlates to a stage of said renal disorder; c. treating said subject with a renal disorder therapy; d. repeating steps a and b; and e. comparing said quantity of said biomarker prior to and subsequent to the treatment; wherein a difference of said quantity of said biomarker prior to and subsequent to the treatment indicates efficacy of said renal disorder therapy. 5. The method of any one of claims 1-4, wherein the subject has a condition selected from the group consisting of injury to a kidney, type 2 diabetes, hypertension, cardiovascular disease, sepsis, hemorrhage, massive blood loss, congestive heart failure, decompensated liver cirrhosis, damaged kidney blood vessels, obstructions of urine collection systems or extra-renal drainage, vasculitis, malignant hypertension, acute glomerulonephritis, acute interstitial nephritis, and acute tubular necrosis. 6. A method of determining an effect of an event on renal function in a subject in need thereof, comprising: a. obtaining a first test biological sample from said subject prior to said event; b. obtaining a second test biological sample from said subject subsequent to said event; c. determining a quantity of a peptide biomarker in said first test sample and in said second test sample, wherein i) said biomarker consists of SEQ ID NO: 2, and ii) said quantity of said biomarker correlates to a stage of said renal disorder; and d. comparing said quantity of said biomarker in said first test sample and in said second test sample; wherein a difference of said quantity of said biomarker in said first test sample and in said second test sample indicates the effect of said event on renal function. 7. The method of claim 6, wherein said event is selected from the group consisting of exposure to a substance, exposure to a living organism, food ingestion, alcohol ingestion, consumption of tobacco products, exposure to stress, and physical activity. 8. The method of claim 7, wherein said substance is selected from the group consisting of a medication, a chemical, and a toxin. 9. The method of claim 7, wherein said living organism is selected from the group consisting of a plant, an animal, a microbe, and a virus. 10. The method of any one of claims 1-4 and 6, wherein said renal disorder is chronic renal failure, and wherein said stage is selected from the group consisting of Stages 1, 2, 3, 4, and 5 of chronic renal failure. 11. The method of any one of claims 1-4 and 6, wherein said renal disorder is acute renal failure, and wherein said stage is selected from the group consisting of Stages Normal, and R, I, F, L, and E of acute renal failure. 12. The method of claim 4, wherein said renal disorder therapy is a renal replacement therapy selected from the group consisting of medication, hemodialysis and kidney transplantation. 13. The method of any one of claims 1-4 and 6, wherein the step of determining said quantity of said biomarker comprises calculating glomerular filtration rate. 14. The method of claim 13, wherein the step of determining said quantity of said biomarker is accomplished by an immunological method, a molecular biologic method, or a physical method. 15. The method of claim 14, wherein said immunological method is selected from the group consisting of an ELISA assay, an RIA assay, an ELI-Spot assay, a flow cytometry assay, an immunohistochemistry assay, a Western blot analysis, and a protein chip assay. 16. The method of claim 14, wherein said molecular biologic method is selected from the group consisting of a PCR analysis, a RT-PCR analysis, a TaqMan PCR analysis, a nucleic acid chip assay, in situ hybridization, a nucleic acid dot blot analysis, a nucleic acid slot blot analysis, a Southern blot analysis and a Northern blot analysis. 17. The method of claim 14, wherein said physical method is selected from the group consisting of a mass spectrometric method, a FRET assay, a chromatographic assay, and a dye-detection assay. 18. The method of claim 17, wherein said mass spectrometric method is selected from the group consisting of MALDI, ESI, ionspray, thermospray, MCI, FAB, SELDI, ICAT, iTRAQ, and affinity mass spectrometric method. 19. The method of claim 13, wherein the step of determining said quantity of said biomarker is accomplished by nuclear magnetic resonance (NMR), fluorometry, colorimetry, radiometry, luminometry, liquid chromatography, capillary chromatography, thin-layer chromatography, plasmon-resonance (e.g. BIACORE), and one- or two-dimensional gel electrophoresis. 20. The method of any one of claims 1-4 and 6, wherein said biological sample is selected from the group consisting of blood, plasma, serum, hemofiltrate, urine, kidney tissue, in vitro cultured kidney cell lines, in vitro cultured primary kidney cells, in vitro cultured kidney tissue, in vitro cultured kidney organ, and supernatants from in vitro cell culture, tissue culture, or organ culture. 21. The method of claim 20, further comprising fractionating said biological sample prior to the step of determining the quantity of the peptide biomarker in said test sample. 22. The method of claim 21, wherein fractionating said biological sample is accomplished through a method selected from the group consisting of a chromatography method, a filtration method, a capillary electrophoresis method, a gel electrophoresis method, a liquid extraction method, a precipitation method, and an immunoprecipitation method. 23. The method of claim 22, wherein said chromatography method is reverse phase chromatography. 24. The method of any one of claims 1-4 and 6, further comprising calculating glomerular filtration rate by measuring clearance of an endogenic substance. 25. The method of claim 24, wherein said endogenic substance is selected from the group consisting of serum creatinine, Cystatin C, NGAL, urea, interleukin 18, intestinal form of alkaline phosphatease, N-acetyl-beta-gulcosaminidase, alanine-aminopeptidase, kidney injury molecule 1, parathyroid hormone, creatol, creatine kinase, methylguanidine, and 1,5-anhydroglucitol (1,5-AG). 26. The method of any one of claims 1-4 and 6, further comprising a step selected from the group consisting of determining the size of the kidneys, measuring urine output, analyzing urine sediments, and analyzing excretion of sodium or urea. 27. The method of claim 26, wherein the size of the kidneys is determined using an imaging technique. 28. The method of claim 27, wherein said imaging technique is ultrasound. 29. The method of any one of claims 1-4 and 6, wherein said subject is selected from the group consisting of a human, a primate, a mouse, a dog, a pig, and a rat. 30. The method of any one of claims 1-4 and 6, wherein determining the quantity of a peptide biomarker comprises contacting the test sample with an antibody or antigen binding fragment thereof that specifically binds to the peptide biomarker consists of SEQ ID NO: 2.

Details for Patent 8,673,574

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2028-08-21