# US 11,439,713 B2 · Method for creating a renal injury model to screen molecules for the treatment of renal injury > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,713 B2 - Document ID: US11439713B2 - Status: Granted - Kind: B2 - Application number: 16/493,613 - Filed: 2018-03-02 - Published: 2020-01-02 - Granted: 2022-09-13 - Earliest claimed: 2017-03-13 - Assignees: Bayer Aktiengesellschaft - Applicants: Bayer Aktiengesellschaft - Inventors: Simone Romoli; Tobias Bauch; Karoline Dröbner - Web page: https://patentgrep.com/patent/US11439713B2 ## CPC - A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure} - G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics} - G01N 33/6827: {Total protein determination, e.g. albumin in urine} - G01N 33/70: involving creatine or creatinine - A01K 2267/035: Animal model for multifactorial diseases - A01K 2267/0393: Animal model comprising a reporter system for screening tests - G01N 2500/00: Screening for compounds of potential therapeutic value - G01N 2800/347: Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS ## Abstract The present invention is related to short-term renal injury models and methods for creating these models. The models and methods can be used for identifying, testing or characterizing candidate molecules with respect to their suitability to treat renal injury. The methods comprise a step of inducing, in a test subject, renal injury by administering subcutaneously a bolus of a renal injury inducer, in a dosage sufficiently high to induce renal injury. Different types of readout for renal injury are provided such as albumin creatinine ratio (ACR) determined in a urine sample taken from the subject, or the development of transcutaneous fluorescence after injection of a fluorescent molecule. Based on the readout the degree of renal injury and/or alteration of GFR can be determined. ## Claims ### Claim 1 A method for creating a renal injury model, wherein the method comprises the following steps: a) inducing, in a test subject, renal injury by administering subcutaneously and/or intravenously a bolus of a renal injury inducer, in a dosage sufficiently high to induce renal injury, b) determining at least the albumin creatinine ratio (ACR) in a urine sample taken from the test subject, and c) determining from the ACR determined in step b) the degree of renal injury that has been induced in the test subject, wherein the renal injury inducer is selected from the group consisting of angiotensin II, vasopressin, Sema3a and heparanase. ### Claim 2 (depends on 1) The method according to claim 1, wherein the test subjects are rodents. ### Claim 3 (depends on 2) The method according to claim 2, wherein the rodents are mice or rats. ### Claim 4 (depends on 1) The method according to claim 1, wherein the determination of the ACR is carried out between ≥2 hrs and ≤6 hrs after administration of the bolus of renal injury inducer. ### Claim 5 A method of identifying, testing or characterizing a candidate molecule for its suitability to treat renal injury, wherein the method comprises the following steps: a) inducing, in a test subject, renal injury by administering subcutaneously and/or intravenously a bolus of a renal injury inducer, in a dosage sufficiently high to induce renal injury, b) administering to the subject a candidate molecule, c) determining at least the ACR in a urine sample taken from the subject, and d) deducing, from the ACR determined in step c), whether or not the candidate molecule is capable of treating the renal injury induced in the test subject, wherein the renal injury inducer is selected from the group consisting of angiotensin II, vasopressin, Sema3a and heparanase. ### Claim 6 (depends on 5) The method according to claim 5, wherein one or more candidate molecules are administered to the test subject, and further wherein the one or more candidate molecules are administered intravenously, subcutaneously, intraperitoneally or per oral application. ### Claim 7 A method for screening a population of candidate molecules for their suitability to treat renal injury, wherein the method comprises the following steps: a) inducing, in at least two test subjects, renal injury by administering subcutaneously and/or intravenously a bolus of a renal injury inducer, in a dosage sufficiently high to induce renal injury, b) administering to the test subjects molecules from a library of candidate molecules, c) determining at least the ACR in urine samples taken from the subjects, and d) deducing, from the ACR determined in step c), whether or not the molecules are capable of treating the renal injury induced in the test subjects, wherein the renal injury inducer is selected from the group consisting of angiotensin II, vasopressin, Sema3a and heparanase. ### Claim 8 A method for creating a renal injury model, wherein the method comprises the following steps: a) inducing, in a test subject, renal injury by administering subcutaneously and/or intravenously a bolus of a first renal injury inducer, and a second bolus of the same or a different renal injury inducer, in a dosage sufficiently high to induce renal injury together with the bolus of the first renal injury inducer, b) determining at least the albumin creatinine ratio (ACR) in a urine sample taken from the test subject, and c) determining from the ACR determined in step b) the degree of renal injury that has been induced in the test subject, wherein the renal injury inducer is selected from the group consisting of angiotensin II, vasopressin, Sema3a and heparanase. ### Claim 9 (depends on 8) The method according to claim 8, wherein the two boli of injury inducer are administered simultaneously, or in sequence. ### Claim 10 A method of identifying, testing or characterizing a candidate molecule for its suitability to treat renal injury, wherein the method comprises the following steps: a) inducing, in a test subject and in a control subject, renal injury by administering subcutaneously and/or intravenously a bolus of a renal injury inducer, in a dosage sufficiently high to induce renal injury, wherein the test subject and the control subject are administered the same renal injury inducer in the same dosage, b) administering to the test subject a candidate molecule, c) administering to the control subject (i) none of the candidate molecule, (ii) a placebo, and/or (iii) a positive control that is a molecule suitable for the treatment of renal injury, d) determining at least the ACR in a urine sample taken from the subject and the ACR in a urine sample taken from the control subject, e) comparing the ACR determined from the test subject and the control subject, f) deducing, from the ACR comparison in step e), whether or not the candidate molecule is capable of treating the renal injury induced in the test subject, wherein the renal injury inducer is selected from the group consisting of angiotensin II, vasopressin, Sema3a and heparanase.