# US 12,216,114 B2 · Isolated organ evaluation and treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,216,114 B2 - Document ID: US12216114B2 - Status: Granted - Kind: B2 - Application number: 17/150,202 - Filed: 2021-01-15 - Published: 2021-05-06 - Granted: 2025-02-04 - Earliest claimed: 2015-06-25 - Assignees: Xvivo Perfusion AB - Applicants: XVIVO Perfusion AB - Inventors: Magnus Nilsson; Anne-Li Sigvardsson - Web page: https://patentgrep.com/patent/US12216114B2 ## CPC - G01N 33/5082: {Supracellular entities, e.g. tissue, organisms} - A01N 1/122: Preservation or perfusion media - A01N 1/126: Physiologically active agents, e.g. antioxidants or nutrients - G01N 33/6893: {related to diseases not provided for elsewhere} - 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) - A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS ## Abstract The present invention relates to methods of evaluating and/or treating organs during isolated organ perfusion, and kits for carrying out this evaluation. ## Claims ### Claim 1 A method of treating an isolated organ with existing damage during isolated organ perfusion, wherein the isolated organ is determined during the method to be an isolated organ with existing damage based on comprising cells that have ruptured, the method comprising steps of: perfusing the isolated organ with a perfusate; measuring a concentration of a cell rupture marker in the perfusate during the perfusing of the isolated organ; comparing the concentration of the cell rupture marker in the perfusate to a reference value of the cell rupture marker, as the perfusing of the isolated organ continues, to identify the isolated organ as comprising cells that have ruptured; adding a tissue factor (TF) suppressor molecule to the perfusate, as the perfusing of the isolated organ continues, only after having identified the isolated organ as comprising cells that have ruptured; and further perfusing the isolated organ with the perfusate after the TF suppressor molecule has been added, thereby treating the isolated organ, wherein the cell rupture marker comprises one or more of double stranded DNA (dsDNA), mitochondrial DNA, or ribosomes; and the TF suppressor molecule comprises a cyclooxygenase (COX) inhibitor. ### Claim 2 (depends on 1) The method according to claim 1, wherein the COX inhibitor comprises one or more of aspirin, naproxen, ibuprofen, or their equivalents. ### Claim 3 (depends on 2) The method according to claim 2, wherein the COX inhibitor comprises aspirin. ### Claim 4 (depends on 1) The method according to claim 1, wherein the step of adding the TF suppressor molecule to the perfusate as the perfusing of the isolated organ continues comprises adding the COX inhibitor to the perfusate to a concentration of 1 mg/L to 10 g/L. ### Claim 5 (depends on 1) The method according to claim 1, wherein the isolated organ is from an animal or a human being and is a lung or lungs, a kidney, a liver, a heart, a pancreas or a bowel. ### Claim 6 (depends on 1) The method according to claim 1, wherein the isolated organ is circulatorily isolated in vivo or is circulatorily isolated ex vivo. ### Claim 7 (depends on 1) The method according to claim 1, further comprising, after the step of comparing the concentration of the cell rupture marker in the perfusate to the reference value of the cell rupture marker to identify the isolated organ as comprising cells that have ruptured, a step of adding an anti-apoptotic agent to the perfusate. ### Claim 8 (depends on 7) The method according to claim 7, wherein the anti-apoptotic agent comprises one or more inhibitors of c-Myc, Bax, p53, tBid, BCL, or caspase. ### Claim 9 (depends on 1) The method according to claim 1, further comprising, after the step of comparing the concentration of the cell rupture marker in the perfusate to the reference value of the cell rupture marker to identify the isolated organ as comprising cells that have ruptured, a step of adding a fibrinolytic agent to the perfusate. ### Claim 10 (depends on 9) The method according to claim 9, wherein the fibrinolytic agent comprises one or more of Streptokinase or tPA. ### Claim 11 (depends on 1) The method according to claim 1, wherein the reference value of the cell rupture marker is at least 2,000 ng of the cell rupture marker per ml of the perfusate. ### Claim 12 (depends on 1) The method according to claim 1, wherein the cell rupture marker comprises dsDNA, the concentration of the cell rupture marker in the perfusate comprises a concentration of the dsDNA in the perfusate, and the reference value of the cell rupture marker comprises a reference value of dsDNA. ### Claim 13 (depends on 12) The method according to claim 12, wherein the reference value of dsDNA is at least 2,000 ng of dsDNA per ml of the perfusate. ### Claim 14 (depends on 1) The method according to claim 1, wherein the step of measuring the concentration of the cell rupture marker in the perfusate is conducted continuously over a predetermined time period or repeatedly at predetermined intervals. ### Claim 15 (depends on 1) The method according to claim 1, further comprising, after the step of perfusing the isolated organ with a perfusate, a step of measuring a concentration of one or more of TF, tPA, SpA, or SpD in the perfusate. ### Claim 16 (depends on 1) The method according to claim 1, wherein the isolated organ had been under stress in a donor of the isolated organ. ### Claim 17 (depends on 1) The method according to claim 1, wherein the isolated organ is from a donor who had experienced systemic effects of brain death or circulatory arrest.