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Publication Number
US-12216114-B2
Publication Date
2025-02-04
Expiration Date
Abstract
The present invention relates to methods of evaluating and/or treating organs during isolated organ perfusion, and kits for carrying out this evaluation.
Core Innovation
The invention concerns objectively evaluating and treating an isolated organ with existing damage during isolated organ perfusion by measuring biomarker concentrations in the perfusate during perfusing. The method uses a perfusate biomarker concentration of a cell rupture marker to identify the isolated organ as comprising cells that have ruptured, based on comparing the measured concentration to a reference value as the perfusing continues.
The cell rupture marker comprises one or more of double stranded DNA (dsDNA), mitochondrial DNA, or ribosomes. After the isolated organ is identified as comprising cells that have ruptured, the method adds a tissue factor (TF) suppressor molecule to the perfusate only after that identification, and then further perfuses the isolated organ with the perfusate to thereby treat the isolated organ.
In particular embodiments, the TF suppressor molecule comprises a cyclooxygenase (COX) inhibitor. The document describes the use of TF and tPA and rupture markers, including assays for biomarker quantification and biomarker panel approaches, and reports ex vivo human lung datasets showing aggregated cut-off performance, including example reference thresholds and decline versus accepted lungs with correlation to transplant decisions and potential reduction of ischemia reperfusion injury (IRI).
Claims Coverage
The document provides one independent claim (clm-00001). It covers a perfusion workflow with conditional treatment based on a cell rupture marker measured in the perfusate and compared to a reference value, followed by addition of a TF suppressor molecule comprising a COX inhibitor after identification of ruptured cells. Dependent claims refine marker selection, reference-value constraints, measurement timing, and specify TF suppressor molecule details.
Treating isolated organ with existing damage during isolated organ perfusion by perfusate cell rupture marker identification
Perfusing the isolated organ with a perfusate; measuring a concentration of a cell rupture marker in the perfusate during perfusing; comparing the concentration to a reference value of the cell rupture marker as the perfusing continues to identify the isolated organ as comprising cells that have ruptured; and then further perfusing the isolated organ after treatment.
Conditional addition of TF suppressor molecule only after identification of ruptured cells
Adding a tissue factor (TF) suppressor molecule to the perfusate only after having identified the isolated organ as comprising cells that have ruptured; and further perfusing the isolated organ after the TF suppressor molecule has been added to treat the isolated organ.
Rupture marker definition and TF suppressor molecule as a COX inhibitor
Defining the cell rupture marker as comprising one or more of double stranded DNA (dsDNA), mitochondrial DNA, or ribosomes; and defining the TF suppressor molecule as comprising a cyclooxygenase (COX) inhibitor.
Across the independent-claim scope, inventive coverage is centered on using perfusate-based measurement of a cell rupture marker compared to a reference value to identify ruptured cells during isolated organ perfusion, and then adding a TF suppressor molecule only after that identification, where the TF suppressor molecule comprises a COX inhibitor.
Stated Advantages
Enables objective evaluation of an isolated organ during perfusion by identifying isolated organs comprising cells that have ruptured using perfusate biomarker concentration relative to reference/cut-off values.
Supports treatment of the isolated organ with existing damage by adding a TF suppressor molecule after identification of ruptured cells during perfusion.
Reported aggregated performance based on ex vivo human lung datasets for marker cut-offs and correlation to transplant decisions, including potential IRI reduction [as stated].
Documented Applications
Ex vivo human lung evaluation during perfusion, including aggregated cut-off performance analysis comparing declined versus accepted lungs and correlation to transplant decisions, with potential reduction of ischemia reperfusion injury (IRI).
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