公开(公告)号：WO2022251948A1

公开(公告)日：2022-12-08

申请号：PCT/CA2022/050334

申请日：2022-03-08

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LIU, Mingyao ,  KESHAVJEE, Shafique ,  CYPEL, Marcelo

IPC: A01N1/02

Abstract: Provided is a lung preservation composition comprising a non-carbonic buffered nutrient media, preferably a phosphate buffered nutrient media, and a dextran, optionally Dextran 40 and and optionally prostaglandin E1 (PGE1), and optionally at least one of alpha 1 antitrypsin (A1AT), an impermeant, optionally raffinose, an antioxidant, optionally glutathione, and necrostatin-1. Also described is a method of preserving a lung prior to and/or during transplant using said lung preservation composition, and kits comprising one or more components of the lung preservation composition.

公开(公告)号：WO2020034043A1

公开(公告)日：2020-02-20

申请号：PCT/CA2019/051121

申请日：2019-08-16

Applicant: THE UNIVERSITY OF BRITISH COLUMBIA ,  UNIVERSITY HEALTH NETWORK

Inventor： CYPEL, Marcelo ,  WANG, Aizhou ,  KESHAVJEE, Shafique ,  WITHERS, Stephen G. ,  RAHFELD, Peter ,  KIZHAKKEDATHU, Jayachandran

IPC: A01N1/02 ,  A61K35/12 ,  C12N9/24 ,  C12P19/00

Abstract: Provided herein are perfusion fluids for enzymatically cleaving A-antigens from a donor organ, and methods, uses, associated therewith. In particular, the perfusion fluids comprise two enzymes, GalNAcDeacetylase and Galactosaminidase and the fluids may further comprise a buffered extracellular solution and/or a crowing agent. Furthermore, the compositions described herein were found to have activity at temperatures and pH levels suitable for cell viability.

公开(公告)号：WO2018184100A1

公开(公告)日：2018-10-11

申请号：PCT/CA2018/050400

申请日：2018-03-29

Applicant: UNIVERSITY HEALTH NETWORK ,  BAGNATO, Vanderlei, Salvador

Inventor： BAGNATO, Vanderlei, Salvador ,  CYPEL, Marcelo ,  KESHAVJEE, Shafique ,  WADDELL, Thomas, Kenneth ,  GALASSO, Marcos, Theophilo

IPC: A61L2/08 ,  A61L2/10 ,  B01L3/00

Abstract: Disclosed are apparatuses and methods for irradiating a perfusate. The apparatus includes a tank which defines a first chamber. A separator is located inside the first chamber. The separator defines a second chamber. The first chamber and the second chamber are concentric and have substantially annular cross sections, each having at least one diameter and a substantially common longitudinal axis. A perfusate is introduced into the first chamber by an inlet. A UV radiation-emitting device is disposed inside the second chamber for providing irradiation to the perfusate. Irradiated perfusate is removed from the tank by an outlet. Other apparatuses and systems are described and methods for inactivating micro organisms by performing EVP and irradiating the perfusate.

公开(公告)号：WO2022226632A1

公开(公告)日：2022-11-03

申请号：PCT/CA2022/050625

申请日：2022-04-22

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KESHAVJEE, Shafique ,  CYPEL, Marcelo ,  LIU, Mingyao ,  JUVET, Stephen ,  MESAKI, Kumi

IPC: C12N15/85 ,  A61K31/7105 ,  A61K35/12 ,  A61K38/46 ,  A61P29/00 ,  A61P37/06 ,  C12N5/10 ,  C12N5/071 ,  C12N15/09 ,  C12N15/12 ,  C12N15/19 ,  C12N15/113

Abstract: The present disclosure relates generally to epigenetically and genetically modified organs and tissues and methods of producing same. In particular, the present disclosure is directed to organs and tissues that have been epigenetically and/or genetically modified at one or multiple loci to control inflammation-regulating or immune-regulating gene expression and thereby improve the condition of the organs and tissues.

公开(公告)号：WO2019023790A1

公开(公告)日：2019-02-07

申请号：PCT/CA2018/050922

申请日：2018-07-30

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KESHAVJEE, Shafique ,  LIU, Mingyao ,  CYPEL, Marcelo ,  SAGE, Andrew

IPC: G01N33/48 ,  A61B5/00 ,  G01N33/53 ,  G01N33/543

Abstract: Methods and kits for screening, diagnosing, detecting or predicting a patient outcome/risk variable for a lung transplant recipient after transplant or an EVLP outcome by measuring biomarker levels of one or more biomarkers selected from IL-6, IL-8, sTNFR1 and sTREM-1 in EVLP perfusate are described. The methods involve for example, i. obtaining one or more test EVLP perfusate samples of a donor lung; ii. determining in one or more test EVLP perfusate sample of a donor lung, a polypeptide level of one or more biomarkers selected from IL-8, IL-6, sTNFR1 and sTREM-1; and iii. a) comparing the polypeptide level of the one or more biomarkers in the perfusate sample with a control or cut-off level, wherein the differential level is indicative of outcome/risk of after transplant or of an EVLP outcome; or b) using the polypeptide level of one or several of the one or more biomarkers in combination, as part of an algebraic calculation of outcome/risk.

公开(公告)号：WO2020118452A1

公开(公告)日：2020-06-18

申请号：PCT/CA2019/051813

申请日：2019-12-13

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KESHAVJEE, Shafique ,  LIU, Mingyao ,  CYPEL, Marcelo ,  SAGE, Andrew

IPC: G01N33/48 ,  G01N33/53 ,  G01N33/543 ,  G06F16/90 ,  G06N20/00

Abstract: Methods and kits for screening, diagnosing, detecting or predicting a patient outcome/risk variable for a lung transplant recipient after transplant or an EVLP outcome by measuring biomarker levels of at least three biomarkers selected from IL-6, IL-8, IL-10 and IL-1β optionally in combination with one or both of sTNFR1 and sTREM1 in EVLP perfusate are described. The methods involve for example, i. obtaining one or more test EVLP perfusate samples of a donor lung; ii. determining in one or more test EVLP perfusate sample of a donor lung, a polypeptide level of the at least three biomarkers selected from IL-8, IL-6, IL-10 and IL-1β and optionally one or both of sTNFR1 and sTREM1 i; and iii. a) comparing the one or more parameter values related to a level of the at least three biomarkers in the perfusate sample with control EVLP data or a cut-off level, wherein the differential level is indicative of outcome/risk of after transplant or of an EVLP outcome; or b) using the one or more parameter values related to a level of the at least three biomarkers in combination, as part of an algebraic calculation or model of outcome/risk.

公开(公告)号：WO2014127463A1

公开(公告)日：2014-08-28

申请号：PCT/CA2014/000139

申请日：2014-02-20

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KESHAVJEE, Shaf ,  LIU, Mingyao ,  CYPEL, Marcelo

IPC: C12Q1/68 ,  G01N33/48 ,  G01N33/53 ,  G06F19/20

CPC classification number: C12Q1/6883 ,  C12Q2600/112 ,  C12Q2600/158 ,  G01N33/6869 ,  G01N2333/4727 ,  G01N2333/5412 ,  G01N2333/5428 ,  G01N2800/245 ,  G01N2800/50

Abstract: Methods for assaying a donor lung for chronic allograft lung dysfunction (CLAD) optionally bronchiolitis obliterans syndrome (BOS) subtype or restrictive allograft syndrome (RAS) subtype of CLAD or risk of developing BOS subtype or RAS subtype CLAD post-transplant, the method comprising: a. measuring a normalized expression level of an RNA transcript of IL-6 or an expression product thereof in a sample of the donor lung pre-transplant or a normalized expression level of one or more S100 protein, optionally S100A8 and/or S100A9, polypeptide expression product in a sample from the donor lung post-transplant; b. assessing the likelihood of the donor lung developing BOS subtype CLAD or RAS subtype CLAD post-transplant based on said IL-6, S100, optionally S100A8 and/or S100A9, expression level wherein IL-6 expression level is positively correlated with an increased likelihood of developing BOS post-transplant, S100A8 expression level is positively correlated with having or having an increased likelihood of developing RAS and/or BOS subtype CLAD, and S100A9 is positively correlated with having and having an increased likelihood of developing RAS subtype CLAD.

Abstract translation: 用于测定供体肺用于慢性同种异体移植肺功能障碍（CLAD）的方法，任选的细支气管闭塞症综合征（BOS）亚型或CLAD的限制性同种异体移植综合征（RAS）亚型或发生移植后BOS亚型或RAS亚型CLAD的风险，所述方法包括： 一个。 测量供体肺移植前样品中IL-6或其表达产物的RNA转录物的标准化表达水平或一种或多种S100蛋白（任选S100A8和/或S100A9）多肽表达产物的标准化表达水平 在供体肺移植后的样品中; 湾 基于所述IL-6，S100，任选的S100A8和/或S100A9，评估供体肺发展BOS亚型CLAD或RAS亚型CLAD的可能性，其中IL-6表达水平与增加的可能性呈正相关 开发BOS移植后，S100A8表达水平与发展RAS和/或BOS亚型CLAD的可能性增加呈正相关，S100A9与具有增加的RAS亚型CLAD的可能性增加呈正相关。

公开(公告)号：WO2014127462A1

公开(公告)日：2014-08-28

申请号：PCT/CA2014/000138

申请日：2014-02-20

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KESHAVJEE, Shaf ,  LIU, Mingyao ,  CYPEL, Marcelo

IPC: G01N33/48 ,  G01N33/483 ,  G01N33/53 ,  G01N33/543

CPC classification number: G01N33/6884 ,  C40B30/02 ,  G01N33/68 ,  G01N2333/5754 ,  G01N2800/245

Abstract: A method of classifying a lung graft subjected to normothermic ex vivo lung perfusion (EVLP), during perfusion and/or after perfusion, the method comprising: a) collecting a test sample from the lung graft; b) measuring a polypeptide level of a negative transplant predictor gene product selected from CCG predictor gene products M-CSF, IL-8 SCGF-beta, GRO-alpha, G-CSF, MIP-1 alpha, and/or MIP-1beta, endothelin predictor gene products endothelin 1 (ET-1) and/or big ET-1, and/or apoptosis predictor gene products cytokeratin 18 (CK-18), caspase 3 and/or HMGB-1 in the sample and/or determining a metabolite profile of the sample for lung grafts that are from donors where the death was due to cardiac death (DCD); c) identifying the graft as a good candidate for transplant or a poor candidate for transplant wherein an increased polypeptide level of one or more negative transplant outcome predictor gene products compared to an outcome control or a reference metabolic profile is indicative the graft is a poor candidate for transplant.

Abstract translation: 一种在灌注和/或灌注后进行正常体温离体肺灌注（EVLP）分类的肺移植物的方法，所述方法包括：a）从肺移植物中收集测试样品; b）测量选自CCG预测基因产物M-CSF，IL-8 SCGF-β，GRO-α，G-CSF，MIP-1α和/或MIP-1beta的阴性移植预测基因产物的多肽水平， 内皮素预测基因产物内皮素1（ET-1）和/或大ET-1和/或凋亡预测基因产物细胞角蛋白18（CK-18），半胱天冬酶3和/或HMGB-1在样品中和/或确定 来自供体的肺移植物的样品的代谢物谱，其中死亡是由于心脏死亡（DCD）; c）将移植物鉴定为移植的良好候选者或用于移植的不良候选者，其中与结果对照或参照代谢特征相比，一种或多种阴性移植结果预测基因产物的多肽水平增加指示移植物是不良候选物 用于移植。

公开(公告)号：WO2023044583A1

公开(公告)日：2023-03-30

申请号：PCT/CA2022/051424

申请日：2022-09-26

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KESHAVJEE, Shafique ,  SAGE, Andrew ,  CYPEL, Marcelo ,  MARTINU, Tereza

IPC: G01N33/50 ,  G01N33/52

Abstract: Methods, kits and devices for assessing bile acid in a donor lung and/or a transplant recipient are described. The methods involve obtaining from the donor lung or transplant recipient a bronchial wash sample, optionally a bronchoalveolar lavage (BAL) sample or a large airway bronchial wash (LABW) sample; measuring in the bronchial wash sample the level of bile acid and optionally one or more inflammation markers, comparing biomarker levels with a control or cut-off level, wherein a differential biomarker level is indicative of an outcome of the donor lung or transplant recipient, including risk of aspiration, suitability of the donor lung, or risk of a particular outcome in the transplant recipient.

公开(公告)号：WO2021179096A

公开(公告)日：2021-09-16

申请号：PCT/CA2021/050343

申请日：2021-03-15

Applicant: UNIVERSITY HEALTH NETWORK [CA]/[CA]

Inventor： SAGE, Andrew ,  VALERO, Jerome ,  DEL SORBO, Lorenzo ,  CYPEL, Marcelo ,  WANG, Bo ,  KESHAVJEE, Shafique

IPC: G01N33/48 ,  G01N33/53 ,  G01N33/543 ,  G16H50/30

Abstract: Methods and kits for screening, diagnosing, detecting or predicting a patient outcome/risk in a patient with a respiratory illness, the method comprising: a. obtaining a sample obtained from the patient; b. quantitatively measuring in the sample a polypeptide level of one or more biomarkers selected from: IL-6, CXCL8, IL-10, IL-1RA, IL-2, IL-4, IL-7, IL-9, IL-13, IL-17, IFN-g, IP-10, MCP-1, G-CSF, GM-CSF, FGF-basic, SCGF-β, GRO-α, MIP1-α, MIP1-β, CK-18, PDGF-bb, caspase 3, HMGB-1, TNF α, VEGF, sTNFR1 and sTREM1; and c. i) comparing the level of the one or more biomarkers in the sample with a control or cut-off level, wherein the differential level is indicative of patient outcome risk; or ii) using the polypeptide level of several of the biomarkers in combination, as inputs for an algebraic calculation or machine learning model of patient outcome risk.