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：WO2003061587A2

公开(公告)日：2003-07-31

申请号：PCT/US2003/001726

申请日：2003-01-21

Applicant: GENZYME CORPORATION ,  UNIVERSITY HEALTH NETWORK ,  KESHAVJEE, Shaf ,  ST. GEORGE, Judith, A. ,  LIU, Mingyao

Inventor： KESHAVJEE, Shaf ,  ST. GEORGE, Judith, A. ,  LIU, Mingyao

IPC: A61K

CPC classification number: C07K14/71 ,  A61K31/00 ,  A61K31/194 ,  A61K31/7004 ,  A61K38/00 ,  A61K48/00 ,  A61K2039/505 ,  C07K14/495 ,  C12N2799/022

Abstract: Effective use of a TGF-β antagonist to treat or to prevent loss of transplant function is described herein. Use of a TGF-β antagonist is demonstrated to effectively prevent loss of organ function in a host due to chronic rejection in which TGF-β-mediated fibroproliferation is a characteristic. Expression in situ of a TGF-β antagonist in the form of a recombinant receptor, i.e., TGF-β type III receptor (TGFBIIIR) showed prevention of bronchiolitis obliterans in comparison to untreated controls in a rat lung transplant model. This provides an effective method for preventing or inhibiting chronic rejection of transplant organs such as lung, kidney, liver and hear in vertebrate hosts including human hosts.

Abstract translation: 有效利用TGF- 本文描述了治疗或预防移植功能丧失的拮抗剂。 使用TGF- 拮抗剂被证明能有效地防止由于慢性排斥反应导致宿主中器官功能的丧失，其中TGF-βB介导的纤维增生是一个特征。 TGF-βb原位表达 拮抗剂，其为重组受体的形式，即TGF- III型受体（TGFBIIIR）显示与大鼠肺移植模型中的未处理对照相比，预防闭塞性细支气管炎。 这提供了用于预防或抑制移植器官如肺，肾，肝脏的慢性排斥并在包括人宿主在内的脊椎动物宿主中听到的有效方法。

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：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：WO2017063074A1

公开(公告)日：2017-04-20

申请号：PCT/CA2016/000259

申请日：2016-10-14

Applicant: UNIVERSITY HEALTH NETWORK (UHN) ,  THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO

Inventor： KESHAVJEE, Shaf ,  LIU, Mingyao ,  SAGE, Andrew ,  SARGENT, Edward ,  KELLEY, Shana

IPC: G01N27/416 ,  G01N27/327 ,  G01N33/543 ,  G01N27/30

CPC classification number: G01N33/5438 ,  B82Y30/00 ,  G01N27/3276 ,  G01N27/3278

Abstract: There is described herein a method for the electrochemical quantification of a protein analyte in sample, comprising: providing one or more electrode(s), each comprising at least one peptide attached to its surface, the peptide being the protein or a fragment thereof; contacting the sample and electrode with an antibody in the presence of a redox reporter, wherein the antibody is capable of binding to each of the protein analyte and the peptide on the electrode; measuring an electrochemical signal generated by the redox reporter when a potential is applied; quantifying the protein analyte by comparing the electrochemical signal generated with a control, wherein the electrochemical signal is indirectly proportional to the amount of protein analyte in the sample.

Abstract translation: 本文描述了用于样品中蛋白质分析物的电化学定量的方法，其包括：提供一个或多个电极，每个电极包含至少一个连接至其表面的肽，所述肽为 该蛋白质或其片段; 在氧化还原报道分子存在下使样品和电极与抗体接触，其中所述抗体能够与电极上的每种蛋白质分析物和肽结合; 测量当施加电位时由氧化还原报道分子产生的电化学信号; 通过比较用对照产生的电化学信号来量化蛋白质分析物，其中电化学信号与样品中蛋白质分析物的量间接成比例。

公开(公告)号：WO2021198865A1

公开(公告)日：2021-10-07

申请号：PCT/IB2021/052546

申请日：2021-03-26

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LIU, Mingyao ,  KESHAVJEE, Shafique

IPC: A01N1/02 ,  A61M1/14

Abstract: An organ perfusion solution includes a colloid component, a salt mixture, a buffer system, and a glutamine compound in a physiologically acceptable medium.

公开(公告)号：WO2012109732A1

公开(公告)日：2012-08-23

申请号：PCT/CA2012/000124

申请日：2012-02-16

Applicant: UNIVERSITY HEALTH NETWORK ,  LIU, Mingyao ,  FUNG, Shan-Yu ,  KESHAVJEE, Shaf

Inventor： LIU, Mingyao ,  FUNG, Shan-Yu ,  KESHAVJEE, Shaf

IPC: A61K47/42 ,  A61K31/519 ,  A61K47/18

CPC classification number: A61K31/519 ,  A61K9/0019 ,  A61K9/0073 ,  A61K9/10 ,  A61K47/183 ,  A61K47/42

Abstract: The present disclosure relates to 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine ("PP1") or (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine ("PP2") drug vehicles comprising a self-assembling peptide in combination with a single amino acid, pharmaceutical compositions comprising PP1 or PP2 and the vehicle and methods and uses thereof.

Abstract translation: 本公开涉及4-氨基-5-（4-甲基苯基）-7-（叔丁基）吡唑并[3,4-d] - 嘧啶（“PP1”）或（4-氨基-5-（4- 氯苯基）-7-（叔丁基）吡唑并[3,4-d]嘧啶（“PP2”）药物载体，其包含与单一氨基酸组合的自组装肽，包含PP1或PP2的药物组合物， 方法和用途。