公开(公告)号：WO2007137405A1

公开(公告)日：2007-12-06

申请号：PCT/CA2007/000919

申请日：2007-05-25

Applicant: UNIVERSITY HEALTH NETWORK ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY ,  MOUNT SINAI HOSPITAL ,  FISH, Eleanor ,  GALLIGAN, Carole ,  SIMINOVITCH, Kathy ,  PEREZ, Omar ,  KEYSTONE, Edward ,  BYKERK, Vivian

Inventor： FISH, Eleanor ,  GALLIGAN, Carole ,  SIMINOVITCH, Kathy ,  PEREZ, Omar ,  KEYSTONE, Edward ,  BYKERK, Vivian

IPC: C12Q1/68 ,  C12Q1/04 ,  C12Q1/06 ,  G01N33/48

CPC classification number: C12Q1/6883 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5041 ,  G01N33/5091 ,  G01N2333/70503 ,  G01N2333/70589 ,  G01N2333/70596 ,  G01N2333/90245 ,  G01N2800/102 ,  G01N2800/105

Abstract: The invention provides a novel cell that is a precursor of a fibroblast-like synovial cell. The novel cell is a circulating synovial tissue cell that stains positive for collagen, CD34, CD45, prolyl 4-hydroxylase and CD14. The invention also relates to methods of diagnosing or monitoring rheumatoid arthritis and/or osteoarthritis using gene expression profiles, protein expression profiles, and/or protein phosphorylation profiles of different cell types, including the novel precursor, CD3+ cells, synovial tissue fibroblast-like synovial cells and fibrocytes. The invention also includes methods to identify substances to treat or prevent rheumatoid arthritis and/or osteoarthritis.

Abstract translation: 本发明提供了作为成纤维细胞样滑膜细胞的前体的新型细胞。 新型细胞是对胶原，CD34，CD45，脯氨酰4-羟化酶和CD14呈阳性的循环滑膜组织细胞。 本发明还涉及使用基因表达谱，蛋白质表达谱和/或不同细胞类型的蛋白质磷酸化谱（包括新型前体，CD3 +细胞，滑膜组织成纤维细胞样滑膜）来诊断或监测类风湿性关节炎和/或骨关节炎的方法 细胞和纤维细胞。 本发明还包括鉴定用于治疗或预防类风湿性关节炎和/或骨关节炎的物质的方法。

公开(公告)号：WO2007056192A2

公开(公告)日：2007-05-18

申请号：PCT/US2006/043050

申请日：2006-11-02

Applicant: BECKMAN COULTER, INC. ,  NORTHWESTERN UNIVERSITY ,  UNIVERSITY HEALTH NETWORK ,  CASE WESTERN RESERVE UNIVERSITY ,  ALLEGHENY SINGER RESEARCH INSTITUTE ,  GOOLSBY, Charles ,  SHANKEY, Vincent, T. ,  HEDLEY, David ,  JACOBBERGER, James ,  SHACKNEY, Stanley

Inventor： GOOLSBY, Charles ,  SHANKEY, Vincent, T. ,  HEDLEY, David ,  JACOBBERGER, James ,  SHACKNEY, Stanley

IPC: G01N33/574

CPC classification number: G01N33/57426 ,  G01N33/5052 ,  G01N2800/52

Abstract: The present invention is directed to methods for establishing a composite marker profile for a sample derived from an individual suspected having a neoplastic condition. A composite marker profile of the invention allows for identification of prognostically and therapeutically relevant subgroups of neoplastic conditions and prediction of the clinical course of an individual. The methods of the invention provide tools useful in choosing a therapy for an individual afflicted with a neoplastic condition, including methods for assigning a risk group, methods of predicting an increased risk of relapse, methods of predicting an increased risk of developing secondary complications, methods of choosing a therapy for an individual, methods of determining the efficacy of a therapy in an individual, and methods of determining the prognosis for an individual. In particular, the method of the present invention discloses a method for establishing a composite marker profile that can serve as a prognostic indicator to predict whether the course of a neoplastic condition in a individual will be aggressive or indolent, thereby aiding the clinician in managing the patient and evaluating the modality of treatment to be used. In particular embodiments disclosed herein, the methods of the invention are directed to establishing a composite marker profile for a leukemia selected from the group consisting of Chronic Lymphocytic Leukemia (CLL), Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia (CML), and Acute Lymphocytic Leukemia (ALL).

Abstract translation: 本发明涉及用于建立来自疑似患有肿瘤病症的个体的样品的复合标记物谱的方法。 本发明的复合标记物分布允许鉴定预后和治疗相关的肿瘤病症亚组和预测个体的临床过程。 本发明的方法提供了用于选择患有肿瘤病症的个体的治疗的工具，包括分配风险组的方法，预测复发风险增加的方法，预测发生继发性并发症的风险增加的方法，方法 选择个体治疗的方法，确定个体治疗功效的方法以及确定个体预后的方法。 特别地，本发明的方法公开了一种建立复合标记物谱的方法，该方法可用作预后指标以预测个体肿瘤状况是否具有侵略性或惰性，从而有助于临床医师管理 患者和评估使用的治疗方式。 在本文公开的特定实施方案中，本发明的方法涉及建立选自慢性淋巴细胞性白血病（CLL），急性骨髓性白血病（AML），慢性骨髓性白血病（CML）和 急性淋巴细胞性白血病（ALL）。

公开(公告)号：WO2007019678A1

公开(公告)日：2007-02-22

申请号：PCT/CA2006/001321

申请日：2006-08-14

Applicant: UNIVERSITY HEALTH NETWORK ,  LIU, Jiang ,  JOHNSTON, Michael, Richard ,  WU, Xiao, Yu

Inventor： LIU, Jiang ,  JOHNSTON, Michael, Richard ,  WU, Xiao, Yu

IPC: A61L27/54 ,  A61L27/40 ,  A61L27/44 ,  A61L27/56 ,  A61L27/58 ,  A61P35/00 ,  A61K31/704 ,  A61K31/337 ,  A61M31/00 ,  A61L27/26 ,  A61L27/28

CPC classification number: A61L27/58 ,  A61K31/337 ,  A61K31/704 ,  A61L27/52 ,  A61L27/54 ,  A61L31/18 ,  A61L2300/416 ,  A61L2300/604 ,  A61L2300/622 ,  A61L2300/624 ,  A61L2400/12

Abstract: The present invention is directed to an implantable device comprising a biocompatible and biodegradable matrix impregnated with a bioactive complex suitable for selectively targeting the lymphatic system, wherein the bioactive complex comprises one or more particle forming materials and one or more bioactive agents. The invention is further directed to methods of using and the process of preparing, the implantable device.

Abstract translation: 本发明涉及可植入装置，其包括浸渍有适于选择性靶向淋巴系统的生物活性复合物的生物相容性和可生物降解性基质，其中所述生物活性复合物包含一种或多种形成颗粒的物质和一种或多种生物活性剂。 本发明进一步涉及可植入装置的使用方法和制备方法。

公开(公告)号：WO2005049082A2

公开(公告)日：2005-06-02

申请号：PCT/EP2004/014157

申请日：2004-11-19

Applicant: INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE ,  UNIVERSITY HEALTH NETWORK ,  SMADJA, Florence ,  DICK, John, E.

Inventor： SMADJA, Florence ,  DICK, John, E.

IPC: A61K39/395

CPC classification number: C07K16/2884 ,  A61K2039/505 ,  C07K2317/24

Abstract: The present invention provides two chimeric anti-CD44 antibodies comprising specific animo acid sequence, a (Fab')2, Fab, Fab', scFv, Fv or CDRs fragment thereof, in the preparation of a medicament for eradicating pathological stem cells in cancer therapy, and more specifically in acute myeloid leukaemia therapy.

Abstract translation: 本发明提供两种包含特异性animo酸序列的嵌合抗CD44抗体，其Fab（Fab'）2，Fab，Fab'，scFv，Fv或CDRs片段，用于制备用于根除癌症治疗中的病理性干细胞的药物 ，更具体地在急性骨髓性白血病治疗中。

公开(公告)号：WO2004026285A2

公开(公告)日：2004-04-01

申请号：PCT/CA2003/001387

申请日：2003-09-19

Applicant: UNIVERSITY HEALTH NETWORK ,  AMGEN CANADA INC. ,  CRACKOWER, Michael, A. ,  PENNINGER, Josef, M.

Inventor： CRACKOWER, Michael, A. ,  PENNINGER, Josef, M.

IPC: A61K31/00

CPC classification number: C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0375 ,  A61K31/00 ,  A61K31/343 ,  A61K31/352 ,  A61K31/353 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/585 ,  A61K38/45 ,  C12N9/1205 ,  C12N9/16 ,  C12N2800/30

Abstract: The PTEN/PI3K signaling pathway regulates a vast array of fundamental cellular responses. We show that cardiomyocyte-specific inactivation of tumor suppressor PTEN results in hypertrophy, and unexpectedly, a dramatic decrease in cardiac contractility. Analysis of double mutant mice revealed that the cardiac hypertrophy and the contractility defects can be genetically uncoupled. PI3Kγ mediates the alteration in cell size while PI3Kγ acts as a negative regulator of cardiac contractility. Mechanistically, PI3Kγ inhibits cAMP production and hypercontractility can be reverted by blocking cAMP function. These data show that PTEN has an important in vivo role in cardiomyocyte hypertrophy and GPCR signaling and identify a function for the PTEN-PI3Kγ pathway in the modulation of heart muscle contractility.

Abstract translation: PTEN / PI3K信号通路调节大量基础细胞反应。 我们显示肿瘤抑制基因PTEN的心肌细胞特异性失活导致肥大，意外的是心肌收缩力急剧下降。 双突变小鼠的分析显示，心脏肥大和收缩性缺陷可以在遗传上脱离。 PI3Kgamma介导细胞大小的改变，而PI3Kgamma作为心脏收缩力的负调节剂。 机制上，PI3Kgamma抑制cAMP的产生，超负荷可以通过阻断cAMP功能来恢复。 这些数据表明PTEN在心肌细胞肥大和GPCR信号中具有重要的体内作用，并且在调节心肌收缩力中鉴定了PTEN-PI3Kγ通路的功能。

公开(公告)号：WO2003061587A3

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: A61K31/00

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.

公开(公告)号：WO2003043492A1

公开(公告)日：2003-05-30

申请号：PCT/CA2002/001771

申请日：2002-11-20

Applicant: UNIVERSITY HEALTH NETWORK ,  LILGE, Lothar ,  WILSON, Brian, C. ,  SIMICK, Michelle, K. ,  BOYD, Norman, F.

Inventor： LILGE, Lothar ,  WILSON, Brian, C. ,  SIMICK, Michelle, K. ,  BOYD, Norman, F.

IPC: A61B5/00

CPC classification number: A61B5/4312 ,  A61B5/0091

Abstract: The present invention uses spectroscopic tissue volume measurements using non-ionizing radiation to detect pre-disease transformations in the tissue, which increase the risk for this disease in mammals. The method illuminating a volume of selected tissue of a mammal with light having wavelengths covering a pre-selected spectral range, detecting light transmitted through, or reflected from, volume of selected tissue, and obtaining a spectrum of the detected light. The spectrum of detected light is then represented by one or more basis spectral components, an error term, and an associated scalar coefficient for each of the basis spectral components. The associated scalar coefficient is calculated by minimizing the error term. The associated scalar coefficient of the each of the basis spectral components is correlated with a pre-selected property of the selected tissue known to be indicative of susceptibility of the tissue for the pre-selected disease to obtain the susceptibility for the mammal to developing the pre-selected disease.

Abstract translation: 本发明使用非电离辐射的光谱组织体积测量来检测组织中的疾病前变化，这增加了哺乳动物中该疾病的风险。 所述方法用具有覆盖预选光谱范围的波长的光照射哺乳动物的体积的选定组织，检测透射通过选定组织的体积或从所选择的组织的体积反射的光，并获得检测到的光的光谱。 然后，检测到的光谱由一个或多个基础光谱分量，误差项和每个基本光谱分量的相关标量系数表示。 通过最小化误差项来计算相关联的标量系数。 每个基础光谱分量的相关联的标量系数与所选择的组织的预先选择的性质相关联，所述组织已知指示预先选择的疾病的组织的易感性，以获得哺乳动物开发前体的易感性 选择性疾病

公开(公告)号：WO2002081660A1

公开(公告)日：2002-10-17

申请号：PCT/CA2002/000486

申请日：2002-04-03

Applicant: UNIVERSITY HEALTH NETWORK ,  ERWIN, W., Mark ,  SALO, Paul, T. ,  INMAN, Robert

Inventor： ERWIN, W., Mark ,  SALO, Paul, T. ,  INMAN, Robert

IPC: C12N5/00

CPC classification number: C12N5/0655 ,  A61K35/30 ,  A61K35/32 ,  C07K14/4725 ,  C12N2502/08 ,  C12N2502/1317

Abstract: The present invention provides compositions comprising notochord enriched media and/or one or more factors derived therefrom. Such compositions are useful for enhancing the production of proteoglycan in cells or animals in need thereof, for example for treating degenerative disc disease. The notochord enriched media is preferably obtained from a nonchondrodystrophic animal.

Abstract translation: 本发明提供了包含富含箭头的培养基和/或从其衍生的一个或多个因素的组合物。 这样的组合物可用于增强有需要的细胞或动物中蛋白多糖的产生，例如用于治疗退行性椎间盘疾病。 富含脊髓的培养基优选从非软骨营养不良动物获得。

公开(公告)号：WO2023067577A1

公开(公告)日：2023-04-27

申请号：PCT/IB2022/060159

申请日：2022-10-21

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： HIRANO, Naoto ,  MURATA, Kenji ,  LY, Dalam ,  SAIJO, Hiroshi ,  MATSUNAGA, Yukiko

IPC: C07K14/74 ,  A61K31/7088 ,  A61K38/17 ,  A61K38/46 ,  A61P35/00 ,  A61P37/02 ,  C12N15/10 ,  C12N15/12

Abstract: The present disclosure is directed to methods of modifying an HLA-binding pocket in an HLA molecule in a subject. Some aspects are directed to HLA molecules comprising a modified HLA-binding pocket, where the HLA molecule has increased affinity for a peptide, e.g., an antigen. Other aspects are directed to compositions comprising the same and methods of using the same.

公开(公告)号：WO2022259225A1

公开(公告)日：2022-12-15

申请号：PCT/IB2022/055425

申请日：2022-06-10

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： KELLER, Gordon M. ,  YANG, Donghe

IPC: C12N5/077 ,  A61K35/34 ,  A61P9/00 ,  C12N5/073 ,  C12Q1/02

Abstract: Cardiomyocyte subtypes, including first heart field (FHF) and second heart field(SHF) (e.g., anterior second heart field (aSHF) and posterior second heart field (pSHF)) cells,and methods of making and using such cells, are described.