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1. 发明申请

WO2015119962A1 2,7-DISUBSTITUTED CEPHALOSPORIN DERIVATIVES AS BETA-LACTAMASE SUBSTRATES AND METHODS FOR THEIR USE FOR THE DIAGNOSIS OF TUBERCULOSIS 审中-公开
标题翻译： 2,7-取代的CEPHOROSPORIN衍生物作为β-乳酸酶底物及其用于诊断结核病的方法
公开(公告)号：WO2015119962A1
公开(公告)日：2015-08-13
申请号：PCT/US2015/014295
申请日：2015-02-03
申请人： THE TEXAS A&M UNIVERSITY SYSTEM , THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
发明人： CIRILLO, Jeffrey, D. , RAO, Jianghong , CHENG, Yunfeng , XIE, Hexin
IPC分类号： C07D501/60
CPC分类号： C09B11/24 , C07D501/52 , C07D501/62 , C09B57/02 , C12Q1/04 , C12Q1/18 , C12Q1/34 , G01N2333/30 , G01N2333/986 , G01N2800/12 , G01N2800/52
摘要： Beta-Lactamase substrates and methods for using the substrates to detect beta-lactamase and to diagnose tuberculosis. In the method, a sample is contacted with a compound of the invention, and an optical signal generated from contacting the sample with the compound is measured. In another embodiment, the invention provides a method for diagnosing tuberculosis. In the method, a sample is contacted with a compound of the invention, and an optical signal generated from contacting the sample with the compound is measured. In the methods, the sample may be sputum, pleural fluid, spinal fluid, blood, urine, saliva, stool, tissue biopsies, tissue homogenates, directly in live animals or human patients, or a sample obtained by swabbing an area of interest on a subject.
摘要翻译： β-内酰胺酶底物和使用底物检测β-内酰胺酶和诊断结核病的方法。在该方法中，将样品与本发明的化合物接触，并且测量从样品与化合物接触产生的光学信号。在另一个实施方案中，本发明提供了用于诊断结核病的方法。在该方法中，将样品与本发明的化合物接触，并且测量从样品与化合物接触产生的光学信号。在该方法中，样品可以是直接在活的动物或人类患者中的痰液，胸膜液，脊髓液，血液，尿液，唾液，粪便，组织活组织检查，组织匀浆，或通过在学科。

2. 发明申请

WO2011152883A2 USE OF BACTERIAL BETA-LACTAMASE FOR IN VITRO DIAGNOSTICS AND IN VIVO IMAGING, DIAGNOSTICS AND THERAPEUTICS 审中-公开
标题翻译：用于体外诊断和体内成像，诊断和治疗的细菌β-乳糖酶的使用
公开(公告)号：WO2011152883A2
公开(公告)日：2011-12-08
申请号：PCT/US2011/001018
申请日：2011-06-03
申请人： THE TEXAS A&M UNIVERSITY SYSTEM , THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , CIRILLO, Jeffrey, D. , SACHETTINI, James, C. , RAO, Jianghong , XIE, Hexin
发明人： CIRILLO, Jeffrey, D. , SACHETTINI, James, C. , RAO, Jianghong , XIE, Hexin
IPC分类号： C12Q1/34 , C12Q1/04 , G01N33/52 , G01N33/15 , C12R1/32
CPC分类号： A61K49/0013 , A61K49/0021 , A61K49/0028 , A61K49/0032 , A61K49/0041 , A61K49/0052 , C12Q1/04 , C12Q1/34 , G01N2333/986
摘要： Provided herein are methods for detecting, quantifying, differentiating, diagnosing and imaging pathogenic bacteria or condition associated therewith using substrates for bacterial enzymes. Fluorescent, luminescent or colorimetric signals emitted by substrates or enzyme products in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring a signal emitted from the substrates or products in the presence and absence of the potential therapeutic agent and a diagnostic method for detecting a mycobacterial infection in a subject by contacting biological samples with a substrate and imaging for signals emitted from a mycobacterial beta-lactamase product. Also provided are fluorogenic substrates or substrates comprising a colored dye or a chemical reagent effective to induce a color or pH change.
摘要翻译：本文提供了用于细菌酶底物检测，定量，鉴别，诊断和成像病原菌或与其相关的病症的方法。在细菌存在下由底物或酶产物发射的荧光，发光或比色信号与对照相比较以检测和定位病原菌。本发明提供了一种用于筛选治疗剂以治疗病理生理状况的方法，该方法是通过在存在和不存在潜在治疗剂的情况下测量从底物或产物发出的信号，以及用于通过使生物样品与生物样品接触来检测受试者中的分枝杆菌感染的诊断方法底物和成像从分枝杆菌β-内酰胺酶产物发射的信号。还提供了含有色素或有效诱导颜色或pH变化的化学试剂的荧光底物或底物。

3. 发明公开

EP2318834A2 USE OF BACTERIAL BETA-LACTAMASE FOR IN VITRO DIAGNOSTICS AND IN VIVO IMAGING, DIAGNOSTICS AND THERAPEUTICS 审中-公开
标题翻译：使用细菌β-内酰胺酶用于体外诊断和体内成像，诊断和治疗
公开(公告)号：EP2318834A2
公开(公告)日：2011-05-11
申请号：EP09805273.1
申请日：2009-08-06
申请人： The Texas A&M University System , The Board of Trustees of The Leland Stanford Junior University
发明人： CIRILLO, Jeffrey, D. , RAO, Jianghong
IPC分类号： G01N33/52 , C12Q1/25 , G01N33/569
CPC分类号： C12Q1/04 , A61K49/0013 , C12Q1/34 , G01N2333/986
摘要： Provided herein are imaging methods for detecting, diagnosing and imaging pathogenic bacteria or a pathophysiological condition associated therewith using fluorescent, luminescent or colorimetric detection agents, e.g., fluorogenic substrates for bacterial enzymes, caged luciferins and fluorescent proteins, luciferases and enzymes expressed by recombinant bacteria. Signals emitted by the fluorescent, luminescent or colorimetric detection agents in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Also provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring fluorescence or luminescence emitted from the detection agents in the presence and absence of the potential therapeutic agent. In addition, a method for detecting a pathogenic bacteria via PET or SPECT imaging using a positron-emitting or gamma-emitting substrate for a beta-lactamase or other enzyme or protein of the pathogenic bacteria. Further provided are the fluorogenic substrates CNIR-7 or CNIR7-TAT or the radiolabeled substrates.

4. 发明公开

EP2585611A2 USE OF BACTERIAL BETA-LACTAMASE FOR IN VITRO DIAGNOSTICS AND IN VIVO IMAGING, DIAGNOSTICS AND THERAPEUTICS 审中-公开
标题翻译：使用细菌β-内酰胺酶用于体外诊断和体内成像，诊断和治疗
公开(公告)号：EP2585611A2
公开(公告)日：2013-05-01
申请号：EP11790116.5
申请日：2011-06-03
申请人： The Texas A&M University System , The Board of Trustees of the Leland Stanford Junior University
发明人： CIRILLO, Jeffrey, D. , SACHETTINI, James, C. , RAO, Jianghong , XIE, Hexin
IPC分类号： C12Q1/34 , C12Q1/04 , G01N33/52 , G01N33/15 , C12R1/32
CPC分类号： A61K49/0013 , A61K49/0021 , A61K49/0028 , A61K49/0032 , A61K49/0041 , A61K49/0052 , C12Q1/04 , C12Q1/34 , G01N2333/986
摘要： Provided herein are imaging methods for detecting, diagnosing and imaging pathogenic bacteria or a pathophysiological condition associated therewith using fluorogenic substrates for bacterial enzymes. Fluorescent, luminescent or colorimetric signals emitted by substrates or enzyme products in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring a signal emitted from the fluorogenic substrates or products in the presence and absence of the potential therapeutic agent. In addition, a diagnostic method for detecting a mycobacterial infection in a subject by contacting biological samples with a fluorogenic substrate and imaging for signals emitted from a mycobacterial beta-lactamase product. Provided are fluorogenic substrates CC1, CC2, CHPQ, CR2, CNIR1, CNIR2, CNIR3, CNIR4, CNIR5, CNIR5-QSY22, CNIR7, CNIR9, CNIR10, CNIR-TAT, CDC-1, CDC-2, CDC-3, CDC-4, CDC-5, XHX2-81, XHX2-91, XHX3-26, or XHX3-32 or a derivative thereof.

5. 发明公开

EP3102583A1 2,7-DISUBSTITUTED CEPHALOSPORIN DERIVATIVES AS BETA-LACTAMASE SUBSTRATES AND METHODS FOR THEIR USE FOR THE DIAGNOSIS OF TUBERCULOSIS 有权转让
标题翻译： 2.7二取代头孢ALSβ-内酰胺酶的底物和使用方法结核的诊断
公开(公告)号：EP3102583A1
公开(公告)日：2016-12-14
申请号：EP15746117.9
申请日：2015-02-03
申请人： The Texas A&M University System , The Board of Trustees of the Leland Stanford Junior University
发明人： RAO, Jianghong , XIE, Hexin , CHENG, Yunfeng , CIRILLO, Jeffrey, D.
IPC分类号： C07D501/60
CPC分类号： C09B11/24 , C07D501/52 , C07D501/62 , C09B57/02 , C12Q1/04 , C12Q1/18 , C12Q1/34 , G01N2333/30 , G01N2333/986 , G01N2800/12 , G01N2800/52
摘要： β-Lactamase substrates and methods for using the substrates to detect β-lactamase and to diagnose tuberculosis.
摘要翻译： β-内酰胺酶底物和使用该基板，以检测β-内酰胺酶和诊断结核病的方法。

6. 发明申请

WO2014121217A2 LOCALIZED FLUORESCENCE EXCITATION IN WHOLE BODY OPTICAL IMAGING 审中-公开
标题翻译：全身光学成像中的局部荧光激发
公开(公告)号：WO2014121217A2
公开(公告)日：2014-08-07
申请号：PCT/US2014/014486
申请日：2014-02-03
申请人： THE TEXAS A&M UNIVERSITY SYSTEM
发明人： MAITLAND, Kristin, Carlson , CIRILLO, Jeffrey, D. , KONG, Ying , BIXLER, Joel, N.
CPC分类号： A61B5/0071 , A61B5/0084 , A61B5/4842 , A61B5/4848
摘要： Methods and systems for whole body optical imaging using localized fluorescence excitation.
摘要翻译：使用局部荧光激发的全身光学成像的方法和系统。

7. 发明申请

WO2013173519A1 BETA-LACTAMASE SUBSTRATES AND METHODS OF THEIR USE FOR THE DIAGNOSIS OF TUBERCULOSIS 审中-公开
标题翻译： BETA-LACTAMASE底物及其用于诊断结核病的方法
公开(公告)号：WO2013173519A1
公开(公告)日：2013-11-21
申请号：PCT/US2013/041244
申请日：2013-05-15
申请人： THE TEXAS A&M UNIVERSITY SYSTEM , RAO, Jianghong , XIE, Hexin
发明人： RAO, Jianghong , XIE, Hexin , CIRILLO, Jeffrey, D. , SACCHETTINI, James, C.
IPC分类号： C07D501/22 , A61K31/546 , A61P31/06
CPC分类号： C12Q1/34 , C07D501/24 , C07D501/26 , C07D501/30 , C07D501/34 , C07D501/57 , G01N2333/986 , G01N2800/26
摘要： β-Lactamase substrates and methods for using the substrates to detect β-lactamase diagnose tuberculosis.
摘要翻译： β-内酰胺酶底物和使用底物检测β-内酰胺酶诊断结核病的方法。

8. 发明申请

WO2010016911A2 USE OF BACTERIAL BETA-LACTAMASE FOR IN VITRO DIAGNOSTICS AND IN VIVO IMAGING, DIAGNOSTICS AND THERAPEUTICS 审中-公开
标题翻译：细菌内切β-葡聚糖酶用于体外诊断和体内成像，诊断和治疗
公开(公告)号：WO2010016911A2
公开(公告)日：2010-02-11
申请号：PCT/US2009/004503
申请日：2009-08-06
申请人： THE TEXAS A & M UNIVERSITY SYSTEM
发明人： CIRILLO, Jeffrey, D. , RAO, Jianghong
IPC分类号： G01N33/52 , C12Q1/25 , G01N33/569
CPC分类号： C12Q1/04 , A61K49/0013 , C12Q1/34 , G01N2333/986
摘要： Provided herein are imaging methods for detecting, diagnosing and imaging pathogenic bacteria or a pathophysiological condition associated therewith using fluorescent, luminescent or colorimetric detection agents, e.g., fluorogenic substrates for bacterial enzymes, caged luciferins and fluorescent proteins, luciferases and enzymes expressed by recombinant bacteria. Signals emitted by the fluorescent, luminescent or colorimetric detection agents in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Also provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring fluorescence or luminescence emitted from the detection agents in the presence and absence of the potential therapeutic agent. In addition, a method for detecting a pathogenic bacteria via PET or SPECT imaging using a positron-emitting or gamma-emitting substrate for a beta-lactamase or other enzyme or protein of the pathogenic bacteria. Further provided are the fluorogenic substrates CNIR-7 or CNIR7-TAT or the radiolabeled substrates.
摘要翻译：本文提供了使用荧光，发光或比色检测剂（例如细菌酶的荧光底物，笼状荧光素和荧光蛋白）检测，诊断和成像致病细菌或与其相关的病理生理状况的成像方法，萤光素酶和由重组细菌表达的酶。比较荧光，发光或比色检测剂在细菌存在下发出的信号与对照以检测和定位致病细菌。还提供了筛选治疗剂以通过在存在和不存在潜在治疗剂的情况下测量由检测剂发出的荧光或发光来治疗病理生理状况的方法。此外，还提出了一种使用用于β-内酰胺酶或致病菌的其他酶或蛋白质的正电子发射或γ发射底物通过PET或SPECT成像检测致病细菌的方法。还提供了荧光底物CNIR-7或CNIR7-TAT或放射性标记的底物。

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