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1. 发明申请

US20080234262A1 PYRAZOLOPYRIMIDINE ANALOGS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS 审中-公开
标题翻译：吡唑并嘧啶类似物及其作为MTOR激酶和PI3激酶抑制剂的用途
公开(公告)号：US20080234262A1
公开(公告)日：2008-09-25
申请号：US12050445
申请日：2008-03-18
申请人： Arie Zask , Pawel Wojciech Nowak , Jeroen Cunera Verheijen , Kevin J. Curran , Joshua Kaplan , David Malwitz , Matthew Gregory Bursavich , Derek Cecil Cole , Semiramis Ayral-Kaloustian , Ker Yu , David James Richard , Mark Lefever
发明人： Arie Zask , Pawel Wojciech Nowak , Jeroen Cunera Verheijen , Kevin J. Curran , Joshua Kaplan , David Malwitz , Matthew Gregory Bursavich , Derek Cecil Cole , Semiramis Ayral-Kaloustian , Ker Yu , David James Richard , Mark Lefever
IPC分类号： A61K31/5377 , A61K31/519 , A61P35/00 , C07D413/14 , C07D487/04
CPC分类号： C07D487/04
摘要： The present invention relates to Pyrazolopyrimidine Analogs, methods of making Pyrazolopyrimidine Analogs, compositions comprising a Pyrazolopyrimidine Analog, and methods for treating mTOR-related disorders comprising administering to a subject in need thereof an effective amount of a Pyrazolopyrimidine Analog. The invention also relates to treating PI3K-related disorders comprising administering to a subject in need thereof an effective amount of a Pyrazolopyrimidine Analog.
摘要翻译：本发明涉及吡唑并嘧啶类似物，制备吡唑并嘧啶类似物的方法，包含吡唑并嘧啶类似物的组合物和用于治疗mTOR相关病症的方法，其包括向有需要的受试者施用有效量的吡唑并嘧啶类似物。本发明还涉及治疗PI3K相关疾病，包括向有需要的受试者施用有效量的吡唑并嘧啶类似物。

2. 发明申请

US20080268462A1 Haptens, hapten conjugates, compositions thereof and method for their preparation and use 有权
标题翻译：半抗原，半抗原共轭物，其组合物及其制备和使用方法
公开(公告)号：US20080268462A1
公开(公告)日：2008-10-30
申请号：US11982627
申请日：2007-11-01
申请人： Jerome W. Kosmeder , Mark Lefever , Donald Johnson , Michael Farrell , Zhanna Zhilina , Christopher Bieniarz
发明人： Jerome W. Kosmeder , Mark Lefever , Donald Johnson , Michael Farrell , Zhanna Zhilina , Christopher Bieniarz
IPC分类号： G01N33/53 , C07K16/44 , C07C205/06 , C07D493/04 , C07H21/04 , C12N9/08 , C07D307/78
CPC分类号： G01N33/5308 , C07D495/04 , C12Q1/6804 , C12Q1/6841 , C12Q1/6886 , G01N33/532 , G01N33/533 , G01N33/58 , G01N33/582 , G01N33/583 , Y10S435/961 , Y10S530/807
摘要： A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.
摘要翻译：描述了用于执行多路诊断测定的方法，例如样品中两种或更多种不同靶标。一个实施方案包括使样品与特异性结合两个或更多个不同靶标的两个或多个特异性结合部分接触。两个或更多个特异性结合部分与不同的半抗原结合，并且至少一个半抗原是恶唑，吡唑，噻唑，除二硝基苯基以外的硝基芳基化合物，苯并呋咱，三萜，脲，硫脲，旋叶，香豆素，环链烷醇，杂二芳基，偶氮芳基或苯并二氮杂。将样品与两种或更多种可分别检测的不同的抗半抗原抗体接触。两种或更多种不同的抗半抗原抗体可以缀合到不同的可检测标记上。

3. 发明申请

US20070117153A1 Molecular conjugate 审中-公开
标题翻译：分子结合物
公开(公告)号：US20070117153A1
公开(公告)日：2007-05-24
申请号：US11603425
申请日：2006-11-21
申请人： Christopher Bieniarz , Julia Ashworth-Sharpe , Casey Kernag , Jerome Kosmeder , Mark Lefever
发明人： Christopher Bieniarz , Julia Ashworth-Sharpe , Casey Kernag , Jerome Kosmeder , Mark Lefever
IPC分类号： G01N33/53 , C07K14/47 , C07C323/39
CPC分类号： G01N33/581 , A61K39/44 , A61K47/6801 , A61K47/6803 , A61K47/6815 , C07C319/02 , C07C323/22 , C07C323/60 , C07C327/28 , C07K16/00 , C12N9/16 , C12N9/96 , C12Y301/03001 , G01N33/532 , G01N33/535 , C07C323/12
摘要： A method is disclosed for making a conjugate of two molecules using a hydrazide thiol linker. In a particular working embodiment, an Fc-specific antibody-enzyme conjugate is made using the method and demonstrated to provide exceptional staining sensitivity and specificity in immunohistochemical and in situ hybridization assays.
摘要翻译：公开了使用酰肼硫醇连接体制备两个分子的缀合物的方法。在特定的工作实施方案中，使用该方法制备Fc特异性抗体 - 酶缀合物，并证实其在免疫组织化学和原位杂交测定中提供特殊的染色敏感性和特异性。

4. 发明申请

US20060246523A1 Antibody conjugates 审中-公开
公开(公告)号：US20060246523A1
公开(公告)日：2006-11-02
申请号：US11413418
申请日：2006-04-27
申请人： Christopher Bieniarz , Jennifer Wong , Mark Lefever , Jerome Kosmeder , Julia Ashworth-Sharpe , Casey Kernag
发明人： Christopher Bieniarz , Jennifer Wong , Mark Lefever , Jerome Kosmeder , Julia Ashworth-Sharpe , Casey Kernag
IPC分类号： G01N33/53 , C12N9/00 , C07K16/18 , C07K16/46
CPC分类号： C12N9/16 , A61K47/65 , A61K47/6815 , C07K16/42 , C07K16/44 , C07K2317/76 , C12N9/0065 , C12N9/96 , G01N33/535
摘要： Antibody/signal-generating moiety conjugates are disclosed that include an antibody covalently linked to a signal-generating moiety through a heterobifunctional polyalkyleneglycol linker. The disclosed conjugates show exceptional signal-generation in immunohistochemical and in situ hybridization assays on tissue sections and cytology samples. In one embodiment, enzyme-metallographic detection of nucleic acid sequences with hapten-labeled probes can be accomplished using the disclosed conjugates as a primary antibody without amplification.

5. 发明授权

US08846320B2 Haptens, hapten conjugates, compositions thereof and method for their preparation and use 有权
标题翻译：半抗原，半抗原共轭物，其组合物及其制备和使用方法
公开(公告)号：US08846320B2
公开(公告)日：2014-09-30
申请号：US12660017
申请日：2010-02-17
申请人： Jerome W. Kosmeder , Mark Lefever , Donald Johnson , Michael Farrell , Zhanna Zhilina , Christopher Bieniarz
发明人： Jerome W. Kosmeder , Mark Lefever , Donald Johnson , Michael Farrell , Zhanna Zhilina , Christopher Bieniarz
IPC分类号： G01N33/53 , G01N33/532 , G01N33/58
CPC分类号： G01N33/5308 , C07D495/04 , C12Q1/6804 , C12Q1/6841 , C12Q1/6886 , G01N33/532 , G01N33/533 , G01N33/58 , G01N33/582 , G01N33/583 , Y10S435/961 , Y10S530/807
摘要： A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.
摘要翻译：描述了用于执行多路诊断测定的方法，例如样品中两种或更多种不同靶标。一个实施方案包括使样品与特异性结合两个或更多个不同靶标的两个或多个特异性结合部分接触。两个或更多个特异性结合部分与不同的半抗原结合，至少一个半抗原是恶唑，吡唑，噻唑，除二硝基苯基以外的硝基芳基化合物，苯并呋咱，三萜烯，脲，硫脲，旋叶，香豆素，环链烷醇，杂二芳基，偶氮芳基或苯并二氮杂。将样品与两种或更多种可分别检测的不同的抗半抗原抗体接触。两种或更多种不同的抗半抗原抗体可以缀合到不同的可检测标记上。

6. 发明申请

US20130109019A1 HAPTEN CONJUGATES FOR TARGET DETECTION 审中-公开
标题翻译：寻找目标检测
公开(公告)号：US20130109019A1
公开(公告)日：2013-05-02
申请号：US13805978
申请日：2011-07-01
申请人： Adrian E. Murillo , Jerome W. Kosmeder , Eric May , William Day , Mark Lefever , Anne M. Pedata , Christopher Bieniarz , Phillip Miller
发明人： Adrian E. Murillo , Jerome W. Kosmeder , Eric May , William Day , Mark Lefever , Anne M. Pedata , Christopher Bieniarz , Phillip Miller
IPC分类号： C07D277/54 , C07C237/20 , C07D271/12 , C07D233/90 , C07D243/00 , C07D241/52
CPC分类号： C07D277/54 , A61K47/51 , C07C235/34 , C07C237/20 , C07C311/37 , C07D233/90 , C07D241/52 , C07D243/00 , C07D271/12 , G01N33/581 , G01N2333/908
摘要： Embodiments of hapten conjugates including a hapten, an optional linker, and a peroxidase-activatable aryl moiety are disclosed. In some embodiments, the peroxidase-activatable aryl moiety is tyramine or a tyramine derivative. Embodiments of methods for making and using the hapten conjugates also are disclosed. In particular embodiments, the hapten conjugates are used in a signal amplification assay. In certain embodiments, the hapten is an oxazole, a pyrazole, a thiazole, a benzofurazan, a triterpene, a urea, a thiourea other than a rhodamine thiourea, a nitroaryl other than dinitrophenyl or trinitrophenyl, a rotenoid, a cyclolignan, a heterobiaryl, an azoaryl, a benzodiazepine, or 7-diethylamino-3-carboxycoumarin. The hapten is coupled to the peroxidase-activatable aryl moiety directly or indirectly via a linker. In certain embodiments, the hapten conjugates are used in multiplexed assays.
摘要翻译：公开了包含半抗原，任选接头和过氧化物酶活化的芳基部分的半抗原共轭物的实施方案。在一些实施方案中，过氧化物酶可活化的芳基部分是酪胺或酪胺衍生物。还公开了制备和使用半抗原共轭物的方法的实施方案。在具体实施方案中，半抗原共轭物用于信号放大测定。在某些实施方案中，半抗原是恶唑，吡唑，噻唑，苯并呋咱，三萜，脲，除罗丹明硫脲以外的硫脲，除二硝基苯基或三硝基苯基以外的硝基芳基，旋环体，环链烷基，异二芳基，偶氮二芳基，苯并二氮杂或7-二乙基氨基-3-羧基香豆素。半抗原通过接头直接或间接地与过氧化物酶活化的芳基部分偶联。在某些实施方案中，半抗原共轭物用于多重测定。

7. 发明授权

US09291597B2 Detecting targets using mass tags and mass spectrometry 有权
标题翻译：使用质量标签和质谱检测目标
公开(公告)号：US09291597B2
公开(公告)日：2016-03-22
申请号：US13805983
申请日：2011-07-01
申请人： Rui Hong , Hong Wang , Mark Lefever , Jan Froehlich , Christopher Bieniarz , Brian Kelly , Phillip Miller
发明人： Rui Hong , Hong Wang , Mark Lefever , Jan Froehlich , Christopher Bieniarz , Brian Kelly , Phillip Miller
IPC分类号： G01N27/62 , G01N33/68
CPC分类号： G01N33/6848 , G01N27/62
摘要： Particular disclosed embodiments disclosed herein concern using a one or more various mass tags, which can be specifically deposited at targets through direct or indirect enzymatic-catalyzed transformation, to provide a method for identifying targets in tissue samples. The mass tags may be labeled with stable isotopes to produce mass tags having the same chemical structure but different masses. Mass codes produced by ionizing the mass tags are detected and/or quantified using mass spectrometry. The method can be used for multiplexed detection of multiple targets in a particular sample. In some embodiments, a map divided into sections representing sections of the tissue sample may be prepared, with the map sections including data corresponding to quantification data wherein the size of a mass peak is determined and correlated with the amount of a target for the corresponding tissue sample section.
摘要翻译：本文公开的具体公开的实施方案涉及使用一种或多种各种质量标签，其可以通过直接或间接的酶催化转化特异性沉积在靶上，以提供用于鉴定组织样品中靶标的方法。质量标签可以用稳定同位素标记，以产生具有相同化学结构但质量不同的质量标签。使用质谱检测和/或定量通过电离质量标签产生的质量代码。该方法可用于特定样品中多个目标的多路检测。在一些实施例中，可以制备分成表示组织样本部分的部分的图，其中，图表部分包括对应于量化数据的数据，其中质量峰的大小被确定并与相应组织的靶的量相关联样品部分。

8. 发明申请

US20100184087A1 Haptens, hapten conjugates, compositions thereof and method for their preparation and use 有权
标题翻译：半抗原，半抗原共轭物，其组合物及其制备和使用方法
公开(公告)号：US20100184087A1
公开(公告)日：2010-07-22
申请号：US12660017
申请日：2010-02-17
申请人： Jerome W. Kosmeder , Mark Lefever , Donald Johnson , Michael Farrell , Zhanna Zhilina , Christopher Bieniarz
发明人： Jerome W. Kosmeder , Mark Lefever , Donald Johnson , Michael Farrell , Zhanna Zhilina , Christopher Bieniarz
IPC分类号： G01N33/53
CPC分类号： G01N33/5308 , C07D495/04 , C12Q1/6804 , C12Q1/6841 , C12Q1/6886 , G01N33/532 , G01N33/533 , G01N33/58 , G01N33/582 , G01N33/583 , Y10S435/961 , Y10S530/807
摘要： A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.
摘要翻译：描述了用于执行多路诊断测定的方法，例如样品中两种或更多种不同靶标。一个实施方案包括使样品与特异性结合两个或更多个不同靶标的两个或多个特异性结合部分接触。两个或更多个特异性结合部分与不同的半抗原结合，至少一个半抗原是恶唑，吡唑，噻唑，除二硝基苯基以外的硝基芳基化合物，苯并呋咱，三萜烯，脲，硫脲，旋叶，香豆素，环链烷醇，杂二芳基，偶氮芳基或苯并二氮杂。将样品与两种或更多种可分别检测的不同的抗半抗原抗体接触。两种或更多种不同的抗半抗原抗体可以缀合到不同的可检测标记上。

9. 发明申请

US20100136652A1 Molecular Conjugate 有权
标题翻译：分子共轭体
公开(公告)号：US20100136652A1
公开(公告)日：2010-06-03
申请号：US12687564
申请日：2010-01-14
申请人： Christopher Bieniarz , Julia Ashworth-Sharpe , Casey A. Kernag , Jerome W. Kosmeder , Mark Lefever
发明人： Christopher Bieniarz , Julia Ashworth-Sharpe , Casey A. Kernag , Jerome W. Kosmeder , Mark Lefever
IPC分类号： C12N9/08 , C07C241/00 , C07K16/00 , C07D249/04 , C12N9/00 , C12N9/18 , C07K16/46
CPC分类号： G01N33/581 , A61K39/44 , A61K47/6801 , A61K47/6803 , A61K47/6815 , C07C319/02 , C07C323/22 , C07C323/60 , C07C327/28 , C07K16/00 , C12N9/16 , C12N9/96 , C12Y301/03001 , G01N33/532 , G01N33/535 , C07C323/12
摘要： A method is disclosed for making a conjugate of two molecules using a hydrazide thiol linker. In a particular working embodiment, an Fc-specific antibody-enzyme conjugate is made using the method and demonstrated to provide exceptional staining sensitivity and specificity in immunohistochemical and in situ hybridization assays.
摘要翻译：公开了使用酰肼硫醇连接体制备两个分子的缀合物的方法。在特定的工作实施方案中，使用该方法制备Fc特异性抗体 - 酶缀合物，并证实其在免疫组织化学和原位杂交测定中提供特殊的染色敏感性和特异性。

10. 发明授权

US08658389B2 Antibody conjugates 有权
标题翻译：抗体缀合物
公开(公告)号：US08658389B2
公开(公告)日：2014-02-25
申请号：US12381638
申请日：2009-03-13
申请人： Christopher Bieniarz , Jennifer Wong , Mark Lefever , Jerome W. Kosmeder, II , Julia Ashworth-Sharpe , Casey A. Kernag
发明人： Christopher Bieniarz , Jennifer Wong , Mark Lefever , Jerome W. Kosmeder, II , Julia Ashworth-Sharpe , Casey A. Kernag
IPC分类号： G01N33/535 , G01N33/53 , G01N33/532 , G01N21/76
CPC分类号： G01N33/535 , A61K47/65 , A61K47/6815 , C07K16/42 , C07K16/44 , C07K2317/76 , C12N9/0065 , C12N9/16 , C12N9/96
摘要： Antibody/signal-generating moiety conjugates are disclosed that include an antibody covalently linked to a signal-generating moiety through a heterobifunctional polyalkyleneglycol linker. The disclosed conjugates show exceptional signal-generation in immunohistochemical and in situ hybridization assays on tissue sections and cytology samples. In one embodiment, enzyme-metallographic detection of nucleic acid sequences with hapten-labeled probes can be accomplished using the disclosed conjugates as a primary antibody without amplification.
摘要翻译：公开了抗体/信号产生部分缀合物，其包括通过异双功能聚亚烷基二醇连接体与产生信号的部分共价连接的抗体。所公开的缀合物在组织切片和细胞学样品的免疫组织化学和原位杂交测定中显示出异常的信号产生。在一个实施方案中，用半抗原标记的探针对核酸序列的酶 - 金相检测可以使用所公开的缀合物作为一级抗体而无需扩增来完成。

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