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公开(公告)号：US20090176253A1
公开(公告)日：2009-07-09
申请号：US12381638
申请日：2009-03-13
申请人： Christopher Bieniarz , Jennifer Wong , Mark Lefever , Jerome W. Kosmeder , Julia Ashworth-Sharpe , Casey A. Kernag
发明人： Christopher Bieniarz , Jennifer Wong , Mark Lefever , Jerome W. Kosmeder , Julia Ashworth-Sharpe , Casey A. Kernag
IPC分类号： G01N33/542 , G01N33/53
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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公开(公告)号：US08686122B2
公开(公告)日：2014-04-01
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： C07K1/13 , C07K1/10 , G01N33/532
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。
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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。
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4.发明申请Antibody-Nanoparticle Conjugates and Methods for Making and Using Such Conjugates 有权抗体纳米颗粒结合体及其制备和使用方法公开(公告)号：US20130034854A1
公开(公告)日：2013-02-07
申请号：US13640944
申请日：2011-04-27
申请人： Julia Ashworth-Sharpe , Chol Steven Yun , Zhanna Zhilina , Adrian E. Murillo , Donald D. Johnson , Michael Farrell , Jerome W. Kosmeder , Christopher Bieniarz
发明人： Julia Ashworth-Sharpe , Chol Steven Yun , Zhanna Zhilina , Adrian E. Murillo , Donald D. Johnson , Michael Farrell , Jerome W. Kosmeder , Christopher Bieniarz
IPC分类号： C07K17/14 , G01N33/566 , G01N33/573 , G01N33/553 , C12Q1/68 , B82Y5/00
CPC分类号： G01N33/54346 , C07F9/12 , C07F9/5004 , C07F9/5022 , C07F9/5045 , C07F9/5728 , C07F9/65515 , C07F9/65517 , C07F9/65522 , G01N33/531 , G01N33/553 , G01N33/587 , G01N33/6854 , G01N2333/916
摘要： Disclosed herein are antibody-nanoparticle conjugates that include two or more nanoparticles (such as gold, palladium, platinum, silver, copper, nickel, cobalt, iridium, or an alloy of two or more thereof) directly linked to an antibody or fragment thereof through a metal-thiol bond. Methods of making the antibody-nanoparticle conjugates disclosed herein include reacting an arylphosphine-nanoparticle composite with a reduced antibody to produce an antibody-nanoparticle conjugate. Also disclosed herein are methods for detecting a target molecule in a sample that include using an antibody-nanoparticle conjugate (such as the antibody-nanoparticle conjugates described herein) and kits for detecting target molecules utilizing the methods disclosed herein.
摘要翻译： 本文公开了抗体 - 纳米颗粒缀合物，其包括直接连接到抗体或其片段的两个或更多个纳米颗粒（例如金，钯，铂，银，铜，镍，钴，铱或其两种或多种的合金） 金属硫醇键。 制备本文公开的抗体 - 纳米颗粒缀合物的方法包括使芳基膦 - 纳米颗粒复合物与还原抗体反应以产生抗体 - 纳米颗粒缀合物。 本文还公开了用于检测样品中靶分子的方法，其包括使用抗体 - 纳米颗粒缀合物（例如本文所述的抗体 - 纳米颗粒缀合物）和利用本文公开的方法检测靶分子的试剂盒。
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5.发明授权Antibody-nanoparticle conjugates and methods for making and using such conjugates 有权抗体 - 纳米颗粒缀合物和制备和使用这种缀合物的方法公开(公告)号：US09040310B2
公开(公告)日：2015-05-26
申请号：US13640944
申请日：2011-04-27
申请人： Julia Ashworth-Sharpe , Chol Steven Yun , Zhanna Zhilina , Adrian E. Murillo , Donald D. Johnson , Michael Farrell , Jerome W. Kosmeder , Christopher Bieniarz
发明人： Julia Ashworth-Sharpe , Chol Steven Yun , Zhanna Zhilina , Adrian E. Murillo , Donald D. Johnson , Michael Farrell , Jerome W. Kosmeder , Christopher Bieniarz
IPC分类号： G01N33/544 , G01N33/68 , C07F9/12 , C07F9/50 , C07F9/572 , C07F9/655 , G01N33/531 , G01N33/543 , G01N33/58
CPC分类号： G01N33/54346 , C07F9/12 , C07F9/5004 , C07F9/5022 , C07F9/5045 , C07F9/5728 , C07F9/65515 , C07F9/65517 , C07F9/65522 , G01N33/531 , G01N33/553 , G01N33/587 , G01N33/6854 , G01N2333/916
摘要： Disclosed herein are antibody-nanoparticle conjugates that include two or more nanoparticles (such as gold, palladium, platinum, silver, copper, nickel, cobalt, iridium, or an alloy of two or more thereof) directly linked to an antibody or fragment thereof through a metal-thiol bond. Methods of making the antibody-nanoparticle conjugates disclosed herein include reacting an arylphosphine-nanoparticle composite with a reduced antibody to produce an antibody-nanoparticle conjugate. Also disclosed herein are methods for detecting a target molecule in a sample that include using an antibody-nanoparticle conjugate (such as the antibody-nanoparticle conjugates described herein) and kits for detecting target molecules utilizing the methods disclosed herein.
摘要翻译： 本文公开了抗体 - 纳米颗粒缀合物，其包括直接连接到抗体或其片段的两个或更多个纳米颗粒（例如金，钯，铂，银，铜，镍，钴，铱或其两种或多种的合金） 金属硫醇键。 制备本文公开的抗体 - 纳米颗粒缀合物的方法包括使芳基膦 - 纳米颗粒复合物与还原抗体反应以产生抗体 - 纳米颗粒缀合物。 本文还公开了用于检测样品中靶分子的方法，其包括使用抗体 - 纳米颗粒缀合物（例如本文所述的抗体 - 纳米颗粒缀合物）和利用本文公开的方法检测靶分子的试剂盒。
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公开(公告)号：US08445191B2
公开(公告)日：2013-05-21
申请号：US13068144
申请日：2011-05-02
CPC分类号： G01N33/581 , A61K47/6883 , A61K49/0058 , A61K49/0067 , C07K17/08 , G01N33/532 , G01N33/54353 , G01N33/544 , G01N33/545 , G01N33/56983 , G01N33/57492 , G01N33/582 , G01N33/587 , G01N33/588
摘要： Certain disclosed embodiments of the present invention concern the synthesis, derivatization, conjugation to immunoglobulins and signal amplification based on discrete, relatively short polymers having plural reactive functional groups that react with plural molecules of interest. Reactive functional groups, such as hydrazides, may be derivatized with a variety of detectable labels, particularly haptens. The remaining reactive functional groups may be conjugated directly to a specific binding molecule, such as to the oxidized carbohydrate of the Fc region of the antibody. Disclosed conjugates display large signal amplification as compared to those based on molecules derivatized with single haptens, and are useful for assay methods, particularly multiplexed assays.
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7.发明授权Enzyme-catalyzed metal deposition for the enhanced in situ detection of immunohistochemical epitopes and nucleic acid sequences 有权酶催化的金属沉积用于增强免疫组织化学表位和核酸序列的原位检测公开(公告)号：US07632652B2
公开(公告)日：2009-12-15
申请号：US10877919
申请日：2004-06-24
IPC分类号： C12Q1/42 , C12Q1/44 , C12Q1/54 , C12Q1/68 , G01N33/53 , G01N33/543 , G01N33/567
CPC分类号： G01N33/581 , C07F9/093 , C07F9/65517 , C07F9/65522 , C07H15/20 , C07H15/24 , C07H15/26
摘要： The invention is directed to novel compositions of matter and methods of detecting in situ an immunohistochemical epitope or nucleic acid sequence of interest in a biological sample comprising binding an enzyme-labeled conjugate molecule to the epitope or sequence of interest in the presence of a redox-inactive reductive species and a soluble metal ion, thereby facilitating the reduction of the metal ion to a metal atom at or about the point where the enzyme is anchored. Novel phosphate derivatives of reducing agents are described that when exposed to a phosphatase are activated to their reducing form, thereby reducing metal ions to insoluble metal.
摘要翻译： 本发明涉及物质的新组合物和原位检测生物样品中感兴趣的免疫组织化学表位或核酸序列的方法，包括在氧化还原反应的存在下将酶标记的缀合物分子与感兴趣的表位或序列结合， 无活性还原物质和可溶性金属离子，从而有助于金属离子在酶被锚定的位置处或附近还原成金属原子。 描述了还原剂的新型磷酸酯衍生物，当暴露于磷酸酶被活化成其还原形式时，从而将金属离子还原成不溶性金属。
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8.发明申请公开(公告)号：US20100297725A1
公开(公告)日：2010-11-25
申请号：US12660744
申请日：2010-03-02
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
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.
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9.发明申请Haptens, hapten conjugates, compositions thereof and method for their preparation and use 有权半抗原，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。
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10.发明授权Haptens, hapten conjugates, compositions thereof and method for their preparation and use 有权半抗原，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。
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