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1. 发明公开

EP3561513A1 POLYMERIC CARRIERS FOR IMMUNOHISTOCHEMISTRY AND IN SITU HYBRIDIZATION 审中-公开
公开(公告)号：EP3561513A1
公开(公告)日：2019-10-30
申请号：EP19165476.3
申请日：2008-05-22
申请人： Ventana Medical Systems, Inc.
发明人： KOSMEDER, Jerry, W. , KERNAG, Casey, A. , JOHNSON, Donald , BIENIARZ, Christopher
IPC分类号： G01N33/533 , A61K49/00 , A61K47/68 , G01N33/68
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.

2. 发明授权

EP3224621B1 PROXIMITY ASSAYS USING CHEMICAL LIGATION AND HAPTEN TRANSFER 有权
公开(公告)号：EP3224621B1
公开(公告)日：2019-06-12
申请号：EP15798449.3
申请日：2015-11-24
申请人： Ventana Medical Systems, Inc.
发明人： BIENIARZ, Christopher , HONG, Rui
IPC分类号： G01N33/542

3. 发明公开

EP3095467A1 MOLECULAR CONJUGATE 无效
标题翻译：分子结合
公开(公告)号：EP3095467A1
公开(公告)日：2016-11-23
申请号：EP16001225.8
申请日：2006-11-21
申请人： Ventana Medical Systems, Inc.
发明人： BIENIARZ, Christopher , ASHWORTH-SHARPE, Julia , KERNAG, Casey A. , KOSMEDER, Jerome W. , LEFEVER, Mark
IPC分类号： A61K47/48
摘要： The present invention relates to conjugates comprising an antibody covalently bonded to a detectable label through a hydrazide thiol linker, wherein a hydrazide group of the linker is covalently bonded to an Fc region of the antibody, and wherein the detectable label is an enzyme having at least one thiol reactive group, wherein a thiol group of the hydrazide thiol linker is coupled to the at least one thiol reactive group of the enzyme. The present invention further relates to conjugates of an antibody and a modified phosphatase enzyme, the modified phosphatase enzyme comprising at least one thiol reactive group, wherein the antibody and the modified phosphatase enzyme are coupled through a mercaptobutyric acid hydrazide linker, and wherein a hydrazide group of the mercaptobutyric acid hydrazide linker is covalently bonded to an Fc region of the antibody.
摘要翻译：本发明涉及偶联物，其包含通过酰肼硫醇连接体与可检测标记共价结合的抗体，其中连接体的酰肼基团共价结合到抗体的Fc区，并且其中可检测标记是至少具有一个巯基反应性基团，其中酰肼巯基连接体的巯基偶联于该酶的至少一个巯基反应性基团。本发明进一步涉及抗体和修饰的磷酸酶的缀合物，所述修饰的磷酸酶包含至少一个硫醇反应性基团，其中抗体和修饰的磷酸酶通过巯基丁酸酰肼接头偶联，并且其中酰肼基团的巯基丁酸酰肼接头共价结合到抗体的Fc区。

4. 发明授权

EP2681334B1 APPLICATION OF QUANTUM DOTS FOR NUCLEAR STAINING 有权
标题翻译：量子点使用核着色剂
公开(公告)号：EP2681334B1
公开(公告)日：2016-06-15
申请号：EP12709822.6
申请日：2012-02-27
申请人： Ventana Medical Systems, Inc.
发明人： YUN, Chol, S. , KELLY, Brian, D. , ASHWORTH-SHARPE, Julia , BIENIARZ, Christopher , BAMFORD, Pascal , MURILLO, Adrian, E.
IPC分类号： C12Q1/68 , G01N33/533 , G01N33/58 , B82Y15/00
CPC分类号： G01N33/5308 , B82Y15/00 , C07D487/04 , C09B57/08 , C09B69/10 , C09B69/109 , C12Q1/6816 , C12Q1/6886 , C12Q2600/158 , G01N33/588 , C12Q2563/107 , C12Q2563/155

5. 发明公开

EP3029461A1 HAPTENS, HAPTEN CONJUGATES, COMPOSITIONS THEREOF AND METHOD FOR THEIR PREPARATION AND USE 有权
标题翻译：半抗原，半抗原结合物，其组合物和方法的生产和使用
公开(公告)号：EP3029461A1
公开(公告)日：2016-06-08
申请号：EP16151995.4
申请日：2007-11-01
申请人： Ventana Medical Systems, Inc.
发明人： KOSMEDER, Jerry , LEFEVER, Mark , JOHNSON, Donald , FARRELL, Michael , ZHILINA, Zhanna , BIENIARZ, Christopher
IPC分类号： G01N33/532 , C07K16/44 , C12Q1/68 , G01N33/533 , G01N33/58 , C07D495/04
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： Conjugate having a formula (hapten) - (linker)-(reactive group)-(carrier) are described, wherein the hapten is a quinoxaline, a thiazole sulfonamide or a benzofurazan; the linker, for coupling a hapten to a reactive group, is a polymer comprising from 1 to 15 ethylene glycol units. A method for detecting a molecule of interest in a biological sample is also described, comprising contacting the biological sample with a hapten-antibody conjugate or a nucleic acid hapten conjugate comprising an antibody or nucleic acid linked to the hapten using a heterobifunctional PEG linker, the hapten being a quinoxaline, a thiazole sulfonamide or a benzofurazan; and detecting a signal generated by the hapten conjugate after treatment with an anti-hapten antibody having at least one detectable label. Kits with a hapten, the hapten being a quinoxaline, a thiazole sulfonamide or a benzofurazan and an anti-hapten antibody are described.
摘要翻译：（接头） - - （反应性基团） - 具有下式的（半抗原）结合物（载体）中有所描述，worin半抗原是喹喔啉，噻唑磺酰胺或苯并呋咱; 左，用于半抗原偶联到反应性基团，是从1到15个乙二醇单元包含聚合物。因此描述了一种用于在生物样品中检测感兴趣的分子的方法，包括使用半抗原 - 抗体缀合物或核酸的半抗原缀合物的生物样品包括左抗体或核酸连接到使用异PEG的半抗原，所述半抗原是喹喔啉，噻唑磺酰胺或苯并呋咱; 和检测由与抗半抗原抗体，其具有至少一个可检测标记处理后的半抗原缀合物产生的信号。用半抗原的试剂盒，所述半抗原被描述喹喔啉，噻唑磺酰胺或苯并呋咱和抗半抗原抗体的。

6. 发明公开

EP2588443A2 HAPTEN CONJUGATES FOR TARGET DETECTION 审中-公开
标题翻译：半抗原结合物进行目标分子的检测
公开(公告)号：EP2588443A2
公开(公告)日：2013-05-08
申请号：EP11738526.0
申请日：2011-07-01
申请人： Ventana Medical Systems, Inc.
发明人： MURILLO, Adrian, E. , KOSMEDER, Jerome, W. , MAY, Eric , DAY, William , LEFEVER, Mark , PEDATA, Anne, M. , BIENIARZ, Christopher , MILLER, Phillip
IPC分类号： C07C213/00 , G01N33/58 , A61K47/48
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.

7. 发明公开

EP2167963A2 POLYMERIC CARRIERS FOR IMMUNOHISTOCHEMISTRY AND IN SITU HYBRIDIZATION 有权
标题翻译：的聚合物载体进行免疫组化和原位杂交
公开(公告)号：EP2167963A2
公开(公告)日：2010-03-31
申请号：EP08754680.0
申请日：2008-05-22
申请人： Ventana Medical Systems, Inc.
发明人： KOSMEDER, Jerry, W. , KERNAG, Casey, A. , JOHNSON, Donald , BIENIARZ, Christopher
IPC分类号： G01N33/533 , A61K49/00 , A61K47/48 , G01N33/68
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.

8. 发明公开

EP1877101A2 ENZYMES CONJUGATED TO ANTIBODIES VIA A PEG HETEROBIFUCTIONAL LINKER 有权
标题翻译：抗体在HETEROBIFUNTIONELLEN PEG-连接结合酶
公开(公告)号：EP1877101A2
公开(公告)日：2008-01-16
申请号：EP06758689.1
申请日：2006-04-27
申请人： Ventana Medical Systems, Inc.
发明人： BIENIARZ, Christopher , WONG, Jennifer , LEFEVER, Mark , KOSMEDER, Jerome W. , ASHWORTH-SHARPE, Julia , KERNAG, Casey, A.
IPC分类号： A61K47/48
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.

9. 发明授权

EP3095467B1 ANTIBODY-ENZYME CONJUGATE 无效
公开(公告)号：EP3095467B1
公开(公告)日：2020-05-06
申请号：EP16001225.8
申请日：2006-11-21
申请人： Ventana Medical Systems, Inc.
发明人： BIENIARZ, Christopher , ASHWORTH-SHARPE, Julia , KERNAG, Casey A. , KOSMEDER, Jerome W. , LEFEVER, Mark
IPC分类号： A61K47/62 , C12N9/16 , C07C319/02 , C07C323/60 , C07C327/28 , G01N33/535

10. 发明公开

EP3564674A1 HAPTENS, HAPTEN CONJUGATES, COMPOSITIONS THEREOF AND METHOD FOR THEIR PREPARATION AND USE 有权
公开(公告)号：EP3564674A1
公开(公告)日：2019-11-06
申请号：EP19178774.6
申请日：2007-11-01
申请人： Ventana Medical Systems, Inc.
发明人： KOSMEDER, Jerry , LEFEVER, Mark , JOHNSON, Donald , FARRELL, Michael , ZHILINA, Zhanna , BIENIARZ, Christopher
IPC分类号： G01N33/532 , G01N33/533 , G01N33/58 , C12Q1/68 , C07D271/12 , C07D495/04
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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