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1. 发明授权

US08877505B2 Composition and method for stabilizing fluorescent particles 有权
标题翻译：用于稳定荧光颗粒的组合物和方法
公开(公告)号：US08877505B2
公开(公告)日：2014-11-04
申请号：US13382509
申请日：2011-02-01
申请人： Eric May , Alexandra Nagy , Jerome Kosmeder
发明人： Eric May , Alexandra Nagy , Jerome Kosmeder
IPC分类号： G01N21/64 , C12Q1/68 , G01N33/533 , C09K11/02 , G01N33/58 , B82Y15/00
CPC分类号： C09K11/025 , B82Y15/00 , C09K11/883 , G01N33/533 , G01N33/588 , Y10S977/774 , Y10S977/902 , Y10T436/108331
摘要： Embodiments of a composition for stabilizing fluorescent signal of nanoparticles and methods for its use are disclosed. In some embodiments, the composition has a pH from 7 to 10 and includes borate, protein and/or protein hydrolysate, an amine, a preservative, and a nonionic surfactant. In particular embodiments, the amine is an N-ethanol substituted amine, such as ethanolamine, diethanolamine, triethanolamine, N-methyldiethanolamine, N,N-dimethylethanolamine, or a combination thereof. In some embodiments, a fluorescent particle solution, such as a quantum dot solution or quantum dot conjugate solution, is diluted in the composition and stored at 4° C. In certain embodiments, the fluorescence intensity of the diluted fluorescent particle remains substantially the same when stored at 4° C. for at least one month or at least three months. In particular embodiments, a diluted quantum dot conjugate is used to detect a hybridized probe or a protein antigen.
摘要翻译：公开了用于稳定纳米颗粒的荧光信号的组合物的实施方案及其使用方法。在一些实施方案中，组合物具有7至10的pH，并且包括硼酸盐，蛋白质和/或蛋白质水解产物，胺，防腐剂和非离子表面活性剂。在具体实施方案中，胺是N-乙醇取代的胺，例如乙醇胺，二乙醇胺，三乙醇胺，N-甲基二乙醇胺，N，N-二甲基乙醇胺或其组合。在一些实施方案中，将荧光颗粒溶液（例如量子点溶液或量子点共轭物溶液）在组合物中稀释并在4℃下储存。在某些实施方案中，稀释的荧光颗粒的荧光强度保持基本相同，当在4℃下储存至少一个月或至少三个月。在具体实施方案中，使用稀释的量子点缀合物来检测杂交的探针或蛋白质抗原。

2. 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。

3. 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.

4. 发明申请

US20110136130A1 METHOD FOR CHROMOGENIC DETECTION OF TWO OR MORE TARGET MOLECULES IN A SINGLE SAMPLE 有权
标题翻译：用于在单个样品中检测两种或更多种目标分子的方法
公开(公告)号：US20110136130A1
公开(公告)日：2011-06-09
申请号：US13059274
申请日：2009-08-21
申请人： Richard Gniewek , Michael Farrell , Hiroaki Nitta , Megan Lehrkamp , Jerome Kosmeder , Brian Daniel Kelly , Fabien Gaire , Mary Padilla , Thomas Grogan , Christopher Bieniarz
发明人： Richard Gniewek , Michael Farrell , Hiroaki Nitta , Megan Lehrkamp , Jerome Kosmeder , Brian Daniel Kelly , Fabien Gaire , Mary Padilla , Thomas Grogan , Christopher Bieniarz
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： C12Q1/6841 , G01N33/53 , G01N33/581 , G01N33/583
摘要： The present invention provides a method and kit for detection of two or more target molecules in a single tissue sample, such as for gene and protein dual detection in a single tissue sample. Methods comprise treating a tissue sample with a first binding moiety that specifically binds a first target molecule. Methods further comprise treating the tissue sample with a solution containing a soluble electron-rich aromatic compound prior to or concomitantly with contacting the tissue sample with a hapten-labeled binding moiety and detecting a second target molecule. In one example, the first target molecule is a protein and the second is a nucleic acid sequence, the first target molecule being detected by immunohistochemistry and the second by in situ hybridization. The disclosed method reduces background due to non-specific binding of the hapten-labeled specific binding moiety to an insoluble electron rich compound deposited near the first target molecule.
摘要翻译：本发明提供了用于检测单个组织样品中两种或更多种靶分子的方法和试剂盒，例如用于单一组织样品中的基因和蛋白质双重检测。方法包括用特异性结合第一靶分子的第一结合部分处理组织样品。方法还包括在使组织样品与半抗原标记的结合部分接触或同时检测第二靶分子之前或同时使用含有可溶于富电子的芳族化合物的溶液处理组织样品。在一个实例中，第一靶分子是蛋白质，第二个是核酸序列，第一个靶分子通过免疫组织化学检测，第二个是原位杂交。所公开的方法由于半抗原标记的特异性结合部分与沉积在第一靶分子附近的不溶性富电子化合物的非特异性结合而减少背景。

5. 发明申请

US20050158770A1 Microwave mediated synthesis of nucleic acid probes 有权
标题翻译：微波介导的核酸探针合成
公开(公告)号：US20050158770A1
公开(公告)日：2005-07-21
申请号：US11018897
申请日：2004-12-21
申请人： Christopher Bieniarz , Michael Farrell , Jerome Kosmeder , Mark Lefever
发明人： Christopher Bieniarz , Michael Farrell , Jerome Kosmeder , Mark Lefever
IPC分类号： C07H21/04 , C12N13/00 , C12Q1/68 , C40B40/06 , H05B6/64
CPC分类号： C07H21/00 , B01J2219/00452 , B01J2219/00572 , B01J2219/00576 , B01J2219/00722 , C40B40/06
摘要： A method for preparing a nucleic acid probe is provided. The method comprises forming an activated cytosine or cytidine by a bisulfite catalyzed reaction; and covalently linking a reporter molecule to the activated cytosine or cytidine, wherein said activating step, said covalently linking step, or both are conducted in the presence of microwave energy. Also provided by the invention are nucleic acid probes.
摘要翻译：提供了制备核酸探针的方法。该方法包括通过亚硫酸氢盐催化反应形成活化的胞嘧啶或胞苷; 并将报告分子与活化的胞嘧啶或胞苷共价连接，其中所述活化步骤，所述共价连接步骤或两者均在微波能量存在下进行。本发明还提供了核酸探针。

6. 发明申请

US20220026319A1 COMPOSITIONS AND METHODS FOR SIMULTANEOUS INACTIVATION OF ALKALINE PHOSPHATASE AND PEROXIDASE ENZYMES DURING AUTOMATED MULTIPLEX TISSUE STAINING ASSAYS 有权
公开(公告)号：US20220026319A1
公开(公告)日：2022-01-27
申请号：US17493477
申请日：2021-10-04
申请人： James Grille , Brian D. Kelly , Jerome Kosmeder, II , Eric May , Noemi Sebastiao , Pamela Wirth
发明人： James Grille , Brian D. Kelly , Jerome Kosmeder, II , Eric May , Noemi Sebastiao , Pamela Wirth
IPC分类号： G01N1/30 , G01N33/52 , C07C55/02 , C01B21/08 , C07C55/22 , C07C55/24 , C01B15/01
摘要： Disclosed are compositions and methods for inactivating one or more enzymes in a biological sample.

7. 发明授权

US08481270B2 Method for chromogenic detection of two or more target molecules in a single sample 有权
标题翻译：一种样品中两种或更多种靶分子的显色检测方法
公开(公告)号：US08481270B2
公开(公告)日：2013-07-09
申请号：US13059274
申请日：2009-08-21
申请人： Richard Gniewek , Michael Farrell , Hiroaki Nitta , Megan Lehrkamp , Jerome Kosmeder , Brian Daniel Kelly , Thomas Grogan , Fabien Gaire , Mary Padilla , Christopher Bieniarz
发明人： Richard Gniewek , Michael Farrell , Hiroaki Nitta , Megan Lehrkamp , Jerome Kosmeder , Brian Daniel Kelly , Thomas Grogan , Fabien Gaire , Mary Padilla , Christopher Bieniarz
IPC分类号： C12Q1/68 , G01N33/58 , G01N33/53
CPC分类号： C12Q1/6841 , G01N33/53 , G01N33/581 , G01N33/583
摘要： The present invention provides a method and kit for detection of two or more target molecules in a single tissue sample, such as for gene and protein dual detection in a single tissue sample. Methods comprise treating a tissue sample with a first binding moiety that specifically binds a first target molecule. Methods further comprise treating the tissue sample with a solution containing a soluble electron-rich aromatic compound prior to or concomitantly with contacting the tissue sample with a hapten-labeled binding moiety and detecting a second target molecule. In one example, the first target molecule is a protein and the second is a nucleic acid sequence, the first target molecule being detected by immunohistochemistry and the second by in situ hybridization. The disclosed method reduces background due to non-specific binding of the hapten-labeled specific binding moiety to an insoluble electron rich compound deposited near the first target molecule.
摘要翻译：本发明提供了用于检测单个组织样品中两种或更多种靶分子的方法和试剂盒，例如用于单一组织样品中的基因和蛋白质双重检测。方法包括用特异性结合第一靶分子的第一结合部分处理组织样品。方法还包括在使组织样品与半抗原标记的结合部分接触或同时检测第二靶分子之前或同时使用含有可溶于富电子的芳族化合物的溶液处理组织样品。在一个实例中，第一靶分子是蛋白质，第二个是核酸序列，第一个靶分子通过免疫组织化学检测，第二个是原位杂交。所公开的方法由于半抗原标记的特异性结合部分与沉积在第一靶分子附近的不溶性富电子化合物的非特异性结合而减少背景。

8. 发明申请

US20120122094A1 COMPOSITION AND METHOD FOR STABILIZING FLUORESCENT PARTICLES 有权
标题翻译：用于稳定荧光颗粒的组合物和方法
公开(公告)号：US20120122094A1
公开(公告)日：2012-05-17
申请号：US13382509
申请日：2011-02-01
申请人： Eric May , Alexandra Nagy , Jerome Kosmeder
发明人： Eric May , Alexandra Nagy , Jerome Kosmeder
IPC分类号： G01N21/64 , C12Q1/68 , B82Y15/00
CPC分类号： C09K11/025 , B82Y15/00 , C09K11/883 , G01N33/533 , G01N33/588 , Y10S977/774 , Y10S977/902 , Y10T436/108331
摘要： Embodiments of a composition for stabilizing fluorescent signal of nanoparticles and methods for its use are disclosed. In some embodiments, the composition has a pH from 7 to 10 and includes borate, protein and/or protein hydrolysate, an amine, a preservative, and a nonionic surfactant. In particular embodiments, the amine is an N-ethanol substituted amine, such as ethanolamine, diethanolamine, triethanolamine, N-methyldiethanolamine, N,N-dimethylethanolamine, or a combination thereof. In some embodiments, a fluorescent particle solution, such as a quantum dot solution or quantum dot conjugate solution, is diluted in the composition and stored at 4° C. In certain embodiments, the fluorescence intensity of the diluted fluorescent particle remains substantially the same when stored at 4° C. for at least one month or at least three months. In particular embodiments, a diluted quantum dot conjugate is used to detect a hybridized probe or a protein antigen.
摘要翻译：公开了用于稳定纳米颗粒的荧光信号的组合物的实施方案及其使用方法。在一些实施方案中，组合物具有7至10的pH，并且包括硼酸盐，蛋白质和/或蛋白质水解产物，胺，防腐剂和非离子表面活性剂。在具体实施方案中，胺是N-乙醇取代的胺，例如乙醇胺，二乙醇胺，三乙醇胺，N-甲基二乙醇胺，N，N-二甲基乙醇胺或其组合。在一些实施方案中，将荧光颗粒溶液（例如量子点溶液或量子点共轭物溶液）在组合物中稀释并在4℃下储存。在某些实施方案中，稀释的荧光颗粒的荧光强度保持基本相同，当在4℃下储存至少一个月或至少三个月。在具体实施方案中，使用稀释的量子点缀合物来检测杂交的探针或蛋白质抗原。

9. 发明申请

US20070172911A1 Biological sample processing composition and method 审中-公开
标题翻译：生物样品处理组成及方法
公开(公告)号：US20070172911A1
公开(公告)日：2007-07-26
申请号：US11652915
申请日：2007-01-12
申请人： Michael Farrell , Christopher Bieniarz , Kurt Reinhardt , Glen Ward , Jerome Kosmeder , Andrew Ghusson , Eric Walk , Guadalupe Manriquez , Thomas Grogan
发明人： Michael Farrell , Christopher Bieniarz , Kurt Reinhardt , Glen Ward , Jerome Kosmeder , Andrew Ghusson , Eric Walk , Guadalupe Manriquez , Thomas Grogan
IPC分类号： G01N1/30 , G01N33/48
CPC分类号： G01N1/30
摘要： A method and composition are disclosed that are useful for processing biological samples. In one aspect, a biological sample such as a tissue section is treated using a histochemical technique and is contacted with a lipid compound during the process to enhance the definition of cellular and sub-cellular features that are observable in the sample when it is viewed microscopically. In other aspects, a coverslipping composition that includes a lipid compound and a method of coverslipping a sample using the coverslipping composition are disclosed.
摘要翻译：公开了可用于处理生物样品的方法和组合物。在一个方面，使用组织化学技术处理诸如组织切片的生物样品，并且在该过程期间与脂质化合物接触以增强在微观观察时在样品中可观察到的细胞和亚细胞特征的定义。在其它方面，公开了一种包括脂质化合物的覆盖组合物和使用盖玻片组合物覆盖样品的方法。

10. 发明申请

US20070072835A1 Method of preparing and use of prodrugs of betulinic acid derivatives 审中-公开
标题翻译：制备和使用桦木酸衍生物前药的方法
公开(公告)号：US20070072835A1
公开(公告)日：2007-03-29
申请号：US11477177
申请日：2006-06-28
申请人： John Pezzuto , Jerome Kosmeder , Ze-Qi Xu , Nian Zhou , Miriam Goldsmith
发明人： John Pezzuto , Jerome Kosmeder , Ze-Qi Xu , Nian Zhou , Miriam Goldsmith
IPC分类号： A61K31/56
CPC分类号： C07J1/00 , A61K31/56 , C07J63/008
摘要： A composition and method of preventing or inhibiting tumor growth and, more particularly, of treating a malignant tumor, using prodrugs of plant-derived compounds and derivatives is disclosed. In the method, a composition containing betulinic acid or a betulinic acid derivative is administered in a prodrug form to release betulinic acid or a betulinic acid derivative in vivo at the tumor site.
摘要翻译：公开了使用植物衍生化合物和衍生物的前药来预防或抑制肿瘤生长，更具体地治疗恶性肿瘤的组合物和方法。在该方法中，含有桦木酸或桦木酸衍生物的组合物以前药形式给药以在肿瘤部位体内释放桦木酸或桦木酸衍生物。

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