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71. 发明授权

US07358052B2 Catalytic amplification of multiplexed assay signals 有权
标题翻译：多重测定信号的催化扩增
公开(公告)号：US07358052B2
公开(公告)日：2008-04-15
申请号：US10154641
申请日：2002-05-24
申请人： Sharat Singh
发明人： Sharat Singh
IPC分类号： G01N33/53 , G01N33/533 , C12Q1/42
CPC分类号： G01N33/561 , C12Q1/6823 , G01N2458/10 , C12Q2537/143 , C12Q2565/125
摘要： Methods, compositions, kits, and a system are disclosed for detecting one or more analytes in a sample. A mixture comprising the (i) sample, (ii) a first binding reagent comprising a cleavage-inducing moiety and a first binding agent specific for an analyte, and (ii) one or more electrophoretic probes each having a second binding agent is subjected to conditions under which binding of respective binding agents occurs. The interaction between the binding agents and the analyte brings the cleavage-inducing moiety within a proximity effective for cleaving a cleavable linkage tethering an electrophoretic tag to the second binding agent, thereby releasing the tag for electrophoretic separation. Separation of different tags occurs by virtue of their distinct electrophoretic mobilities. After separation, a signal amplification moiety on each tag is activated to generate a signal to indicate the presence of a particular analyte in the sample.
摘要翻译：公开了用于检测样品中一种或多种分析物的方法，组合物，试剂盒和系统。将包含（i）样品，（ii）包含切割诱导部分的第一结合试剂和对分析物特异性的第一结合剂的混合物和（ii）每个具有第二结合剂的一个或多个电泳探针经受发生各自结合剂结合的条件。结合剂和分析物之间的相互作用使得切割诱导部分在接近范围内有效，用于切割将电泳标签连接到第二结合剂的可切割连接，从而释放用于电泳分离的标签。不同标签的分离由于其不同的电泳迁移率而发生。分离后，激活每个标签上的信号放大部分以产生信号以指示样品中特定分析物的存在。

72. 发明申请

US20070254295A1 METHODS OF PREDICTING AND MONITORING TYROSINE KINASE INHIBITOR THERAPY 有权
标题翻译：预测和监测酪氨酸激酶抑制剂治疗方法
公开(公告)号：US20070254295A1
公开(公告)日：2007-11-01
申请号：US11687254
申请日：2007-03-16
申请人： Jeanne Harvey , Bruce Neri , Sharat Singh
发明人： Jeanne Harvey , Bruce Neri , Sharat Singh
IPC分类号： G01N33/53 , A61P35/00 , C12Q1/68
CPC分类号： G06F19/18 , C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , G01N33/57484 , G01N2333/91215 , G01N2500/04 , G01N2800/52 , G06F19/24
摘要： The present invention provides methods for analyzing a combination of biomarkers to individualize tyrosine kinase inhibitor therapy in patients who have been diagnosed with cancer. In particular, the assay methods of the present invention are useful for predicting, identifying, or monitoring the response of a tumor, tumor cell, or patient to treatment with a tyrosine kinase inhibitor using an algorithm based upon biomarker profiling. The assay methods of the present invention are also useful for predicting whether a patient has a risk of developing toxicity or resistance to treatment with a tyrosine kinase inhibitor. In addition, the assay methods of the present invention are useful for monitoring tyrosine kinase inhibitor therapy in a patient receiving the drug to evaluate whether the patient will develop resistance to the drug. Furthermore, the assay methods of the present invention are useful for optimizing the dose of a tyrosine kinase inhibitor in a patient receiving the drug to achieve therapeutic efficacy and/or reduce toxic side-effects.
摘要翻译：本发明提供了用于分析已经被诊断患有癌症的患者中的酪氨酸激酶抑制剂治疗的生物标志物的组合的方法。特别地，本发明的测定方法可用于使用基于生物标志物分析的算法预测，鉴定或监测肿瘤，肿瘤细胞或患者用酪氨酸激酶抑制剂治疗的应答。本发明的测定方法也可用于预测患者是否具有产生毒性或抗酪氨酸激酶抑制剂治疗的风险。此外，本发明的测定方法可用于监测接受药物的患者中的酪氨酸激酶抑制剂治疗，以评估患者是否会产生对药物的抗药性。此外，本发明的测定方法可用于优化接受该药物的患者中的酪氨酸激酶抑制剂的剂量以达到治疗功效和/或减少毒副作用。

73. 发明授权

US07255999B2 Methods and compositions for analyzing proteins 有权
标题翻译：用于分析蛋白质的方法和组合物
公开(公告)号：US07255999B2
公开(公告)日：2007-08-14
申请号：US10154042
申请日：2002-05-21
申请人： Sharat Singh , Hossein Salimi-Moosavi , Syed Hasan Tahir , Gerald J. Wallweber , Hrair Kirakossian , Tracy J. Matray , Vincent S. Hernandez
发明人： Sharat Singh , Hossein Salimi-Moosavi , Syed Hasan Tahir , Gerald J. Wallweber , Hrair Kirakossian , Tracy J. Matray , Vincent S. Hernandez
IPC分类号： G01N33/53 , G01N33/533 , C12Q1/42
CPC分类号： G01N33/6842 , C07K16/00 , C07K2317/40 , G01N33/582 , G01N33/6803
摘要： Methods, compositions and kits are disclosed for determining one or more target polypeptides in a sample where the target polypeptides have undergone a post-translational modification. A mixture comprising the sample and a first reagent comprising a cleavage-inducing moiety and a first binding agent for a binding site on a target polypeptide is subjected to conditions under which binding of respective binding moieties occurs. The binding site is the result of post-translational modification activity involving the target polypeptide. The method may be employed to determine the target polypeptide itself. In another embodiment the presence and/or amount of the target polypeptide is related to the presence and/or amount and/or activity of an agent such as an enzyme involved in the post-translational modification of the target polypeptide. The interaction between the first binding agent and the binding site brings the cleavage-inducing moiety into close proximity to a cleavable moiety, which is associated with the polypeptide and is susceptible to cleavage only when in proximity to the cleavage-inducing moiety. In this way, an electrophoretic tag for each of the polypeptides may be released. Released electrophoretic tags are separated and the presence and/or amount of the target polypeptides are determined based on the corresponding electrophoretic tags.
摘要翻译：公开了用于确定样品中一种或多种靶多肽已经经历了翻译后修饰的方法，组合物和试剂盒。包含样品和包含切割诱导部分的第一试剂和用于靶多肽上的结合位点的第一结合剂的混合物经受各自结合部分的结合发生的条件。结合位点是涉及靶多肽的翻译后修饰活性的结果。该方法可用于确定靶多肽本身。在另一个实施方案中，靶多肽的存在和/或量与试剂例如涉及靶多肽的翻译后修饰的酶的存在和/或量和/或活性有关。第一结合剂和结合位点之间的相互作用使切割诱导部分紧密接近可切割部分，其可与多肽相关，并且仅在接近切割诱导部分时易于切割。以这种方式，可以释放每个多肽的电泳标签。分离释放的电泳标签，并且基于相应的电泳标签确定靶多肽的存在和/或量。

74. 发明申请

US20060223107A1 Detection of nucleic acid sequences by cleavage and separation of tag-containing structures 审中-公开
标题翻译：通过裂解和分离含标记结构来检测核酸序列
公开(公告)号：US20060223107A1
公开(公告)日：2006-10-05
申请号：US11447753
申请日：2006-06-05
申请人： Ahmed Chenna , Vivian Xiao , Sharat Singh
发明人： Ahmed Chenna , Vivian Xiao , Sharat Singh
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6816 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C12Q1/682 , C12Q1/6823 , C40B20/08 , C40B40/08 , C40B50/16 , C40B70/00 , C12Q2565/125 , C12Q2537/162 , C12Q2521/301 , C12Q2537/125 , C12Q2525/161
摘要： The present invention is directed to a method of detecting pluralities of target nucleic acid sequences by forming and cleaving duplex structures with a pair of probes, one probe of each pair being labeled with an electrophoretic tag. Cleavage of the duplex structures releases electrophoretic tags that are then separated and identified to indicate the presence or quantity of the target sequences. The present invention is particularly useful in multiplex reactions wherein multiple target sequences are detected in one reaction. Kits useful in the detection of nucleic acids are also provided.
摘要翻译：本发明涉及通过用一对探针形成和切割双链体结构来检测多个靶核酸序列的方法，每对中的一个探针用电泳标签标记。双链结构的切割释放电泳标签，然后将其分离并鉴定以指示靶序列的存在或数量。本发明特别适用于在一个反应中检测多个靶序列的多重反应。还提供了用于检测核酸的试剂盒。

75. 发明授权

US06955874B2 Kits employing oligonucleotide-binding e-tag probes 失效
标题翻译：使用寡核苷酸结合电子标签探针的试剂盒
公开(公告)号：US06955874B2
公开(公告)日：2005-10-18
申请号：US09824905
申请日：2001-04-02
申请人： Sharat Singh , Tracy Matray , Ahmed Chenna
发明人： Sharat Singh , Tracy Matray , Ahmed Chenna
IPC分类号： C12N15/09 , C07B61/00 , C07H19/06 , C07H19/10 , C07H21/00 , C12Q1/68 , B65D69/00 , C07H21/02 , C07H21/04 , G01H27/26
CPC分类号： C07H19/06 , C07H19/10 , C07H21/00 , C40B70/00 , G01N33/561 , Y10S435/81
摘要： Kits for the multiplexed detection of known, selected nucleotide target sequences are provided. Detection involves the release of identifying tags as a consequence of target recognition. The kits include sets of electrophoretic tag probes or e-tag probes, capture agent and optionally a nuclease. The e-tag probes comprise a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. In using the kits, the target-binding moiety of the e-tag probes hybridizes to complementary target sequences followed by nuclease cleavage of the e-tag probes and release of detectable e-tags or e-tag reporters. The mixture is exposed to a capture agent which binds uncleaved and/or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.
摘要翻译：提供了用于已知选择的核苷酸靶序列的多重检测的试剂盒。检测涉及到识别标签作为目标识别的结果。该试剂盒包括一组电泳标签探针或电子标签探针，捕获剂和任选的核酸酶。电子标签探针包括检测区域和称为迁移率调节剂的迁移率限定区域，两者都与靶结合部分连接。在使用试剂盒时，e-标签探针的靶结合部分与互补的靶序列杂交，随后是e-标签探针的核酸酶切割和可检测的电子标签或电子标签记录的释放。将混合物暴露于捕获剂，其结合未切割和/或部分切割的e-标签探针，然后进行电泳分离。在多重测定中，可以分离和检测不同的释放的电子标签记录器，以提供目标识别。

76. 发明授权

US06916667B2 Metal chelate containing compositions for use in chemiluminescent assays 有权
标题翻译：含金属螯合物的组合物用于化学发光测定
公开(公告)号：US06916667B2
公开(公告)日：2005-07-12
申请号：US10730139
申请日：2003-12-09
申请人： Sharat Singh , Edwin F. Ullman
发明人： Sharat Singh , Edwin F. Ullman
IPC分类号： G01N33/532 , C07D265/30 , C07D279/12 , C07D327/06 , C07D413/04 , C07F5/00 , C07F15/00 , C12Q1/26 , G01N21/78 , G01N33/53 , G01N33/533 , G01N33/542 , G01N33/543 , G01N33/58 , G01N33/546 , G01N33/78
CPC分类号： C07D265/30 , C07D279/12 , C07D327/06 , C07D413/04 , G01N33/533 , G01N33/54313 , G01N33/5436 , G01N33/58 , G01N33/582 , G01N33/585 , G01N33/586 , Y10S435/968 , Y10S436/80 , Y10S436/805 , Y10S436/808 , Y10T436/13
摘要： Compositions are disclosed comprising (a) a metal chelate wherein the metal is selected from the group consisting of europium, terbium, dysprosium, samarium osmium and ruthenium in at least a hexacoordinated state and (b) a compound having a double bond substituted with two aryl groups, an oxygen atom and an atom selected from the group consisting of oxygen, sulfur and nitrogen wherein one of the aryl groups is electron donating with respect to the other. Such composition is preferably incorporated in a latex particulate material. Methods and kits are also disclosed for determining an analyte in a medium suspected of containing the analyte. The methods and kits employ as one component a composition as described above.
摘要翻译：公开了包含（a）金属螯合物的组合物，其中金属选自铕，铽，镝，钐锇和钌至少六配位状态，和（b）具有被两个芳基取代的双键的化合物基团，氧原子和选自氧，硫和氮的原子，其中一个芳基相对于另一个赋予电子。这种组合物优选掺入胶乳颗粒材料中。还公开了用于测定怀疑含有分析物的培养基中的分析物的方法和试剂盒。所述方法和试剂盒采用如上所述的组合物作为一种组分。

77. 发明授权

US06703248B1 Particles for diagnostic and therapeutic use 有权
公开(公告)号：US06703248B1
公开(公告)日：2004-03-09
申请号：US09465065
申请日：1999-12-15
申请人： Sharat Singh , John S. Pease , Jacqueline Sadakian , Daniel B. Wagner , Edwin F. Ullman
发明人： Sharat Singh , John S. Pease , Jacqueline Sadakian , Daniel B. Wagner , Edwin F. Ullman
IPC分类号： G01N33553
CPC分类号： G01N33/587 , C12Q1/6816 , Y10T436/10 , C12Q2563/155 , C12Q2523/319
摘要： Methods, compositions and kits are disclosed. The compositions are light emitting and comprise a polymeric matrix having dissolved therein a photoactive compound. The composition has the characteristic that, after activation of the photoactive compound, the rate of decrease in the intensity of light emission at any time during a 20-fold decrease in the intensity is proportional to the intensity of the light emission. In one embodiment the polymeric matrix is comprised of particles of about 20 nm to about 100 &mgr;m in diameter to which is bound a specific binding pair member. The particles generally comprise a polymeric matrix having dissolved therein about 1 to about 20% by weight of a dopant. The compositions may be used in methods for determining an analyte. A combination is provided comprising (1) a medium suspected of containing the analyte, (2) and the aforementioned composition. The photoactive substance is activated and the effect of the activating on the optical properties of the combination is detected. The presence and amount of the effect is related to the presence and amount of the analyte in the medium. Also disclosed are kits for use in an assay.

78. 发明授权

US06686152B2 Methods employing oligonucleotide-binding e-tag probes 失效
标题翻译：使用寡核苷酸结合电子标签探针的方法
公开(公告)号：US06686152B2
公开(公告)日：2004-02-03
申请号：US09825247
申请日：2001-04-02
申请人： Sharat Singh , Huan Tian
发明人： Sharat Singh , Huan Tian
IPC分类号： C12P168
CPC分类号： C07H19/06 , C07H19/10 , C07H21/00 , C40B70/00 , G01N33/561 , Y10S435/81
摘要： Methods for the multiplexed detection of known, selected nucleotide target sequences are provided. Detection involves the release of identifying tags as a consequence of target recognition. The methods include the use of electrophoretic tag probes or e-tag probes, comprising a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. In practicing the methods, the target-binding moiety of the e-tag probes hybridizes to complementary target sequences followed by nuclease cleavage of the e-tag probes and release of detectable e-tags or e-tag reporters. The mixture is exposed to a capture agent which binds uncleaved and/or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.
摘要翻译：提供了多种检测已知选择的核苷酸靶序列的方法。检测涉及到识别标签作为目标识别的结果。所述方法包括使用电泳标签探针或电子标签探针，其包含与靶结合部分连接的检测区域和称为迁移率调节剂的迁移率限定区域。在实施该方法时，e-标签探针的靶结合部分与互补靶序列杂交，随后是e-标签探针的核酸酶切割和可检测的电子标签或电子标签记录的释放。将混合物暴露于捕获剂，其结合未切割和/或部分切割的e-标签探针，然后进行电泳分离。在多重测定中，可以分离和检测不同的释放的电子标签记录器，以提供目标识别。

79. 发明授权

US06649351B2 Methods for detecting a plurality of analytes by mass spectrometry 有权
公开(公告)号：US06649351B2
公开(公告)日：2003-11-18
申请号：US10008593
申请日：2001-11-09
申请人： Tracy J. Matray , Vincent S. Hernandez , Ahmed Chenna , Herbert Hooper , Sharat Singh
发明人： Tracy J. Matray , Vincent S. Hernandez , Ahmed Chenna , Herbert Hooper , Sharat Singh
IPC分类号： C12Q168
CPC分类号： C07H19/06 , C07H19/10 , C07H21/00 , C12Q1/6816 , C40B20/08 , C40B40/08 , C40B50/16 , C40B70/00 , G01N33/561 , C12Q2521/319 , C12Q2563/131 , C12Q2565/627
摘要： The invention provides a method for detecting a target analyte, by: (a) contacting one or more target analytes with a set of first and second binding reagents under conditions sufficient for binding of a target analyte with the first and second binding reagents, each of the first binding reagents containing a cleavage-inducing moiety and a target binding moiety, each of the second binding reagents containing a tagged probe having a mass modifier region attached to a target binding moiety by a cleavable linkage, the cleavable linkage being susceptible to cleavage when in proximity to an activated cleavage-inducing moiety; (b) activating the cleavage-inducing moiety to release a tag reporter, and (c) detecting a mass of the tag reporter, the mass uniquely corresponding to a known target analyte.

80. 发明授权

US06613525B2 Microfluidic apparatus and method for purification and processing 有权
标题翻译：微流控装置及其净化处理方法
公开(公告)号：US06613525B2
公开(公告)日：2003-09-02
申请号：US10051847
申请日：2002-01-17
申请人： Robert J. Nelson , Herbert H. Hooper , Alan K. Hauser , Sharat Singh , Stephen J. Williams , Alexander P. Sassi
发明人： Robert J. Nelson , Herbert H. Hooper , Alan K. Hauser , Sharat Singh , Stephen J. Williams , Alexander P. Sassi
IPC分类号： C12Q168
CPC分类号： G01N27/44743 , B01F13/0059 , B01L3/50273 , B01L3/502753 , B01L3/502761 , B01L7/52 , B01L2200/0631 , B01L2200/0668 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/087 , B01L2300/0877 , B01L2400/0409 , B01L2400/0415 , B01L2400/0421 , G01N27/44791 , G01N33/5002 , G01N33/569
摘要： Integrated microfluidic devices comprising at least an enrichment channel (10) and a main electrophoretic flowpath (12) are provided. In the subject integrated devices, the enrichment channel and the main electrophoretic flowpath are positioned so that waste fluid flows away from said main electrophoretic flowpath through a discharge outlet (6). The subject devices find use in a variety of electrophoretic applications, including clinical assays, high throughput screening for genomics and pharmaceutical applications, point-or-care in vitro diagnostics, molecular genetic analysis and nucleic acid diagnostics, cell separations, and bioresearch generally.
摘要翻译：提供包括至少富集通道（10）和主电泳流路（12）的集成微流体装置。在主题集成装置中，富集通道和主电泳流路被定位成使得废液通过排出口（6）离开所述主电泳流路。主题装置可用于各种电泳应用，包括临床测定，基因组学和药物应用的高通量筛选，点对点护理体外诊断，分子遗传分析和核酸诊断，细胞分离和生物研究。

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