公开(公告)号：US20090035792A1

公开(公告)日：2009-02-05

申请号：US12172100

申请日：2008-07-11

申请人： Sharat Singh ,  Jeanne Harvey

发明人： Sharat Singh ,  Jeanne Harvey

IPC分类号： G01N33/574 ,  C12M1/34

CPC分类号： G01N33/57423 ,  G01N33/5041 ,  G01N33/5044 ,  G01N33/5082 ,  G01N2500/10 ,  G01N2800/52

摘要： The present invention provides compositions and methods for detecting the activation states of components of signal transduction pathways in tumor cells. Information on the activation states of components of signal transduction pathways derived from use of the invention can be used for cancer diagnosis, prognosis, and in the design of cancer treatments.

摘要翻译： 本发明提供用于检测肿瘤细胞中信号转导途径的组分的激活状态的组合物和方法。 关于使用本发明的信号转导途径的组分的激活状态的信息可用于癌症诊断，预后和癌症治疗的设计。

公开(公告)号：US20080311674A1

公开(公告)日：2008-12-18

申请号：US11837427

申请日：2007-08-10

申请人： Sharat Singh ,  Hossein Salimi-Moosavi ,  Syed Hasan Tahir ,  Gerald J. Wallweber ,  Hrair Kirakossian ,  Tracey J. Matray ,  Vincent S. Hernandez

发明人： Sharat Singh ,  Hossein Salimi-Moosavi ,  Syed Hasan Tahir ,  Gerald J. Wallweber ,  Hrair Kirakossian ,  Tracey J. Matray ,  Vincent S. Hernandez

IPC分类号： G01N27/26 ,  G01N33/53

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。

公开(公告)号：US07402399B2

公开(公告)日：2008-07-22

申请号：US10963855

申请日：2004-10-13

申请人： Ali Mukherjeei ,  Mengxiang Tang ,  Harprit S. Pannu ,  Po-Ying Chan-Hui ,  Sharat Singh

发明人： Ali Mukherjeei ,  Mengxiang Tang ,  Harprit S. Pannu ,  Po-Ying Chan-Hui ,  Sharat Singh

IPC分类号： G01N33/53 ,  G01N33/533

CPC分类号： G01N33/74 ,  G01N33/5041 ,  G01N33/57492 ,  G01N33/6893 ,  G01N2333/485

摘要： The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

摘要翻译： 本发明提供了通过测量受体二聚化和RTK途径特征的蛋白质 - 蛋白复合物或活化的效应蛋白的相对量来确定细胞样品或患者样品中受体酪氨酸激酶（RTK）途径的激活状态的方法。 本发明还提供了使用这种状态信息来选择对途径特异性药物有反应的患者的方法，更具体地，涉及用于测量ErbB受体和受体复合物的方法，并使用这些信息来选择对ErbB途径特异性药物有反应的患者。 优选地，本发明的方法通过使用具有可释放分子标签的结合化合物组来实现，所述可释放分子标签对于在RTK活化中形成的一种或多种复合物的多种组分是特异性的。 结合后，分离标签被释放并与测定混合物分离，用于分析。

公开(公告)号：US07402397B2

公开(公告)日：2008-07-22

申请号：US10916291

申请日：2004-08-10

申请人： Po-Ying Chan-Hui ,  Sharat Singh ,  Hossein Salimi-Moosavi ,  Hasan Tahir ,  Gerald J. Wallweber ,  Hrair Kirakosssian ,  Tracy J. Matray

发明人： Po-Ying Chan-Hui ,  Sharat Singh ,  Hossein Salimi-Moosavi ,  Hasan Tahir ,  Gerald J. Wallweber ,  Hrair Kirakosssian ,  Tracy J. Matray

IPC分类号： G01N33/53 ,  G01N33/532 ,  G01N33/554 ,  C07K1/10 ,  C07K1/14

CPC分类号： G01N33/542 ,  G01N33/566 ,  G01N2333/71 ,  G01N2333/726 ,  Y10S436/824

摘要： Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.

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。

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。

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。

公开(公告)号：US07122319B2

公开(公告)日：2006-10-17

申请号：US10702269

申请日：2003-11-05

申请人： Linda Liu ,  Po-Ying Chan-Hui ,  Hrair Kirakossian ,  Sharat Singh

发明人： Linda Liu ,  Po-Ying Chan-Hui ,  Hrair Kirakossian ,  Sharat Singh

IPC分类号： C12Q1/68 ,  G01N33/53

CPC分类号： G01N27/44726 ,  C12Q1/6823 ,  C12Q2521/301 ,  C12Q2527/113 ,  C12Q2537/162

摘要： Methods and compositions are provided for detection of analytes, such as cell surface moieties, preferably in multiplexed assays, such that multiple analytes can be assayed simultaneously. The methods employ analyte binding agents which are linked to oligonucleotide labels, which labels are then used for formation of cleavage structures and generation of detectable molecular tags. Preferably, multiple tags are generated per analyte binding event.

摘要翻译： 提供了用于检测分析物的方法和组合物，例如细胞表面部分，优选在多重测定中，使得可以同时测定多种分析物。 该方法使用与寡核苷酸标签连接的分析物结合剂，然后将该标记物用于形成切割结构和产生可检测的分子标签。 优选地，每个分析物结合事件产生多个标签。

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。

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。