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1. 发明申请

WO2012162373A8 ROS KINASE IN LUNG CANCER 审中-公开
标题翻译： ROS在肺癌中发生
公开(公告)号：WO2012162373A8
公开(公告)日：2016-05-19
申请号：PCT/US2012039108
申请日：2012-05-23
申请人： CELL SIGNALING TECHNOLOGY INC , RIMKUNAS VICTORIA MCGUINNESS , HAACK HERBERT , GU TING-LEI , GUO AILAN , POSSEMATO ANTHONY PAUL , CROSBY KATHERINE ELEANOR , TUCKER MEGHAN ANN , REEVES CYNTHIA
发明人： RIMKUNAS VICTORIA MCGUINNESS , HAACK HERBERT , GU TING-LEI , GUO AILAN , POSSEMATO ANTHONY PAUL , CROSBY KATHERINE ELEANOR , TUCKER MEGHAN ANN , REEVES CYNTHIA
IPC分类号： G01N33/574
CPC分类号： G01N33/57423 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , G01N2333/912
摘要： The invention provides the identification of the presence of polypeptides with ROS kinase activity in mammalian lung cancer. In some embodiments, the polypeptide with ROS kinase activity is the result of a fusion between a ROS-encoding polynucleotide and a polynucleotide encoding a second (non-ROS) polypeptide. Three different fusion partners of ROS are described, namely proteins encoded by the FIG gene, the SLC34A2 gene, and the CD74 gene. The invention enables new methods for determining the presence of a polypeptide with ROS kinase activity in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer (e.g., a lung cancer).
摘要翻译：本发明提供在哺乳动物肺癌中鉴定存在具有ROS激酶活性的多肽。在一些实施方案中，具有ROS激酶活性的多肽是编码ROS编码多核苷酸和编码第二（非ROS）多肽的多核苷酸之间融合的结果。描述了ROS的三种不同的融合配偶体，即由FIG基因编码的蛋白质，SLC34A2基因和CD74基因。本发明使得能够测定生物样品中具有ROS激酶活性的多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制癌症进展的方法（例如肺癌）。

2. 发明申请

WO2010093928A3 MUTANT ROS EXPRESSION IN HUMAN CANCER 审中-公开
标题翻译：人类癌症中的突变ROS表达
公开(公告)号：WO2010093928A3
公开(公告)日：2010-11-18
申请号：PCT/US2010024109
申请日：2010-02-12
申请人： CELL SIGNALING TECHNOLOGY INC , GU TING-LEI , TUCKER MEGHAN ANN , HAACK HERBERT , CROSBY KATHERINE ELEANOR , RIMKUNAS VICTORIA MCGUINNESS
发明人： GU TING-LEI , TUCKER MEGHAN ANN , HAACK HERBERT , CROSBY KATHERINE ELEANOR , RIMKUNAS VICTORIA MCGUINNESS
IPC分类号： C07K14/00
CPC分类号： A61K31/506 , A61K31/4545 , C12Q1/6827 , C12Q1/6858 , C12Q1/6869 , C12Q1/6886 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N33/57484 , G01N2333/9121 , G01N2800/52
摘要： The invention provides the identification of the presence of mutant ROS protein in human cancer. In some embodiments, the mutant ROS are FIG-ROS fusion proteins comprising part of the FIG protein fused to the kinase domain of the ROS kinase. In some embodiments, the mutant ROS is the overexpression of wild-type ROS in cancerous tissues (or tissues suspected of being cancerous) where, in normal tissue of that same tissue type, ROS is not expressed or is expressed at lower levels. The mutant ROS proteins of the invention are anticipated to drive the proliferation and survival of a subgroup of human cancers, particularly in cancers of the liver (including bile duct), pancreas, kidney, and testes. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS polypeptides (e.g., a FIG-ROS(S) fusion polypeptide), probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The identification of the mutant ROS polypeptides enables new methods for determining the presence of these mutant ROS polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译：本发明提供了人类癌症中突变型ROS蛋白的存在的鉴定。在一些实施方案中，突变体ROS是包含与ROS激酶的激酶结构域融合的FIG蛋白的部分的FIG-ROS融合蛋白。在一些实施方案中，突变体ROS是野生型ROS在癌组织（或怀疑是癌性的组织）中的过表达，其中在相同组织类型的正常组织中ROS不被表达或以较低水平表达。预期本发明的突变体ROS蛋白质可以驱动人类癌症亚群的增殖和存活，特别是在肝脏（包括胆管），胰腺，肾脏和睾丸癌。因此，本发明部分地提供了分离的多核苷酸和编码所公开的突变型ROS多肽的载体（例如，FIG-ROS（S）融合多肽），用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合的试剂和截短的多肽。鉴定突变体ROS多肽使得能够确定生物样品中这些突变型ROS多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制以突变体多核苷酸或多肽为特征的癌症进展的方法，其也由本发明提供。

3. 发明申请

WO2011146945A3 ALK AND ROS KINASE IN CANCER 审中-公开
标题翻译：癌症中的ALK和ROS激酶
公开(公告)号：WO2011146945A3
公开(公告)日：2012-01-12
申请号：PCT/US2011037622
申请日：2011-05-23
申请人： CELL SIGNALING TECHNOLOGY INC , RIMKUNAS VICTORIA MCGUINNESS , HAACK HERBERT , CROSBY KATHERINE ELEANOR , WILKER NANCY CHIU
发明人： RIMKUNAS VICTORIA MCGUINNESS , HAACK HERBERT , CROSBY KATHERINE ELEANOR , WILKER NANCY CHIU
IPC分类号： C12Q1/68 , G01N33/53 , G01N33/574
CPC分类号： C12Q1/6886 , C07K16/40 , C12Q1/485 , C12Q2600/106 , C12Q2600/136 , G01N33/57484 , G01N2333/71
摘要： A method for identifying a patient with cancer or suspected of having cancer as a patient likely to respond to an ALK- and/or ROS- inhibiting therapeutic is provided, the method comprising: contacting a biological sample from a patient with a first reagent that specifically binds a polypeptide having ROS kinase activity and a second reagent that specifically binds to a polypeptide having ALK knase activity, and detecting whether the first reagent or the second reagent specifically binds to the biological sample, wherein detection of binding of either the first reagent or the second reagent to the biological sample identifies the patient as a patient likely to respond to an ALK-inhibiting and/or ROS-inhibiting therapeutic.
摘要翻译：提供了一种用于鉴定患有癌症或怀疑具有癌症的患者作为可能对ALK和/或ROS抑制治疗剂有反应的患者的方法，所述方法包括：使来自患者的生物样品与特异性的第一试剂接触结合具有ROS激酶活性的多肽和特异性结合具有ALK knase活性的多肽的第二试剂，以及检测第一试剂或第二试剂是否特异性结合生物样品，其中检测第一试剂或生物样品的第二试剂将患者识别为可能对ALK抑制和/或ROS抑制治疗剂有反应的患者。

4. 发明申请

WO2012019132A3 ANAPLASTIC LYMPHOMA KINASE IN KIDNEY CANCER 审中-公开
标题翻译：肾癌中的增生性淋巴瘤激酶
公开(公告)号：WO2012019132A3
公开(公告)日：2012-03-29
申请号：PCT/US2011046807
申请日：2011-08-05
申请人： CELL SIGNALING TECHNOLOGY INC , HAACK HERBERT , CROSBY KATHERINE ELEANOR , RIMKUNAS VICTORIA MCGUINNESS , SILVER MATTHEW REN
发明人： HAACK HERBERT , CROSBY KATHERINE ELEANOR , RIMKUNAS VICTORIA MCGUINNESS , SILVER MATTHEW REN
IPC分类号： C12Q1/48
CPC分类号： G01N33/57484 , A61K31/4162 , A61K31/4545 , A61K31/517 , C12Q1/6886 , C12Q2600/112 , G01N33/57438 , G01N2333/70596 , G01N2800/52
摘要： The invention provides methods to identify, diagnose, and treat kidney cancer through the detection of expression and/or activity of anaplastic lymphoma kinase (ALK). The detection of the presence of a polypeptide with ALK kinase activity (e.g., by detecting expression and/or activity of the polypeptide), identify those kidney cancers that are likely to respond to an ALK-inhibiting therapeutic.
摘要翻译：本发明提供了通过检测间变性淋巴瘤激酶（ALK）的表达和/或活性来鉴定，诊断和治疗肾癌的方法。检测具有ALK激酶活性的多肽（例如通过检测多肽的表达和/或活性）的存在，鉴定可能对ALK抑制性治疗剂有反应的那些肾癌。

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