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1. 发明申请

US20090226396A1 Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation 失效
标题翻译：用于鉴定抑制间充质样肿瘤细胞或其形成的药物的方法
公开(公告)号：US20090226396A1
公开(公告)日：2009-09-10
申请号：US12381082
申请日：2009-03-06
申请人： John D. Haley , Stuart Thomson , Julie Kan , Salam A. Shaaban
发明人： John D. Haley , Stuart Thomson , Julie Kan , Salam A. Shaaban
IPC分类号： G01N33/574 , C12Q1/02 , A61K38/20 , A61K38/18 , C12Q1/66 , C12Q1/68 , C12N5/10 , A61P35/00
CPC分类号： G01N33/5011 , G01N2333/475 , G01N2333/485 , G01N2333/495 , G01N2333/525
摘要： The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-1R kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.
摘要翻译：本发明提供用作鉴定抗癌剂的EMT方法的模型的肿瘤细胞制剂，其中所述肿瘤细胞制剂包含受体配体刺激以诱导EMT的上皮肿瘤细胞系H358的细胞，或已被设计成可诱导地表达刺激EMT的蛋白质。本发明还提供了通过使用这样的肿瘤细胞制剂鉴定潜在的抗癌剂的方法来鉴定抑制EMT，刺激MET或抑制间充质细胞生长的药剂。当与其它抗癌药物如EGFR和IGF-1R激酶抑制剂联合使用时，这些药剂应该特别有用，对于抑制已经发生EMT的肿瘤细胞来说，这些药物效果较差。

2. 发明申请

US20080312260A1 Biological markers predictive of anti-cancer response to kinase inhibitors 失效
标题翻译：预测抗癌反应对激酶抑制剂的生物标志物
公开(公告)号：US20080312260A1
公开(公告)日：2008-12-18
申请号：US12082762
申请日：2008-04-14
申请人： John D. Haley , Stuart Thomson
发明人： John D. Haley , Stuart Thomson
IPC分类号： A61K31/517 , C12Q1/02 , A61P35/04
CPC分类号： G01N33/6893 , G01N33/5011 , G01N2333/4712 , G01N2333/4742 , G01N2333/91215
摘要： The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Based on the surprising discovery that tumors cells after having undergone an EMT, while being mesenchymal-like, still express characteristics of both epithelial and mesenchymal cells, and that such cells have altered sensitivity to inhibition by receptor protein-tyrosine kinase inhibitors, in that they have become relatively insensitive to EGFR kinase inhibitors, but have frequently acquired sensitivity to inhibitors of other receptor protein-tyrosine kinases such as PDGFR or FGFR, methods have been devised for determining levels of specific epithelial and mesenchymal biomarkers that identify such “hybrid” tumor cells (e.g. determination of co-expression of vimentin and epithelial keratins), and thus predict the tumor's likely sensitivity to inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Improved methods for treating cancer patients with EGFR, PDGFR or FGFR kinase inhibitors that incorporate such methodology are also provided.
摘要翻译：本发明提供用于预测具有EGFR激酶，PDGFR激酶或FGFR激酶抑制剂的癌症患者治疗有效性的诊断和预后方法。基于令人惊讶的发现，肿瘤细胞在经历EMT之后，同时是间充质的，仍然表现出上皮细胞和间充质细胞的特征，并且这种细胞对受体蛋白 - 酪氨酸激酶抑制剂的抑制具有改变的敏感性，因为它们已经对EGFR激酶抑制剂变得相对不敏感，但是经常获得对其它受体蛋白酪氨酸激酶（例如PDGFR或FGFR）的抑制剂的敏感性，已经设计出用于确定鉴定这种“杂合”肿瘤细胞的特异性上皮和间充质生物标志物的水平的方法（例如测定波形蛋白和上皮角蛋白的共表达），从而预测肿瘤对EGFR激酶，PDGFR激酶或FGFR激酶抑制剂的敏感性。还提供了用于治疗结合这种方法的EGFR，PDGFR或FGFR激酶抑制剂的癌症患者的改进方法。

3. 发明授权

US08383357B2 Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors 失效
标题翻译：预测表皮生长因子受体激酶抑制剂的抗癌反应的生物标志物
公开(公告)号：US08383357B2
公开(公告)日：2013-02-26
申请号：US11787044
申请日：2007-04-13
申请人： John D. Haley , Stuart Thomson , Filippo Petti
发明人： John D. Haley , Stuart Thomson , Filippo Petti
IPC分类号： G01N33/574
CPC分类号： G01N33/6893 , G01N33/5011 , G01N33/57407 , G01N33/57484 , G01N2800/52
摘要： The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.
摘要翻译：本发明提供用于预测EGFR激酶抑制剂治疗癌症患者的有效性的诊断和预后方法。提供了用于预测肿瘤细胞生长对EGFR激酶抑制剂抑制的敏感性的方法，包括通过测定上皮和/或间质生物标志物的表达水平来评估肿瘤细胞是否经历了上皮间质转化（EMT），其中已经经历EMT的肿瘤细胞对EGFR激酶抑制剂的抑制基本上较不敏感。还提供了用于治疗结合上述方法的EGFR激酶抑制剂的癌症患者的改进方法。另外，提供了用于鉴定预测肿瘤对EGFR激酶抑制剂的反应性的新生物标志物的方法。此外，还提供了用于鉴定恢复已经经历EMT的肿瘤细胞对EGFR激酶抑制剂抑制的敏感性的药剂的方法。

4. 发明授权

US07951549B2 Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation 失效
标题翻译：用于鉴定抑制间充质样肿瘤细胞或其形成的药物的方法
公开(公告)号：US07951549B2
公开(公告)日：2011-05-31
申请号：US12381082
申请日：2009-03-06
申请人： John D. Haley , Stuart Thomson , Julie Kan , Salam A. Shaaban
发明人： John D. Haley , Stuart Thomson , Julie Kan , Salam A. Shaaban
IPC分类号： G01N33/574 , C12Q1/02
CPC分类号： G01N33/5011 , G01N2333/475 , G01N2333/485 , G01N2333/495 , G01N2333/525
摘要： The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-1R kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.
摘要翻译：本发明提供用作鉴定抗癌剂的EMT方法的模型的肿瘤细胞制剂，其中所述肿瘤细胞制剂包含受体配体刺激以诱导EMT的上皮肿瘤细胞系H358的细胞，或已被设计成可诱导地表达刺激EMT的蛋白质。本发明还提供了通过使用这样的肿瘤细胞制剂鉴定潜在的抗癌剂的方法来鉴定抑制EMT，刺激MET或抑制间充质细胞生长的药剂。当与其它抗癌药物如EGFR和IGF-1R激酶抑制剂联合使用时，这些药剂应该特别有用，对于抑制已经发生EMT的肿瘤细胞来说，这些药物似乎效果较差。

5. 发明申请

US20050115775A1 Vehicle restraint system 审中-公开
标题翻译：车辆限制系统
公开(公告)号：US20050115775A1
公开(公告)日：2005-06-02
申请号：US10725112
申请日：2003-12-01
申请人： Stuart Thomson , Martin Conneally
发明人： Stuart Thomson , Martin Conneally
IPC分类号： B60T3/00 , B60T1/00
CPC分类号： B60T3/00
摘要： A system for restraining the movement of a vehicle having a wheel with a tire thereon during shipment of the vehicle on a support surface. A chock for engaging at least one of the front or back surfaces of the tire. A strap take-up mechanism engages the support surface and is positioned adjacent the other circumferential surface of the tire. An elongated restraining strap which at one end engages the chock, extends over tire and engages the tire, and at the other end engages the strap take-up mechanism. The strap take-up mechanism includes a pair of legs each engaging the support surface and having a cylindrically shaped, slotted and rotatable hinge pin mounted to the legs for receiving the take-up end of the strap and about which the strap can be wound upon rotation of the cylinder. A handle associated with the cylinder and legs for rotating the cylinder so as to wrap the strap about the cylinder and for securing the cylinder relative to the legs so as to prevent further rotation of the cylinder.
摘要翻译：一种用于在车辆在支撑表面上的运输期间用于限制具有轮胎的车轮在其上的运动的系统。用于接合轮胎的前表面或后表面中的至少一个的轴承座。带子拉紧机构接合支撑表面并且被定位成与轮胎的另一个圆周表面相邻。在一端接合轴承座的细长的限制带在轮胎上延伸并与轮胎接合，并且在另一端接合带卷绕机构。带子卷绕机构包括一对腿，每条腿都与支撑表面接合并且具有安装到腿上的圆柱形，开槽和可旋转的铰链销，用于接收带子的卷绕端，并且带可绕其缠绕气缸旋转。与圆柱体和腿部相关联的手柄，用于旋转圆筒，以使带围绕圆柱体包裹并且用于相对于腿部固定圆柱体，以防止圆筒的进一步旋转。

6. 发明申请

US20050084358A1 Auto parts snugger system 审中-公开
标题翻译：汽车零件紧固系统
公开(公告)号：US20050084358A1
公开(公告)日：2005-04-21
申请号：US10947922
申请日：2004-09-23
申请人： Stuart Thomson , Edward Bell
发明人： Stuart Thomson , Edward Bell
IPC分类号： B60P7/08 , B61D3/16 , B61D45/00
CPC分类号： B60P7/08 , B61D45/001
摘要： A loading restraint and engaging system. The system includes a plurality of rails that are mounted to the side walls of a box car. Each rail is positioned using a locator pin that extends into the car end wall and engages the rail. An end cap or rub rail ramp is provided adjacent the box car door for assisting in moving lading into the car. Wall and floor anchors are provided. Lading restraining nets are provided which engage wall anchors and the end face(s) of the lading.
摘要翻译：装载约束和啮合系统。该系统包括安装在箱车侧壁上的多个轨道。每个导轨使用定位销定位，该定位销延伸到轿厢端壁并接合轨道。在车厢门附近设有端盖或摩擦轨道，用于辅助将货物运送到汽车中。提供墙壁和地板锚。提供了提升的限制网，其接合壁锚和提升的端面。

7. 发明申请

US20050286986A1 Magnetic lading restraining clip 审中-公开
标题翻译：磁珠限制夹
公开(公告)号：US20050286986A1
公开(公告)日：2005-12-29
申请号：US11153306
申请日：2005-06-15
申请人： Stuart Thomson , Roman Poetzel
发明人： Stuart Thomson , Roman Poetzel
IPC分类号： B60P7/08 , B60P7/15 , B61D45/00
CPC分类号： B60P7/0823 , B60P7/15 , B61D45/001
摘要： A clip or hook assembly for use with a pin-like anchor assembly mounted in the side of a railcar for grasping the anchor assembly. The hook is part of a restraining system used to restrain lading loaded and shipped in the railcar. The hook includes a body port having a central aperture for receiving a magnet assembly which can be positioned against the anchor assembly for securing the hook to the anchor and the railcar sidewall.
摘要翻译：一种用于与安装在轨道车辆侧面的销状锚固组件一起使用以夹紧锚固组件的夹子或钩子组件。挂钩是用于限制在轨道车辆中装载和运输的装载的限制系统的一部分。钩包括具有用于接收磁体组件的中心孔的主体端口，磁体组件可以抵靠锚固组件定位，以将钩固定到锚固件和轨道车辆侧壁。

8. 发明申请

US20120302572A1 USE OF EMT GENE SIGNATURES IN CANCER DRUG DISCOVERY, DIAGNOSTICS, AND TREATMENT 有权
标题翻译：在癌症药物发现，诊断和治疗中使用EMT基因标志
公开(公告)号：US20120302572A1
公开(公告)日：2012-11-29
申请号：US13455972
申请日：2012-04-25
申请人： Julie Kan , Stuart Thomson , Gretchen M. Argast , Matthew E. O'Connor , Murray Robinson , Bin Feng , Joerg Heyer , Maria I. Chiu , Richard Nicoletti
发明人： Julie Kan , Stuart Thomson , Gretchen M. Argast , Matthew E. O'Connor , Murray Robinson , Bin Feng , Joerg Heyer , Maria I. Chiu , Richard Nicoletti
IPC分类号： A61K31/517 , A61P35/00 , C40B30/04 , A61K31/4985
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/158
摘要： The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.
摘要翻译：本发明提供用于评估肿瘤细胞的EMT状态的诊断方法，并且利用EMT基因特征指数评分来预测用EGFR或IGF-1R激酶抑制剂治疗癌症患者的有效性。本发明还提供了用于治疗纳入这些方法的癌症患者的方法。

9. 发明申请

US20070110536A1 Corner and bulkhead protector 失效
标题翻译：角和舱壁保护器
公开(公告)号：US20070110536A1
公开(公告)日：2007-05-17
申请号：US10595267
申请日：2004-09-30
申请人： Stuart Thomson , Brian O'Neill
发明人： Stuart Thomson , Brian O'Neill
IPC分类号： B61D45/00
CPC分类号： B60P7/0823 , B60P7/0869 , B61D45/00 , B65D81/055 , B65D2581/055
摘要： A corner protector and bulkhead protector for a cargo carrying vehicle such as a rail car are formed to have deep channels or corrugations that provide for both increased strength and rigidity while also providing support for load restraining web straps.
摘要翻译：形成用于诸如轨道车辆的货物运载车辆的角保护器和隔板保护器，以具有提供增强的强度和刚度的深通道或波纹，同时还为负载限制幅带提供支撑。

10. 发明申请

US20050271490A1 Load restraining device 审中-公开
标题翻译：负载限制装置
公开(公告)号：US20050271490A1
公开(公告)日：2005-12-08
申请号：US11145343
申请日：2005-06-03
申请人： Stuart Thomson , Mark Zhan , Edward Bell
发明人： Stuart Thomson , Mark Zhan , Edward Bell
IPC分类号： B60P7/08 , B60P7/135 , B61D45/00
CPC分类号： B60P7/0876 , B60P7/135 , B61D45/006
摘要： A load restraining device that provides a system in which straps extending from one side of a web strap arrangement initially run parallel to the wall to which they are connected, as opposed to extending perpendicular to the wall as in the prior art. The anchor itself is a horizontal wall member running longitudinally along the wall of the railcar or trailer. An adjustable anchor is used to permit moving the attachment point several inches to allow for load variations. The attachment of the web strap arrangement is normally 14″ to 18″ behind the face of the load. Unlike previous systems, this provision of anchor points behind the load effectively “encapsulates” the load rather than merely providing a bulkhead effect.
摘要翻译：一种负载限制装置，其提供一种系统，其中从卷带装置的一侧延伸的带最初平行于它们所连接的壁延伸，而不是如现有技术那样垂直于壁延伸。锚固件本身是沿着轨道车辆或拖车的壁纵向延伸的水平壁构件。使用可调节锚杆来允许将连接点移动几英寸以允许负载变化。网带装置的连接通常在负载面后面14“至18”。与以前的系统不同，这种在负载后面的锚点的提供有效地“封装”负载，而不仅仅是提供隔板效应。

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