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    • 2. 发明申请
    • Biological markers predictive of anti-cancer response to kinase inhibitors
    • 预测抗癌反应对激酶抑制剂的生物标志物
    • US20080312260A1
    • 2008-12-18
    • US12082762
    • 2008-04-14
    • John D. HaleyStuart Thomson
    • John D. HaleyStuart Thomson
    • A61K31/517C12Q1/02A61P35/04
    • G01N33/6893G01N33/5011G01N2333/4712G01N2333/4742G01N2333/91215
    • 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.
    • 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。
    • 4. 发明申请
    • Load restraining device
    • 负载限制装置
    • US20050271490A1
    • 2005-12-08
    • US11145343
    • 2005-06-03
    • Stuart ThomsonMark ZhanEdward Bell
    • Stuart ThomsonMark ZhanEdward Bell
    • B60P7/08B60P7/135B61D45/00
    • B60P7/0876B60P7/135B61D45/006
    • 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.
    • 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。
    • 7. 发明申请
    • Vehicle restraint system
    • 车辆限制系统
    • US20050115775A1
    • 2005-06-02
    • US10725112
    • 2003-12-01
    • Stuart ThomsonMartin Conneally
    • Stuart ThomsonMartin Conneally
    • B60T3/00B60T1/00
    • B60T3/00
    • 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.
    • 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。
    • 9. 发明授权
    • Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors
    • 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
    • US08383357B2
    • 2013-02-26
    • US11787044
    • 2007-04-13
    • John D. HaleyStuart ThomsonFilippo Petti
    • John D. HaleyStuart ThomsonFilippo Petti
    • G01N33/574
    • G01N33/6893G01N33/5011G01N33/57407G01N33/57484G01N2800/52
    • 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.
    • 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。