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1. 发明申请

US20060211060A1 Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors 有权
公开(公告)号：US20060211060A1
公开(公告)日：2006-09-21
申请号：US11377530
申请日：2006-03-16
申请人： John Haley , Graeme Griffin , Lukas Amler , David Eberhard , Robert Yauch
发明人： John Haley , Graeme Griffin , Lukas Amler , David Eberhard , Robert Yauch
IPC分类号： G01N33/574
CPC分类号： A61K31/517 , 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.

2. 发明申请

US20080038271A1 Extending survival of cancer patients with elevated levels of EGF or TGF-alpha 审中-公开
标题翻译：扩大EGF或TGF-α水平升高的癌症患者的生存期
公开(公告)号：US20080038271A1
公开(公告)日：2008-02-14
申请号：US11809666
申请日：2007-05-31
申请人： Lukas Amler , Joachim Moecks , Nusrat Rabbee , Andreas Strauss
发明人： Lukas Amler , Joachim Moecks , Nusrat Rabbee , Andreas Strauss
IPC分类号： A61K39/395 , A61P35/00
CPC分类号： C07K16/32 , A61K39/39558 , A61K45/06 , A61K2039/505 , C07K16/3046 , C07K16/3069 , A61K2300/00
摘要： The present application describes extending survival in a cancer patient, where the patient is producing an elevated level of EGF or TGF-alpha, by treating the patient with a HER dimerization inhibitor, such as pertuzumab.
摘要翻译：本申请描述了通过用HER二聚化抑制剂如珀妥珠单抗治疗患者，在患者产生升高的EGF或TGF-α水平的癌症患者中延长存活。

3. 发明申请

US20060121044A1 Selecting patients for therapy with a her inhibitor 审中-公开
标题翻译：选择患者用她的抑制剂进行治疗
公开(公告)号：US20060121044A1
公开(公告)日：2006-06-08
申请号：US11295229
申请日：2005-12-06
申请人： Lukas Amler , Thomas Januario
发明人： Lukas Amler , Thomas Januario
IPC分类号： C12Q1/68 , A61K39/395
CPC分类号： G01N33/566 , C07K16/32 , C07K2317/24 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N33/5748 , G01N2333/485 , G01N2333/91215
摘要： A method for selecting patients for therapy with a HER inhibitor, such as pertuzumab, based on gene expression analysis is described. A method for assessing HER phosphorylation or activation in a biological sample via gene expression analysis is also described.
摘要翻译：描述了基于基因表达分析选择患者用HER抑制剂如珀妥珠单抗治疗的方法。还描述了通过基因表达分析评估生物样品中的HER磷酸化或活化的方法。

4. 发明申请

US20060234237A1 Biomarkers and methods for determining sensitivity to epidermal growth factor receptor modulators 审中-公开
标题翻译：用于确定对表皮生长因子受体调节剂敏感性的生物标志物和方法
公开(公告)号：US20060234237A1
公开(公告)日：2006-10-19
申请号：US10541749
申请日：2004-01-08
申请人： Lukas Amler , Thomas Januario
发明人： Lukas Amler , Thomas Januario
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： G01N33/57484 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N2333/71 , G01N2800/52
摘要： EGFR biomakers useful in a method for identifying a mammal that will respond therapeutically to a method of treating cancer comprising administering an EGFR modulator, wherein the method comprises (a) exposing the mammal to the EGFR modulator and (b) measuring in the mammal level of at least one biomaker, wherein a difference in the level in at least one biomaker measured in (b) compared to the level of the biomaker in a mammal that has not been exposed to the EGFR modulator indicates that the mammal will respond therapeutically to the method of treating cancer.
摘要翻译： EGFR生物标志物可用于鉴定将对治疗癌症治疗的治疗反应的哺乳动物的方法，其包括施用EGFR调节剂，其中所述方法包括（a）将哺乳动物暴露于EGFR调节剂和（b）至少一种生物制剂，其中在（b）中测量的至少一种生物制剂中的水平的差异与尚未暴露于EGFR调节剂的哺乳动物中的生物制剂的水平相比表明哺乳动物将对该方法进行治疗反应治疗癌症。

5. 发明申请

US20060029944A1 Identification of polynucleotides for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells 有权
标题翻译：鉴定用于预测与乳腺细胞相互作用和/或调节蛋白酪氨酸激酶和/或蛋白酪氨酸激酶途径的化合物的活性的多核苷酸
公开(公告)号：US20060029944A1
公开(公告)日：2006-02-09
申请号：US11072175
申请日：2005-03-04
申请人： Fei Huang , Xia Han , Karen Reeves , Lukas Amler , Craig Fairchild , Francis Lee , Peter Shaw
发明人： Fei Huang , Xia Han , Karen Reeves , Lukas Amler , Craig Fairchild , Francis Lee , Peter Shaw
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C07K14/47 , A61K38/00 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/158
摘要： The present invention describes polynucleotides that have been discovered to correlate to the relative intrinsic sensitivity or resistance of cells, e.g., breast cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit, protein tyrosine kinases, such as, for example, members of the Src family of tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other protein tyrosine kinases, including, Bcr-abl, Jak, PDGFR, c-kit and Eph receptors. These polynucleotides have been shown, through a weighted voting cross validation program, to have utility in predicting the resistance and sensitivity of breast cell lines to the compounds. The expression level or phosphorylation status of some polynucleotides is regulated by treatment with a particular protein tyrosine kinase inhibitor compound, thus indicating that these polynucleotides are involved in the protein tyrosine kinase signal transduction pathway, e.g., Src tyrosine kinase. Such polynucleotides, whose expression levels correlate highly with drug sensitivity or resistance and which are modulated by treatment with the compounds, comprise polynucleotide predictor or marker sets useful in methods of predicting drug response, and as prognostic or diagnostic indicators in disease management, particularly in those disease areas, e.g., breast cancer, in which signaling through the protein tyrosine kinase pathway, such as the Src tyrosine kinase pathway, is involved with the disease process.
摘要翻译：本发明描述了已被发现与多种细胞相关的细胞（例如，乳腺细胞系）与用蛋白酪氨酸激酶相互作用并调节，例如抑制蛋白质酪氨酸激酶（例如，，Src家族酪氨酸激酶的成员，例如Src，Fgr，Fyn，是，Blk，Hck，Lck和Lyn，以及其它蛋白酪氨酸激酶，包括Bcr-abl，Jak，PDGFR，c-kit和 Eph受体。已经通过加权投票交叉验证程序显示了这些多核苷酸可用于预测乳腺细胞系对化合物的抵抗力和敏感性。一些多核苷酸的表达水平或磷酸化状态通过用特定蛋白质酪氨酸激酶抑制剂化合物的处理来调节，从而表明这些多核苷酸参与蛋白酪氨酸激酶信号转导途径，例如Src酪氨酸激酶。这些多核苷酸的表达水平与药物敏感性或抗性高度相关并且通过用化合物处理而被调节的多核苷酸包括用于预测药物反应的方法中的多核苷酸预测物或标志物组，以及疾病管理中的预后或诊断指标，特别是在那些疾病领域，例如乳腺癌，其中通过蛋白酪氨酸激酶途径的信号传导，例如Src酪氨酸激酶途径参与疾病过程。

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