首页> 外国专利> isolated polynucleotide, expression cassette, host cell, isolated polypeptide, non-human transgenic animal that has been altered to express an alkali resistant mutant polypeptide, an antibody that specifically binds to an alkali resistant mutant polypeptide, a mutation detection kit alk inhibitor resistance in a biological sample, and methods for evaluating a biological sample for an alk inhibitor resistance mutation to diagnose cancer that is resistant to or likely to develop resistance to at least one alkaline inhibitor. small alk molecule kinase, to evaluate a biological sample for an alk inhibitor resistance mutation, to diagnose cancer that is resistant to or likely to develop resistance to pf-02341066 in a patient, to specifically reduce expression of an alk-resistant mutant to treat cancer associated with activating aberrant loop capacity that is resistant to at least one small molecule alk kinase inhibitor treating an aberrant cancer that is resistant to pf-02341066, identifyin

isolated polynucleotide, expression cassette, host cell, isolated polypeptide, non-human transgenic animal that has been altered to express an alkali resistant mutant polypeptide, an antibody that specifically binds to an alkali resistant mutant polypeptide, a mutation detection kit alk inhibitor resistance in a biological sample, and methods for evaluating a biological sample for an alk inhibitor resistance mutation to diagnose cancer that is resistant to or likely to develop resistance to at least one alkaline inhibitor. small alk molecule kinase, to evaluate a biological sample for an alk inhibitor resistance mutation, to diagnose cancer that is resistant to or likely to develop resistance to pf-02341066 in a patient, to specifically reduce expression of an alk-resistant mutant to treat cancer associated with activating aberrant loop capacity that is resistant to at least one small molecule alk kinase inhibitor treating an aberrant cancer that is resistant to pf-02341066, identifyin

机译:分离的多核苷酸,表达盒,宿主细胞,分离的多肽,已被改变以表达耐碱突变体多肽的非人类转基因动物,与耐碱突变体多肽特异性结合的抗体,突变检测试剂盒生物样品,以及用于评估生物样品中是否存在对烷基抑制剂的抗性突变以诊断对至少一种碱性抑制剂有抗药性或可能发展出抗药性的癌症的方法。小分子激酶,用于评估生物学样品中是否具有抑制碱性磷酸酶抑制剂的突变,以诊断对患者具有抗药性或可能对pf-02341066产生抗药性的癌症,从而特异性降低抗癌突变体的表达以治疗癌症与激活抗至少一种小分子烷基激酶抑制剂的异常环路能力有关,该抑制剂治疗对pf-02341066有抵抗力的异常癌症

摘要

isolated polynucleotide, expression cassette, host cell, isolated polypeptide, non-human transgenic animal that has been altered to express an alkali resistant mutant polypeptide, an antibody that specifically binds to an alkali resistant mutant polypeptide, a mutation detection kit alk inhibitor resistance in a biological sample, and methods for evaluating a biological sample for an alk inhibitor resistance mutation to diagnose cancer that is resistant to or likely to develop resistance to at least one alkaline inhibitor. small alk molecule kinase, to evaluate a biological sample for an alk inhibitor resistance mutation, to diagnose cancer that is resistant to or likely to develop resistance to at least one small alk molecule kinase inhibitor, to evaluate a biological sample for an Aβ inhibitor resistance mutation lk, to diagnose a cancer that is resistant to or likely to develop resistance to pf-02341066 in a patient, to specifically reduce the expression of an alkali resistant mutant, to treat a cancer associated with aberrant alkaline activity that is resistant to at least one small molecule alkaline kinase inhibitor, treating cancer associated with aberrant alkaline activity that is resistant to pf-02341066, identifying an agent capable of inhibiting the kinase activity of a mutant resistant to alk or alk fusion protein. Compositions and methods for diagnosing and treating cancer that is resistant to at least one anaplastic lymphoma kinase (alk) kinase inhibitor are provided herein. The present invention is based on the discovery of mutations within alk that confer resistance to at least one alk inhibitor resistance mutation are provided and find use in methods and compositions useful in the diagnosis, prognosis and / or treatment of diseases associated with activity. aberrant alkali, more particularly those which are resistant to at least one alkaline kinase inhibitor. Methods and compositions are also provided for identifying agents that may inhibit kinase activity and / or reduce the expression level of alk resistance mutants.
机译:分离的多核苷酸,表达盒,宿主细胞,分离的多肽,已被改变以表达耐碱突变体多肽的非人类转基因动物,与耐碱突变体多肽特异性结合的抗体,突变检测试剂盒生物样品,以及用于评估生物样品中是否存在对烷基抑制剂的抗性突变以诊断对至少一种碱性抑制剂有抗药性或可能发展出抗药性的癌症的方法。小烷基分子激酶,以评估生物学样品中是否有抗碱性抑制剂的突变,以诊断对至少一种小烷基分子激酶抑制剂具有抗药性或可能产生抗药性的癌症,以评估生物样品中的Aβ抑制剂抗性突变1k,用于诊断患者对pf-02341066有抗药性或可能发展成对pf-02341066有抗药性的癌症,以特异性降低抗碱性突变体的表达,治疗与对至少一种抗性强的碱性活动有关的癌症小分子碱性激酶抑制剂,用于治疗与耐pf-02341066的异常碱性活性有关的癌症,并鉴定出一种能够抑制对alk或alk融合蛋白有抵抗力的突变体的激酶活性的药物。本文提供了用于诊断和治疗抗至少一种间变性淋巴瘤激酶(alk)激酶抑制剂的癌症的组合物和方法。本发明基于发现烷基内赋予至少一种烷基抑制剂抗性突变的抗性的突变,并发现其可用于诊断,预后和/或治疗与活动有关的疾病的方法和组合物中。异常碱,更特别是对至少一种碱性激酶抑制剂有抗性的那些。还提供了用于鉴定可以抑制激酶活性和/或降低耐碱性突变体的表达水平的试剂的方法和组合物。

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