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公开(公告)号：EP2758778A1
公开(公告)日：2014-07-30
申请号：EP12833527.0
申请日：2012-09-21
CPC分类号： C12Q1/6883 , C07K14/4705 , G01N33/5088 , G01N33/6893 , G01N33/6896 , G01N2333/4706 , G01N2500/00 , G01N2800/30 , G01N2800/302 , G01N2800/50 , G01N2800/52
摘要： The present invention provides a method of screening a mammal for the onset or predisposition to the onset of a neuropsychiatric disorder. More particularly, the present invention provides a method of screening a mammal for the onset or predisposition to the onset of schizophrenia by screening for a decrease in the functional level of protein 1 4-3-3ζ. In a related aspect, the present invention also provides a means of monitoring a patient diagnosed with a neuropsychiatric disorder, such as schizophrenia, by screening for changes to functional levels of protein 14-3-3 ζ. This may be useful, for example, in the context of evaluating the effectiveness of a prophylactic or therapeutic treatment regime or otherwise monitoring the impact of physiological or metabolic changes which may occur in a patient. The method of the present invention is useful in a wide range of applications including, inter alia, providing a means of identifying mammals susceptible to the onset of a neuropsychiatric condition, such as a condition characterized by one or more symptoms of schizophrenia, thereby enabling the implementation of prophylactic or early therapeutic intervention in an effort to either minimize or prevent the onset of the condition. It also provides a means of confirming diagnoses which would otherwise be based solely on an assessment of positive and negative symptoms.
摘要翻译： 本发明提供了筛选哺乳动物神经精神障碍发作或易患发病的方法。 更具体地说，本发明提供了通过筛选蛋白14-3-3ζ的功能水平降低来筛选哺乳动物发病或易患精神分裂症的方法。 在相关方面，本发明还提供了通过筛选蛋白质14-3-3ζ的功能水平的变化来监测被诊断患有神经精神病症例如精神分裂症的患者的手段。 例如，在评估预防性或治疗性治疗方案的有效性或另外监测患者中可能发生的生理或代谢变化的影响的情况下，这可能是有用的。 本发明的方法可用于广泛的应用，尤其包括提供鉴定易受神经精神病症状发作影响的哺乳动物（例如以精神分裂症的一种或多种症状为特征的病症）的手段， 实施预防性或早期治疗性干预以尽量减少或预防病症的发作。 它还提供了确认诊断的手段，否则这些诊断将仅基于评估正面和负面症状。
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公开(公告)号：EP2341133A1
公开(公告)日：2011-07-06
申请号：EP10186089.8
申请日：2002-10-04
申请人： Novartis AG , Université Victor Segalen Bordeaux 2 , Oregon Health and Science University , Technische Universität München , University of Heidelberg , Centre Hospitalier Regional Universitaire de Lille , MEDVET SCIENCE PTY. LTD.
发明人： Barthe, Christophe , Branford, Susan , Corbin, Amie , Druker, Brian Jay , Duyster, Justus , Hochhaus, Andreas , Hughes, Timothy , Kreil, Sebastian , Leguay, Thibaut , Mahon, Francois-Xavier , Marit, Gerald , Mueller, Martin , Peschel, Christian , Preudhomme, Claude , Roche Lestienne, Catherine , Rudzki, Zbigniew
CPC分类号： C12N9/1205
摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, IIe313, Phe317, Met318, Met351, Glu355, Glu359, IIe360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.
摘要翻译： 本发明涉及分离的多肽，其包含功能激酶结构域，所述功能激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本上相似的序列，其中至少一个选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，IIe313，Phe317，Met318，Met351，Glu355，Glu359，IIe360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一氨基酸取代，所述突变的功能性激酶结构域是抗性 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 涉及使用这样的多肽筛选抑制这些多肽的酪氨酸激酶活性的化合物，编码这些多肽的核酸分子，包含这些核酸分子的重组载体和宿主细胞，以及涉及这样的多肽 核酸分子 用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。
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公开(公告)号：EP1290182B1
公开(公告)日：2010-12-22
申请号：EP01929118.6
申请日：2001-05-11
发明人： VADAS, Mathew , GAMBLE, Jennifer , XIA, Pu , WANG, Lijun
IPC分类号： A61K31/133 , A61P35/00
CPC分类号： C12N9/1205 , A61K31/13 , A61K38/00
摘要： The present invention relates generally to a method of modulating the growth of cells and, more particularly, to a method of down-regulating the growth of neoplastic cells. The present invention is useful, inter alia, in the therapeutic and/or prophylactic treatment of cancers such as, but not limited to, solid cancers such as cancers of the colon, stomach, lung, brain, bone, oesophagus, pancreas, breast, ovary or uterus.
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公开(公告)号：EP2246416A1
公开(公告)日：2010-11-03
申请号：EP10155600.9
申请日：2002-10-04
申请人： Novartis AG , Université Victor Segalen Bordeaux 2 , Oregon Health and Science University , Technische Universität München , University of Heidelberg , Centre Hospitalier Regional Universitaire de Lille , MEDVET SCIENCE PTY. LTD.
发明人： Barthe, Christophe , Branford, Susan , Corbin, Amie , Druker, Brian Jay , Duyster, Justus , Hochhaus, Andreas , Hughes, Timothy , Kreil, Sebastain , Leguay, Thibaut , Mahon, Francois-Xavier , Marit, Gerald , Mueller, Martin , Peschel, Christian , Preudhomme, Claude , Roche Lestienne, Christine , Rudzki, Zbigniew
CPC分类号： C12N9/1205
摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-yl m ethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.
摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，其包含天然人类Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基m乙基）对其酪氨酸激酶活性的抑制， 苯甲酰胺或其盐，使用这种多肽来筛选抑制这些多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含该核酸分子的宿主细胞，以及使用 的这种核酸痣 制备此类多肽的细胞用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。
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65.发明公开METHOD FOR OPTIMIZING THE TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH ABL TYROSINE KINASE INHIBITORS 审中-公开优化ABL酪氨酸激酶抑制剂治疗慢性髓细胞白血病的方法
公开(公告)号：EP2170336A4
公开(公告)日：2010-07-07
申请号：EP08756991
申请日：2008-06-20
IPC分类号： A61K31/506 , A61P35/02 , G01N33/60
CPC分类号： A61K31/506
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66.发明公开METHOD FOR OPTIMIZING THE TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH ABL TYROSINE KINASE INHIBITORS 审中-公开用于优化治疗白血病WITH ABL慢性髓细胞性酪氨酸激酶抑制剂
公开(公告)号：EP2170336A1
公开(公告)日：2010-04-07
申请号：EP08756991.9
申请日：2008-06-20
IPC分类号： A61K31/506 , A61P35/02 , G01N33/60
CPC分类号： A61K31/506
摘要： The present invention relates to a method for evaluating patients to help optimizing the treatment of chronic myeloid leukemia (CML) in a human patient population. More specifically, the method comprises the steps of (a) determining the OCT-1 Activity in pre-therapy blood of a warm-blooded animal suffering from CML, and (b) administering a daily dose between about 500 and 1200 mg of Imatinib mesylate to the warm-blooded animal suffering from CML showing an OCT-1 Activity corresponding to Imatinib intracellular concentration below about 6.0 to 10.0 ng/200,000 cells, especially about 8.0 to 8.5 ng/200,000 cells.
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67.发明公开MODULATION OF EGFR SIGNALLING BY MODULATION OF SPHINGOSINE KINASE SIGNALLING 审中-公开EGFR信号由穿梭鞘氨醇信号传导的调节
公开(公告)号：EP1910523A4
公开(公告)日：2009-05-27
申请号：EP06752619
申请日：2006-06-21
发明人： XIA PU , SUKOCHEVA OLGA , VADAS MATHEW ALEXANDER
CPC分类号： C12N15/1137 , A61K48/00 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/3517 , C12Y207/01091
摘要： The present invention relates generally to a method of modulating EGFR-mediated cellular functional activity and agents useful for same. More particularly, the present invention relates to a method of modulating agonist induced EGFR-mediated cellular proliferation by modulating upstream intracellular sphingosine kinase signalling. The method of the invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant EGFR-mediated cellular functioning, in particular aberrant EGFR-mediated cellular proliferation.
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68.发明公开Method of optimizing the treatment of chronic myeloid leukemia with Abl tyrosine kinase inhibitors 审中-公开用于与Abl的Tyroskinkinasehemmern优化慢性粒细胞白血病的治疗方法
公开(公告)号：EP2005961A1
公开(公告)日：2008-12-24
申请号：EP07110868.2
申请日：2007-06-22
IPC分类号： A61K31/506 , A61P35/02
CPC分类号： A61K31/506
摘要： The present invention relates to a method of treating chronic myeloid leukemia (CML) in a human patient population. More specifically, the method comprises the steps of (a) determining the OCT-1 Activity in pre-therapy blood of a warm-blooded animal suffering from CML, and (b) administering a daily dose between about 500 and 1200 mg of Imatinib mesylate to the warm-blooded animal suffering from CML showing an OCT-1 Activity below about 6.0 to 10.0 ng/200,000 cells, especially about 8.0 to 8.5 ng/200,000 cells.
摘要翻译： 本发明涉及在人类患者群中治疗慢性髓性白血病（CML）的方法。 更具体地，该方法包括（a）确定的挖掘中从CML温血动物患有的治疗前血液OCT-1活性的步骤，和（b）施用伊马替尼的大约500和1200毫克之间的每日剂量 从OCT-1活性的CML下面显示约6.0至10.0纳克/ 200,000个细胞的温血动物的痛苦，爱特别是约8.0至8.5纳克/ 200,000个细胞。
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公开(公告)号：EP1910525A1
公开(公告)日：2008-04-16
申请号：EP06752621.0
申请日：2006-06-21
CPC分类号： C12N9/1205 , A61K48/00 , C12Y207/01091
摘要： The present invention relates generally to a method of modulating cellular activity and to agents for use therein. More particularly, the present invention provides a method of modulating the level of sphingosine kinase functional activity. In a related aspect, the present invention provides a method of modulating sphingosine kinase mediated signalling via modulation of its intracellular level of activity. The present invention still further extends to novel molecules which exhibit the capacity to induce sphingosine kinase activity. The methods and molecules of the present invention are useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate cellular functional activity and/or aberrant, unwanted or otherwise inappropriate sphingosine kinase mediated signalling. The present invention is further directed to methods for identifying and/or designing agents capable of modulating the level of sphingosine kinase activity.
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公开(公告)号：EP1910524A1
公开(公告)日：2008-04-16
申请号：EP06752620.2
申请日：2006-06-21
CPC分类号： C12Y207/01091 , A61K48/00 , C12N9/1205
摘要： The present invention relates generally to a method of modulating cellular activity and to agents for use therein. More particularly, the present invention provides a method of modulating the level of sphingosine kinase functional activity. In a related aspect, the present invention provides a method of modulating sphingosine kinase mediated signalling via modulation of its intracellular level of activity. The present invention still further extends to novel molecules which exhibit the capacity to induce sphingosine kinase activity. The methods and molecules of the present invention are useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate cellular functional activity and/or aberrant, unwanted or otherwise inappropriate sphingosine kinase mediated signalling. The present invention is further directed to methods for identifying and/or designing agents capable of modulating the level of sphingosine kinase activity.
摘要翻译： 本发明一般涉及调节细胞活性的方法和用于其中的试剂。 更具体地说，本发明提供了调节鞘氨醇激酶功能活性水平的方法。 在相关方面，本发明提供了通过调节其胞内活性水平来调节鞘氨醇激酶介导的信号传导的方法。 本发明还进一步扩展到表现出诱导鞘氨醇激酶活性的能力的新型分子。 本发明的方法和分子尤其可用于治疗和/或预防以异常的，不需要的或其他不适当的细胞功能活性和/或异常的，不需要的或其他不适当的鞘氨醇激酶介导的信号传导为特征的病症。 本发明还涉及鉴定和/或设计能够调节鞘氨醇激酶活性水平的药剂的方法。
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