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1. 发明申请

WO2007040550A2 TORC POLYNUCLEOTIDES AND POLYPEPTIDES, AND METHODS OF USE 审中-公开
标题翻译： TORC多核苷酸和多肽及其使用方法
公开(公告)号：WO2007040550A2
公开(公告)日：2007-04-12
申请号：PCT/US2005/038207
申请日：2005-10-24
申请人： NOVARTIS AG , NOVARTIS PHARMA GMBH , BITTINGER, Mark , LABOW, Mark, Aron
发明人： BITTINGER, Mark , LABOW, Mark, Aron
IPC分类号： C07K14/435
CPC分类号： C07K14/4705 , A61K38/00 , G01N33/5008 , G01N33/5035 , G01N33/5091 , G01N2333/4706
摘要： The present invention relates to a broad range of methods that utilize a transducer of regulated CREB (TORC)-related polynucleotide, polypeptide, or TORC-specific antibody. In addition the invention relates to TORC-related polynucleotide, polypeptide, or TORC-specific antibody compositions, including variants of TORC wild-type sequences. Exemplary methods include a method of stimulating a TORC related process in a cell as well as a method of inhibiting a TORC-related process in a cell, and a method of inhibiting TORC-related processes in a cell. The invention additionally disclosed therapeutic methods of substantially inhibiting the development of, treating, or ameliorating a disease or pathological condition in a subject related to an abnormal level of a TORC-activated process in a cell that includes administering one or more therapeutically effective doses to the subject of either a substance that modulates accumulation of a TORC polypeptide in a subcellular region of the cell, or of a substance that inhibits expression of a TORC polypeptide in the cell. In an additional aspect a method of identifying an agent that modulates the activity of a TORC-related process in a cell is disclosed. In still a further aspect the invention relates to a method of detecting the presence or quantifying the amount of a TORC polypeptide in a sample. In a further aspect, a method is disclosed of determining whether the amount of a TORC polypeptide in a sample differs from the amount of the TORC polypeptide in a reference. An additional aspect relates to a method of contributing to the diagnosis or prognosis of, or to developing a therapeutic strategy for, a disease or pathology in a first subject, wherein the subcellular localization of a TORC polypeptide in the pathology is known to differ from the subcellular localization of the TORC polypeptide in a nonpathological state.
摘要翻译：本发明涉及利用受调节的CREB（TORC）相关多核苷酸，多肽或TORC特异性抗体的换能器的广泛范围的方法。另外，本发明涉及TORC相关多核苷酸，多肽或TORC特异性抗体组合物，包括TORC野生型序列的变体。示例性方法包括刺激细胞中TORC相关过程的方法以及抑制细胞中TORC相关过程的方法以及抑制细胞中TORC相关过程的方法。本发明另外公开了基本上抑制与细胞中TORC激活过程的异常水平相关的受试者中疾病或病理状态的发展，治疗或改善的治疗方法，所述方法包括对所述受试者施用一种或多种治疗有效剂量受试者是调节TORC多肽在细胞亚细胞区积累的物质或抑制细胞中TORC多肽表达的物质的受试者。在另一方面，公开了鉴定调节细胞中TORC相关过程的活性的试剂的方法。在又一方面，本发明涉及检测样品中TORC多肽的存在或定量的方法。另一方面，公开了确定样品中TORC多肽的量与参考中TORC多肽的量是否不同的方法。另一方面涉及有助于第一受试者的疾病或病理的诊断或预后或制定治疗策略的方法，其中病理学中TORC多肽的亚细胞定位已知不同于 TORC多肽在非病理状态下的亚细胞定位。

2. 发明申请

WO2003069348A3 USE OF MIP-3α AND ITS RECEPTOR TO TREAT ARTHRITIS 审中-公开
公开(公告)号：WO2003069348A3
公开(公告)日：2003-08-21
申请号：PCT/EP2003/001506
申请日：2003-02-14
申请人： NOVARTIS AG , NOVARTIS PHARMA GMBH , KUMAR, Chandrika, Saidapet , LABOW, Mark, Aron , LATARIO, Brian, Jude
发明人： KUMAR, Chandrika, Saidapet , LABOW, Mark, Aron , LATARIO, Brian, Jude
IPC分类号： G01N33/68
摘要： The present invention relates to novel uses for the chemokine MIP-3α and its receptor CCR6 to treat and diagnose osteoarthritis. In particular, MIP-3α is shown to be expressed in cartilage tissue and chondrocytes derived from individuals having osteoarthritis, whereas normally the chemokine is not expressed in such cells or tissues. These findings indicate that both the MIP-3α chemokine and the CCR6 receptor are useful targets, e.g., for the development of therapeutics to treat, ameliorate and/or modulate conditions such as osteoarthritis. Accordingly, the invention provides screening methods for identifying candidate compounds that modulate MIP-3α binding to its receptor and may therefore be used to treat osteoarthritis. Therapeutic methods and pharmaceutical compositions that inhibit MIP-3α expression or activity or, alternatively, inhibit CCR6 expression or activity are also provided. Finally, the invention also provides diagnostic and prognostic methods for identifying individuals having osteoarthritis by detecting MIP-3α expression.

3. 发明申请

WO2004085646A1 CYCLIC AMP RESPONSE ELEMENT ACTIVATOR PROTEINS AND USES RELATED THERETO 审中-公开
标题翻译：循环AMP反应元件激活蛋白及其相关用途
公开(公告)号：WO2004085646A1
公开(公告)日：2004-10-07
申请号：PCT/EP2004/003182
申请日：2004-03-25
申请人： NOVARTIS AG , NOVARTIS PHARMA GMBH , IOURGENKO, Vadim , LABOW, Mark, Aron , SONG, Chuanzheng , ZHANG, Wenjun , ZHU, Jian
发明人： IOURGENKO, Vadim , LABOW, Mark, Aron , SONG, Chuanzheng , ZHANG, Wenjun , ZHU, Jian
IPC分类号： C12N15/12
CPC分类号： A61K38/1709 , C07K14/4705 , C12Q1/6883 , C12Q2600/158 , G01N2500/00
摘要： The invention discloses newly identified cyclic AMP response element activator proteins (CREAP proteins). It is contemplated herein that said proteins are suitable drug targets for the development of new therapeutics to prevent, treat or ameliorate pathological conditions related to abnormal activation of CRE-dependent gene expression or abnormal activation of chemokines. The invention relates to methods to prevent, treat or ameliorate said pathological conditions and pharmaceutical compositions therefor comprising modulators with inhibitory effect on CREAP protein activity and/or CREAP gene expression. The invention also relates to methods to identify compounds with therapeutic usefulness to treat said pathological conditions, comprising identifying compounds that can inhibit CREAP protein activity and/or CREAP gene expression.
摘要翻译：本发明公开了新鉴定的环AMP应答元件活化蛋白（CREAP蛋白）。本文预期所述蛋白质是用于开发新的治疗剂以预防，治疗或改善与CRE依赖性基因表达异常活化或趋化因子异常激活相关的病理状况的合适药物靶标。本发明涉及预防，治疗或改善所述病理状态的方法及其药物组合物，其包含对CREAP蛋白活性和/或CREAP基因表达具有抑制作用的调节剂。本发明还涉及鉴定具有治疗所述病理状况的治疗有效性的化合物的方法，其包括鉴定能抑制CREAP蛋白活性和/或CREAP基因表达的化合物。

4. 发明申请

WO2006044366A2 E2-EPF5, A NOVEL THERAPEUTIC PROTEIN AND TARGET 审中-公开
标题翻译： E2-EPF5，一种新的治疗蛋白和目标
公开(公告)号：WO2006044366A2
公开(公告)日：2006-04-27
申请号：PCT/US2005/036505
申请日：2005-10-12
申请人： NOVARTIS AG , NOVARTIS PHARMA GmbH , ASSELBERGS, Fred, A. , HALL, Jonathan , HUESKEN, Dieter , LABOW, Mark, Aron , MICKANIN, Craig, Stephen , SCHMID, Peter , WEILER, Jan , WYDER, Lorenza
发明人： ASSELBERGS, Fred, A. , HALL, Jonathan , HUESKEN, Dieter , LABOW, Mark, Aron , MICKANIN, Craig, Stephen , SCHMID, Peter , WEILER, Jan , WYDER, Lorenza
CPC分类号： C12N15/1137 , C07K16/40 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12Y603/02019 , C12N2310/3525
摘要： The present invention relates to novel uses for ubiquitin conjugating enzyme E2-EPF5. In particular, inhibition of E2-EPF5 activity is shown to reduce the production VEGF, as well as other proteins regulated the transcription factor HIF-1, in response to hypoxia. Based on these findings the present invention provides therapeutic methods and pharmaceutical compositions useful for the treatment of diseases related VEGF induced angiogenesis. In addition, E2-EPF5 is provided as target for the development of therapeutics. Accordingly, the invention provides screening methods for identifying candidate compounds that inhibit E2-EPF5 activity and may therefore be used to treat VEGF induced angiogenesis such as tumor related angiogenesis. Finally, the invention also provides methods for the inhibition of VEGF and other HIF-1 regulated proteins.
摘要翻译：本发明涉及泛素缀合酶E2-EPF5的新用途。特别地，E2-EPF5活性的抑制显示可以减少VEGF的产生，以及调节转录因子HIF-1的其他蛋白质，以应对缺氧。基于这些发现，本发明提供治疗方法和药物组合物，其可用于治疗涉及VEGF诱导的血管发生的疾病。此外，提供E2-EPF5作为治疗开发的目标。因此，本发明提供用于鉴定抑制E2-EPF5活性的候选化合物的筛选方法，因此可用于治疗VEGF诱导的血管生成如肿瘤相关的血管发生。最后，本发明还提供了抑制VEGF和其他HIF-1调节蛋白的方法。

5. 发明申请

WO2003069348A2 USE OF MIP-3α AND ITS RECEPTOR TO TREAT ARTHRITIS 审中-公开
标题翻译：使用MIP-3α及其受体治疗ARTHRITIS
公开(公告)号：WO2003069348A2
公开(公告)日：2003-08-21
申请号：PCT/EP2003/001506
申请日：2003-02-14
申请人： NOVARTIS AG , NOVARTIS PHARMA GMBH , KUMAR, Chandrika, Saidapet , LABOW, Mark, Aron , LATARIO, Brian, Jude
发明人： KUMAR, Chandrika, Saidapet , LABOW, Mark, Aron , LATARIO, Brian, Jude
IPC分类号： G01N33/68
CPC分类号： C12Q1/6883 , C12Q2600/158 , G01N33/6863 , G01N2500/02
摘要： The present invention relates to novel uses for the chemokine MIP-3α and its receptor CCR6 to treat and diagnose osteoarthritis. In particular, MIP-3α is shown to be expressed in cartilage tissue and chondrocytes derived from individuals having osteoarthritis, whereas normally the chemokine is not expressed in such cells or tissues. These findings indicate that both the MIP-3α chemokine and the CCR6 receptor are useful targets, e.g., for the development of therapeutics to treat, ameliorate and/or modulate conditions such as osteoarthritis. Accordingly, the invention provides screening methods for identifying candidate compounds that modulate MIP-3α binding to its receptor and may therefore be used to treat osteoarthritis. Therapeutic methods and pharmaceutical compositions that inhibit MIP-3α expression or activity or, alternatively, inhibit CCR6 expression or activity are also provided. Finally, the invention also provides diagnostic and prognostic methods for identifying individuals having osteoarthritis by detecting MIP-3α expression.
摘要翻译：本发明涉及趋化因子MIP-3α及其受体CCR6治疗和诊断骨关节炎的新用途。特别地，MIP-3α显示在软骨组织中表达，软骨细胞衍生自具有骨关节炎的个体，而通常在这些细胞或组织中不表达趋化因子。这些发现表明，MIP-3α趋化因子和CCR6受体都是有用的靶标，例如用于开发治疗，改善和/或调节诸如骨关节炎的病症的治疗剂。因此，本发明提供了用于鉴定调节MIP-3α与其受体结合的候选化合物的筛选方法，因此可用于治疗骨关节炎。还提供了抑制MIP-3α表达或活性或抑制CCR6表达或活性的治疗方法和药物组合物。最后，本发明还提供了通过检测MIP-3α表达来鉴定患有骨关节炎的个体的诊断和预后方法。

6. 发明申请

WO2008057172A3 ORGANIC COMPOUNDS 审中-公开
公开(公告)号：WO2008057172A3
公开(公告)日：2008-05-15
申请号：PCT/US2007/022125
申请日：2007-10-17
申请人： NOVARTIS AG , GAITHER, Larry, Alexander , IOURGENKO, Vadim , LABOW, Mark, Aron , PORTER, Dale, Alan , STRAUB, Christopher, Sean , YAO, Yao , ZAWEL, Leigh
发明人： GAITHER, Larry, Alexander , IOURGENKO, Vadim , LABOW, Mark, Aron , PORTER, Dale, Alan , STRAUB, Christopher, Sean , YAO, Yao , ZAWEL, Leigh
IPC分类号： G01N33/574 , G01N33/68
摘要： A method to predict which patients will respond to a IAP inhibiting compound comprising: a) administering an IAP inhibitor compound to a patient, and b) measuring TNF-α or IL-8 levels.

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