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1. 发明申请

WO2007089367A3 USE HEDGEHOG KINASE ANTAGONISTS TO INHIBIT HEDGEHOG SIGNALING AND TO TREAT CANCER 审中-公开
标题翻译：使用HEDGEHOG激酶拮抗剂抑制HEDGEHOG信号和治疗癌症
公开(公告)号：WO2007089367A3
公开(公告)日：2008-10-09
申请号：PCT/US2006062052
申请日：2006-12-13
申请人： GENENTECH INC , CURIS INC , DE SAUVAGE FREDERIC J , EVANGELISTA MARIE
发明人： DE SAUVAGE FREDERIC J , EVANGELISTA MARIE
IPC分类号： A61K31/7088 , A61K47/48 , A61P35/00 , C12N5/00 , C12N15/113 , G01N33/50
CPC分类号： C12Q1/485 , A61K31/7088 , A61K38/45 , A61K47/54 , A61K47/56 , A61K47/62 , A61K47/6803 , A61K47/6809 , A61K47/6811 , A61K47/6843 , A61K48/00 , C07K16/40 , C12N15/1137 , C12N2310/14 , C12N2310/351 , C12Y207/11 , C12Y207/12001 , G01N33/5011 , G01N33/5058 , G01N33/574 , G01N33/6893 , G01N2800/10 , G01N2800/12 , G01N2800/20 , G01N2800/28 , A61K2300/00
摘要： The present invention provides for a method of using CDC2L1, CSNK1A1, GYK, NEK1, PLK1, PRKAR1A, PRKRA, TTBK2 or TTK hedgehog kinase antagonists to inhibit hedgehog signaling, as well as treating and diagnosing disorders relating to hedgehog signaling or overexpression of hedgehog, including cancer, cell proliferative disorders, and angiogenesis, neurological disorders, as well as other conditions affected by hedgehog signaling such as hair growth, neural stem cell differentiation, chondrogenesis and osteogenesis, lung surfactant production, formation of lamellated bodies in lung cells.
摘要翻译：本发明提供了使用CDC2L1，CSNK1A1，GYK，NEK1，PLK1，PRKAR1A，PRKRA，TTBK2或TTK hedgehog激酶拮抗剂抑制刺猬蛋白信号传导的方法，以及治疗和诊断与刺猬蛋白信号传导或刺猬过度表达相关的疾病，包括癌症，细胞增殖性疾病和血管发生，神经障碍，以及受刺猬蛋白信号传导如毛发生长，神经干细胞分化，软骨形成和成骨，肺表面活性物质生成，肺细胞中层状体形成的其他病症。

2. 发明申请

WO2012047968A2 MUTANT SMOOTHENED AND METHODS OF USING THE SAME 审中-公开
标题翻译： MUTANT SMOOTHENED及其使用方法
公开(公告)号：WO2012047968A2
公开(公告)日：2012-04-12
申请号：PCT/US2011054877
申请日：2011-10-05
申请人： GENENTECH INC , CURIS INC , DE SAUVAGE FREDERIC J
发明人： DE SAUVAGE FREDERIC J
IPC分类号： C07K14/705 , C12Q1/68
CPC分类号： C07K14/705 , C07K14/723
摘要： The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, we describe a mutation in the serpentine receptor, Smoothened (SMO), which results in resistance to a Hedgehog (Hh) pathway inhibitor in medulloblastoma. A single amino acid substitution in a conserved glutamic acid residue of SMO maintains Hh signaling, but results in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. The invention provides screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
摘要翻译：在分子靶向治疗癌症患者治疗后，酪氨酸激酶突变的出现代表了获得性耐药性的主要机制。在这里，我们描述了蛇纹石受体Smoothened（SMO）中的突变，其导致对成神经管细胞瘤中的Hedgehog（Hh）通路抑制剂的抗性。 SMO的保守谷氨酸残基中单个氨基酸取代保持Hh信号传导，但导致Hh通路抑制剂GDC-0449不能结合SMO并抑制途径。本发明提供了检测SMO突变的筛选方法和筛选特异性调节显示耐药性的突变SMO的药物的方法。

3. 发明申请

WO2011028950A1 MUTANT SMOOTHENED AND METHODS OF USING THE SAME 审中-公开
标题翻译： MUTANT SMOOTHENED及其使用方法
公开(公告)号：WO2011028950A1
公开(公告)日：2011-03-10
申请号：PCT/US2010/047739
申请日：2010-09-02
申请人： GENENTECH, INC. , F. HOFFMANN-LA ROCHE AG , DE SAUVAGE, Frederic J. , DIJKGRAAF, Gerrit J. P. , JANUARIO, Thomas , YAUCH, Robert L.
发明人： DE SAUVAGE, Frederic J. , DIJKGRAAF, Gerrit J. P. , JANUARIO, Thomas , YAUCH, Robert L.
IPC分类号： C07K14/705
CPC分类号： G01N33/74 , C07K14/705 , G01N2333/726 , G01N2500/10
摘要： The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, we describe a mutation in the serpentine receptor, Smoothened (SMO), which results in resistance to a Hedgehog (Hh) pathway inhibitor in medulloblastoma. A single amino acid substitution in a conserved aspartic acid residue of SMO maintains Hh signaling, but results in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. This mutation was not only acquired in a GDC-0449-resistant mouse model of medulloblastoma, but was identified in a medulloblastoma patient following relapse on GDC-0449. The invention provides screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
摘要翻译：在分子靶向治疗癌症患者治疗后，酪氨酸激酶突变的出现代表了获得性耐药性的主要机制。在这里，我们描述了蛇纹石受体Smoothened（SMO）中的突变，其导致对成神经管细胞瘤中的Hedgehog（Hh）通路抑制剂的抗性。 SMO的保守天冬氨酸残基中的单个氨基酸取代保持Hh信号传导，但导致Hh途径抑制剂GDC-0449不能结合SMO并抑制途径。该突变不仅在成神经管细胞瘤的GDC-0449抗性小鼠模型中获得，而且在GDC-0449复发后在成神经管细胞瘤患者中鉴定。本发明提供了检测SMO突变的筛选方法和筛选特异性调节显示耐药性的突变SMO的药物的方法。

4. 发明申请

WO2006068822A1 NOTCH RECEPTOR AGONISTS AND USES 审中-公开
标题翻译： NOTCH受体激动剂和用途
公开(公告)号：WO2006068822A1
公开(公告)日：2006-06-29
申请号：PCT/US2005/044123
申请日：2005-12-07
申请人： GENENTECH, INC. , DE SAUVAGE, Frederic, J. , GAO, Wei-Qiang , LEOW, Ching Ching , WANG, Xi-de , ZHA, Jiping
发明人： DE SAUVAGE, Frederic, J. , GAO, Wei-Qiang , LEOW, Ching Ching , WANG, Xi-de , ZHA, Jiping
IPC分类号： A61K38/17 , A61K39/395 , A61P13/08 , C12Q1/68 , G01N33/574
CPC分类号： C07K16/28 , A61K38/1703 , C07K2319/30 , C12Q1/6886 , C12Q2600/136 , G01N33/5008 , G01N33/5011 , G01N33/5044 , G01N33/57434 , G01N33/68 , G01N2500/00
摘要： The present invention is directed to methods of alleviating prostate disorders by activation of the Notch 1 receptor. Also provided herein are methods for detecting and diagnosing prostate disorders, wherein the specific disorder is prostate cancer.
摘要翻译：本发明涉及通过Notch1受体活化来减轻前列腺障碍的方法。本文还提供了用于检测和诊断前列腺疾病的方法，其中特异性病症是前列腺癌。

5. 发明申请

WO2012047968A3 MUTANT SMOOTHENED AND METHODS OF USING THE SAME 审中-公开
公开(公告)号：WO2012047968A3
公开(公告)日：2012-04-12
申请号：PCT/US2011/054877
申请日：2011-10-05
申请人： GENENTECH, INC. , CURIS, INC. , DE SAUVAGE, Frederic J.
发明人： DE SAUVAGE, Frederic J.
IPC分类号： C07K14/705 , C12Q1/68
摘要： The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, we describe a mutation in the serpentine receptor, Smoothened (SMO), which results in resistance to a Hedgehog (Hh) pathway inhibitor in medulloblastoma. A single amino acid substitution in a conserved glutamic acid residue of SMO maintains Hh signaling, but results in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. The invention provides screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.

6. 发明申请

WO2009062102A2 COMPOSITIONS AND METHODS FOR TREATMENT OF MICROBIAL DISORDERS 审中-公开
标题翻译：用于治疗微生物病症的组合物和方法
公开(公告)号：WO2009062102A2
公开(公告)日：2009-05-14
申请号：PCT/US2008082890
申请日：2008-11-07
申请人： GENENTECH INC , ABBAS ALEXANDER R , DANILENKO DIMITRY M , DE SAUVAGE FREDERIC J , GHILARDI NICO P , MODRUSAN ZORA , OUYANG WENJUN , VALDEZ PATRICIA A , ZHENG YAN
发明人： ABBAS ALEXANDER R , DANILENKO DIMITRY M , DE SAUVAGE FREDERIC J , GHILARDI NICO P , MODRUSAN ZORA , OUYANG WENJUN , VALDEZ PATRICIA A , ZHENG YAN
IPC分类号： A61K38/20
CPC分类号： A61K38/191 , A61K38/1709 , A61K38/20 , A61K38/204
摘要： The present invention relates to compositions and methods for treatment of microbial disorder by modulation of the host immune response. More particularly, the present invention relates to compositions that mediate an anti-microbial immune response, and methods of treating a microbial infection using such compositions.
摘要翻译：本发明涉及通过调节宿主免疫应答来治疗微生物病症的组合物和方法。更具体地说，本发明涉及介导抗微生物免疫应答的组合物，以及使用这种组合物治疗微生物感染的方法。

7. 发明申请

WO1997024440A1 OB PROTEIN DERIVATIVES HAVING PROLONGED HALF-LIFE 审中-公开
标题翻译：具有延长半衰期的OB蛋白衍生物
公开(公告)号：WO1997024440A1
公开(公告)日：1997-07-10
申请号：PCT/US1996020718
申请日：1996-12-19
申请人： GENENTECH, INC. , DE SAUVAGE, Frederic, J. , LEVIN, Nancy , VANDLEN, Richard, L.
发明人： GENENTECH, INC.
IPC分类号： C12N15/16
CPC分类号： C07K14/5759 , A61K38/00 , C07K2319/00
摘要： The present invention concerns long half-life derivative of the obesity protein OB. The invention specifically concerns OB protein-immunoglobulin chimeras and polyethylene glycol (PEG)-OB derivatives, which have extended half-life as compared to the corresponding native OB proteins. The invention further relates to methods for appetite and/or weight reduction and for treating other physiological conditions by using the long half-life derivatives of OB.
摘要翻译：本发明涉及肥胖蛋白质OB的长半衰期衍生物。本发明特别涉及与相应的天然OB蛋白相比延长半衰期的OB蛋白 - 免疫球蛋白嵌合体和聚乙二醇（PEG）-OB衍生物。本发明还涉及通过使用OB的长半衰期衍生物来控制食欲和/或体重减轻的方法和用于治疗其它生理状况的方法。

8. 发明申请

WO2009062102A3 COMPOSITIONS AND METHODS FOR TREATMENT OF MICROBIAL DISORDERS 审中-公开
公开(公告)号：WO2009062102A3
公开(公告)日：2009-05-14
申请号：PCT/US2008/082890
申请日：2008-11-07
申请人： GENENTECH, INC. , ABBAS, Alexander, R. , DANILENKO, Dimitry, M. , DE SAUVAGE, Frederic, J. , GHILARDI, Nico, P. , MODRUSAN, Zora , OUYANG, Wenjun , VALDEZ, Patricia, A. , ZHENG, Yan
发明人： ABBAS, Alexander, R. , DANILENKO, Dimitry, M. , DE SAUVAGE, Frederic, J. , GHILARDI, Nico, P. , MODRUSAN, Zora , OUYANG, Wenjun , VALDEZ, Patricia, A. , ZHENG, Yan
IPC分类号： A61K38/20 , A61K38/16 , A61P31/00
摘要： The present invention relates to compositions and methods for treatment of microbial disorder by modulation of the host immune response. More particularly, the present invention relates to compositions that mediate an anti-microbial immune response, and methods of treating a microbial infection using such compositions.

9. 发明申请

WO2007126455A3 METHOD FOR USING BOC/CDO TO MODULATE HEDGEHOG SIGNALING 审中-公开
标题翻译：使用BOC / CDO调制HEDGEHOG信号的方法
公开(公告)号：WO2007126455A3
公开(公告)日：2008-01-03
申请号：PCT/US2007001794
申请日：2007-01-22
申请人： GENENTECH INC , DE SAUVAGE FREDERIC J , TIAN HUA
发明人： DE SAUVAGE FREDERIC J , TIAN HUA
IPC分类号： A61K45/00 , A61K38/17 , A61K39/395 , A61P35/00 , G01N33/50
CPC分类号： G01N33/57484 , A61K38/1774 , A61K47/6809 , A61K47/6817 , A61K47/6849 , A61K47/6899 , A61K47/6913 , B82Y5/00
摘要： The present invention provides for a method of using BOC/CDO hedgehog antagonists to inhibit hedgehog signaling, as well as treating and diagnosing disorders relating to hedgehog signaling or overexpression of hedgehog, including cancer, cell proliferative disorders, and angiogenesis, neurological disorders, as well as other conditions affected by hedgehog signaling such as hair growth, neural stem cell differentiation, chondrogenesis and osteogenesis, lung surfactant production, formation of lamellated bodies in lung cells.
摘要翻译：本发明提供了使用BOC / CDO刺猬蛋白拮抗剂抑制刺猬蛋白信号传导的方法，以及治疗和诊断与刺猬蛋白信号传导或过度表达刺猬的疾病，包括癌症，细胞增殖性疾病和血管发生，神经障碍，以及作为受刺猬信号传导影响的其他条件，如毛发生长，神经干细胞分化，软骨形成和成骨，肺表面活性物质生成，肺细胞中层状体的形成。

10. 发明申请

WO2007126455A2 METHOD FOR USING BOC/CDO TO MODULATE HEDGEHOG SIGNALING 审中-公开
标题翻译：使用BOC / CDO调制HEDGEHOG信号的方法
公开(公告)号：WO2007126455A2
公开(公告)日：2007-11-08
申请号：PCT/US2007/001794
申请日：2007-01-22
申请人： GENENTECH, INC. , DE SAUVAGE, Frederic, J. , TIAN, Hua
发明人： DE SAUVAGE, Frederic, J. , TIAN, Hua
IPC分类号： A61K45/00 , A61K38/17 , A61K39/395 , A61P35/00 , G01N33/50
CPC分类号： G01N33/57484 , A61K38/1774 , A61K47/6809 , A61K47/6817 , A61K47/6849 , A61K47/6899 , A61K47/6913 , B82Y5/00
摘要： The present invention provides for a method of using BOC/CDO hedgehog antagonists to inhibit hedgehog signaling, as well as treating and diagnosing disorders relating to hedgehog signaling or overexpression of hedgehog, including cancer, cell proliferative disorders, and angiogenesis, neurological disorders, as well as other conditions affected by hedgehog signaling such as hair growth, neural stem cell differentiation, chondrogenesis and osteogenesis, lung surfactant production, formation of lamellated bodies in lung cells.
摘要翻译：本发明提供了使用BOC / CDO刺猬蛋白拮抗剂抑制刺猬蛋白信号传导的方法，以及治疗和诊断与刺猬蛋白信号传导或过度表达刺猬蛋白有关的疾病，包括癌症，细胞增殖性疾病和血管发生，神经障碍作为受刺猬信号传导影响的其他条件，如毛发生长，神经干细胞分化，软骨形成和成骨，肺表面活性物质生成，在肺细胞中形成层状体。

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