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1. 发明授权

US07473770B2 Cynomolgus monkey dickkopf-4, nucleotides encoding same, and uses thereof 失效
标题翻译：食蟹猴dickkopf-4，编码相同的核苷酸及其用途
公开(公告)号：US07473770B2
公开(公告)日：2009-01-06
申请号：US10579596
申请日：2004-11-12
申请人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantschnig
发明人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantschnig
IPC分类号： C07H21/04 , C12P21/06
CPC分类号： C07K14/47 , G01N2333/4703 , G01N2800/108
摘要： The cynomolgus monkey Dickkopf-4 (cDkk-4) protein, isolated nucleic acid molecules which encode the cDkk-4 protein, and recombinant vectors and hosts comprising DNA encoding the cDkk-4 protein are disclosed. Also disclosed are methods for identifying analytes which interfere with the interaction between the cDkk-4 protein and a homologous or heterologous Dkk receptor and analytes which interfere with the interaction and stimulate bone formation. Analytes identified using the methods are useful for treating osteoporosis and other bone loss disorders.
摘要翻译：公开了食蟹猴Dickkopf-4（cDkk-4）蛋白，编码cDkk-4蛋白的分离的核酸分子以及包含编码cDkk-4蛋白的DNA的重组载体和宿主。还公开了用于鉴定干扰cDkk-4蛋白与同源或异源Dkk受体之间的相互作用以及干扰相互作用并刺激骨形成的分析物的分析物的方法。使用该方法鉴定的分析物可用于治疗骨质疏松症和其他骨丢失障碍。

2. 发明申请

US20070111253A1 Rhesus monkey dickkopf-1, nucleotides encoding same, and uses thereof 失效
标题翻译：恒河猴dickkopf-1，编码相同的核苷酸及其用途
公开(公告)号：US20070111253A1
公开(公告)日：2007-05-17
申请号：US10579605
申请日：2004-11-12
申请人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantsching
发明人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantsching
IPC分类号： G01N33/53 , C07H21/04 , C12P21/06 , C12N5/06 , C07K14/705
CPC分类号： C07K14/47 , C07K14/705 , G01N2333/4715 , G01N2500/10 , G01N2800/108
摘要： The present invention provides rhesus monkey dickkopf-1 (rhDkk-1) and nucleotide sequences encoding it. Also provided herein are recombinant vectors, and recombinant hosts comprising rhDkk-1-encoding nucleotide sequences. Isolated rhDkk-1 can be used to screen and identify novel osteoanabolic compounds that stimulate bone formation for the treatment of osteoporosis or other disorders characterized by insufficient bone mass.
摘要翻译：本发明提供恒河猴dickkopf-1（rhDkk-1）和编码它的核苷酸序列。本文还提供了重组载体和包含编码rhDkk-1的核苷酸序列的重组宿主。分离的rhDkk-1可用于筛选和鉴定刺激骨形成的新型骨代谢化合物，用于治疗骨质疏松症或以骨量不足为特征的其他病症。

3. 发明授权

US06645974B2 Androgen receptor modulators and methods for use thereof 失效
标题翻译：雄激素受体调节剂及其使用方法
公开(公告)号：US06645974B2
公开(公告)日：2003-11-11
申请号：US10205634
申请日：2002-07-25
申请人： John H. Hutchinson , Michael J. Breslin , Gideon A. Rodan , Soumya P. Sahoo , Mark E. Duggan , Shun-Ichi Harada , Azriel Schmidt , Wasyl Halczenko , Dwight A. Towler
发明人： John H. Hutchinson , Michael J. Breslin , Gideon A. Rodan , Soumya P. Sahoo , Mark E. Duggan , Shun-Ichi Harada , Azriel Schmidt , Wasyl Halczenko , Dwight A. Towler
IPC分类号： A61K3158
CPC分类号： C07J73/005 , A61K31/435 , A61K31/473 , A61K31/58 , C07D221/18 , C07D401/12 , C07D405/12 , C07D409/12
摘要： Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and in combination with other active agents.
摘要翻译：公开了本文定义的结构式（I）的化合物可用于在需要这种调节的患者中以组织选择性方式调节雄激素受体的方法，以及在患者中激动雄激素受体的方法，特别是其中雄性受体在男性患者的前列腺或女性患者的子宫中被拮抗并在骨和/或肌肉组织中激动的方法。这些化合物可用于治疗由雄激素缺乏引起的或可由雄激素施用而改善的病症，包括：骨质疏松症，牙周病，骨折，骨重建手术后的骨损伤，肌肉减少症，虚弱，衰老皮肤，男性性腺机能减退妇女的绝经症状，动脉粥样硬化，高胆固醇血症，高脂血症，再生障碍性贫血和其他造血障碍，胰腺癌，肾癌，关节炎和关节修复，单独或与其他活性剂组合。此外，这些化合物可单独用作药物组合物成分并与其它活性剂组合使用。

4. 发明申请

US20070087384A1 CYNOMOLGUS MONKEY DICKKOPE-4, NUCLEOTIDES ENCODING SAME, AND USES THEREOF 失效
标题翻译： CYNOMOLGUS MONKEY DICKKOPE-4，编码它们的核苷酸及其用途
公开(公告)号：US20070087384A1
公开(公告)日：2007-04-19
申请号：US10579596
申请日：2004-11-12
申请人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantschnig
发明人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantschnig
IPC分类号： G01N33/53 , C07H21/04 , C12P21/06 , C07K14/705
CPC分类号： C07K14/47 , G01N2333/4703 , G01N2800/108
摘要： The cynomolgus monkey Dickkopf-4 (cDkk-4) protein, isolated nucleic acid molecules which encode the cDkk-4 protein, and recombinant vectors and hosts comprising DNA encoding the cDkk-4 protein are disclosed. Also disclosed are methods for identifying analytes which interfere with the interaction between the cDkk-4 protein and a homologous or heterologous Dkk receptor and analytes which interfere with the interaction and stimulate bone formation. Analytes identified using the methods are useful for treating osteoporosis and other bone loss disorders.
摘要翻译：公开了食蟹猴Dickkopf-4（cDkk-4）蛋白，编码cDkk-4蛋白的分离的核酸分子以及包含编码cDkk-4蛋白的DNA的重组载体和宿主。还公开了用于鉴定干扰cDkk-4蛋白与同源或异源Dkk受体之间的相互作用以及干扰相互作用并刺激骨形成的分析物的分析物的方法。使用该方法鉴定的分析物可用于治疗骨质疏松症和其他骨丢失障碍。

5. 发明授权

US06376477B2 Combination of an agent that binds to the androgen receptor and a bisphosphonic acid in the prevention and/or treatment of diseases involving calcium or phosphate metabolism 失效
标题翻译：在预防和/或治疗涉及钙或磷酸盐代谢的疾病中结合雄激素受体的药剂和双膦酸的组合
公开(公告)号：US06376477B2
公开(公告)日：2002-04-23
申请号：US09740338
申请日：2000-12-19
申请人： Azriel Schmidt , Shun-Ichi Harada , Gideon Rodan
发明人： Azriel Schmidt , Shun-Ichi Harada , Gideon Rodan
IPC分类号： A61K3166
CPC分类号： A61K31/66 , A61K2300/00
摘要： The inhibition of natural bone formation experienced in the prophylaxis and/or treatment of bone resorption disease with a bisphosphonic acid or a pharmaceutically acceptable salt thereof is overcome by the concommitant administration of an agent that binds to the androgen receptor.
摘要翻译：用双膦酸或其药学上可接受的盐预防和/或治疗骨吸收疾病所经历的天然骨形成的抑制通过与雄激素受体结合的试剂的同时施用来克服。

6. 发明授权

US6090544A Methods and compositions for identifying morphogen analogs 失效
标题翻译：用于鉴定形态发生物类似物的方法和组合物
公开(公告)号：US6090544A
公开(公告)日：2000-07-18
申请号：US764522
申请日：1996-12-12
申请人： Shun-ichi Harada , Gideon A. Rodan , Kuber T. Sampath
发明人： Shun-ichi Harada , Gideon A. Rodan , Kuber T. Sampath
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/16 , A61P9/00 , A61P9/10 , A61P19/00 , A61P19/08 , A61P25/28 , A61P29/00 , A61P43/00 , C07K14/51 , C12N15/12 , C12Q1/68 , C12N5/10 , C12N15/11
CPC分类号： C07K14/51 , A61K38/00
摘要： Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要翻译：本文公开了用于鉴定形态发生类似物的方法和组合物。优选的方法和组合物涉及小鼠X型胶原启动子活性的形态发生上调由MEF-2样序列介导并需要相邻的AP-1序列的发现。某些方法依赖于使用测试细胞，其包括定义与报告基因可操作地相关的形态发生反应性转录激活元件的DNA。其他方法依赖于使用DNA来测量形态发生诱导型DNA结合。在某些优选的实施方案中，所述方法和DNA涉及成骨蛋白1（OP-1）响应转录激活元件。介导与OP-1反应性转录激活元件的相互作用和/或激活的物质在本文中被认为可能用于再现诸如OP-1的形态发生体的作用。

7. 发明申请

US20080003675A1 Methods and compositions for identifying morphogen analogs 审中-公开
标题翻译：用于鉴定形态发生物类似物的方法和组合物
公开(公告)号：US20080003675A1
公开(公告)日：2008-01-03
申请号：US11801900
申请日：2007-05-11
申请人： Shun-ichi Harada , Gideon Rodan , Kuber Sampath
发明人： Shun-ichi Harada , Gideon Rodan , Kuber Sampath
IPC分类号： C12N5/10 , C07H21/04
CPC分类号： C07K14/4705 , A61K38/00 , C07K14/51
摘要： Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要翻译：本文公开了用于鉴定形态发生类似物的方法和组合物。优选的方法和组合物涉及小鼠X型胶原启动子活性的形态发生上调由MEF-2样序列介导并需要相邻的AP-1序列的发现。某些方法依赖于使用测试细胞，其包括定义与报告基因可操作地相关的形态发生反应性转录激活元件的DNA。其他方法依赖于使用DNA来测量形态发生诱导型DNA结合。在某些优选的实施方案中，所述方法和DNA涉及成骨蛋白1（OP-1）响应转录激活元件。介导与OP-1反应性转录激活元件的相互作用和/或激活的物质在本文中被认为可能用于再现诸如OP-1的形态发生体的作用。

8. 发明授权

US06586457B2 Methods for inhibiting bone resorption 失效
公开(公告)号：US06586457B2
公开(公告)日：2003-07-01
申请号：US09817424
申请日：2001-03-26
申请人： Shun-Ichi Harada , Mohamed MacHwate , Gideon A. Rodan , Marc Labelle , Kathleen Metters , Robert N. Young
发明人： Shun-Ichi Harada , Mohamed MacHwate , Gideon A. Rodan , Marc Labelle , Kathleen Metters , Robert N. Young
IPC分类号： A61K3141
CPC分类号： G01N33/88 , A61K31/00 , A61K31/4196 , A61K31/66 , A61K31/663 , A61K45/06 , G01N2500/04 , G01N2500/10 , A61K2300/00
摘要： The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.

9. 发明授权

US5834188A Methods and compositions for identifying morphogen analogs 失效
标题翻译：用于鉴定形态发生物类似物的方法和组合物
公开(公告)号：US5834188A
公开(公告)日：1998-11-10
申请号：US507598
申请日：1995-07-26
申请人： Shun-ichi Harada , Kuber T. Sampath , Gideon A. Rodan
发明人： Shun-ichi Harada , Kuber T. Sampath , Gideon A. Rodan
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/16 , A61P9/00 , A61P9/10 , A61P19/00 , A61P19/08 , A61P25/28 , A61P29/00 , A61P43/00 , C07K14/51 , C12Q1/68 , C12N5/00 , C12Q1/02
CPC分类号： C07K14/51 , A61K38/00
摘要： Disclosed herein are methods and compositions for identifying morphogen analogs. Preferred methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. In certain embodiments, the methods involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要翻译：本文公开了用于鉴定形态发生类似物的方法和组合物。优选的方法在于使用测试细胞，所述测试细胞包含限定与报告基因操作相关的形态发生反应性转录激活元件的DNA。在某些实施方案中，所述方法涉及成骨蛋白1（OP-1）响应转录激活元件。本文认为激活OP-1反应性转录激活元件的物质可能用于再现诸如OP-1的形态发生体的作用。

10. 发明授权

US07622553B2 Rhesus monkey dickkopf-1, nucleotides encoding same, and uses thereof 失效
标题翻译：恒河猴dickkopf-1，编码相同的核苷酸及其用途
公开(公告)号：US07622553B2
公开(公告)日：2009-11-24
申请号：US10579605
申请日：2004-11-12
申请人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantschnig
发明人： Shun-ichi Harada , Viera Kasparcova , Helmut Glantschnig
IPC分类号： C07K14/00 , C07K17/00 , G01N33/53
CPC分类号： C07K14/47 , C07K14/705 , G01N2333/4715 , G01N2500/10 , G01N2800/108
摘要： The present invention provides rhesus monkey dickkopf-1 (rhDkk-1) and nucleotide sequences encoding it. Also provided herein are recombinant vectors, and recombinant hosts comprising rhDkk-1-encoding nucleotide sequences. Isolated rhDkk-1 can be used to screen and identify novel osteoanabolic compounds that stimulate bone formation for the treatment of osteoporosis or other disorders characterized by insufficient bone mass.
摘要翻译：本发明提供恒河猴dickkopf-1（rhDkk-1）和编码它的核苷酸序列。本文还提供了重组载体和包含编码rhDkk-1的核苷酸序列的重组宿主。分离的rhDkk-1可用于筛选和鉴定刺激骨形成的新型骨代谢化合物，用于治疗骨质疏松症或以骨量不足为特征的其他病症。

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