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1. 发明申请

US20130023475A1 C-MET RECEPTOR REGULATION BY ANGIOTENSIN IV (AT4) RECEPTOR LIGANDS 有权
标题翻译： C-MET受体由血管紧张素II（AT4）受体配体调节
公开(公告)号：US20130023475A1
公开(公告)日：2013-01-24
申请号：US13547601
申请日：2012-07-12
申请人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto , Leen H. Kawas
发明人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto , Leen H. Kawas
IPC分类号： A61K38/08 , A61K38/10 , A61P25/16 , A61P25/00
CPC分类号： A61K38/085 , A61K38/1833 , C07K5/06034 , C07K5/06078 , C07K5/06086 , C07K5/06095 , C07K5/06113 , C07K5/0808 , C07K5/0812 , C07K5/0815 , C07K5/0817 , C07K5/0819 , C07K5/101 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K14/705 , G01N33/502 , G01N33/5023 , G01N33/6893 , G01N2800/044
摘要： The cell surface c-Met receptor, through which hepatocyte growth factor (HGF) signals are mediated, has now been identified as the Angiotensin-IV receptor (AT(4)R) in processes that include HGF-regulated cell motility, angiogenesis, cancer metastasis, adipogenesis and others. Disclosed are angiotensin-like factor compositions and methods for using them to diagnose, prevent and/or treat conditions associated with c-Met dysregulation, including cancer, obesity and conditions associated with obesity, and other disorders, for example, by altering hepatocyte growth factor activity or c-Met receptor activity by administering an angiotensin-like factor that specifically binds to a cell surface c-Met receptor. In addition, members of this group of molecules may useful for treating or preventing the development of neurodegenerative diseases like general dementia, Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis and initiating recovery from traumatic brain injury and spinal cord trauma. These peptides and peptidomimetics may be therapeutically useful whenever increased neurotrophic activity would be clinically advantageous.
摘要翻译：肝细胞生长因子（HGF）信号介导的细胞表面c-Met受体已被鉴定为血管紧张素-IV受体（AT（4）R），其包括HGF调节的细胞运动，血管生成，癌症转移，脂肪形成等。公开了血管紧张素样因子组合物和使用它们来诊断，预防和/或治疗与c-Met失调相关的病症的方法，包括癌症，肥胖症和与肥胖相关的病症以及其他病症，例如通过改变肝细胞生长因子活性或c-Met受体活性，通过施用特异性结合细胞表面c-Met受体的血管紧张素样因子。此外，该组分子的成员可用于治疗或预防神经变性疾病如一般性痴呆，阿尔茨海默氏病，帕金森病和肌萎缩性侧索硬化的发展，并且从创伤性脑损伤和脊髓创伤引发恢复。每当增加的神经营养活性在临床上是有利的时候，这些肽和肽模拟物可以是治疗上有用的。

2. 发明授权

US09066901B2 C-Met receptor regulation by angiotensin IV (AT4) receptor ligands 有权
标题翻译：血管紧张素IV（AT4）受体配体的C-Met受体调节
公开(公告)号：US09066901B2
公开(公告)日：2015-06-30
申请号：US13547601
申请日：2012-07-12
申请人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto , Leen H. Kawas
发明人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto , Leen H. Kawas
IPC分类号： A61K38/22 , C07K14/475 , A61K38/00 , A61P3/04 , A61P25/00 , C07K14/47 , A61K38/08 , A61K38/18 , C07K14/705 , C07K5/087 , C07K5/09 , C07K5/093 , C07K5/103 , C07K5/11 , C07K5/113 , G01N33/50 , G01N33/68 , C07K5/107 , C07K5/083 , C07K5/065 , C07K5/072 , C07K5/062 , C07K5/068
CPC分类号： A61K38/085 , A61K38/1833 , C07K5/06034 , C07K5/06078 , C07K5/06086 , C07K5/06095 , C07K5/06113 , C07K5/0808 , C07K5/0812 , C07K5/0815 , C07K5/0817 , C07K5/0819 , C07K5/101 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K14/705 , G01N33/502 , G01N33/5023 , G01N33/6893 , G01N2800/044
摘要： Angiotensin-like factor compositions and methods for using them to diagnose, prevent and/or treat conditions associated with c-Met dysregulation, are provided. The conditions include cancer, obesity, conditions associated with obesity, and neurodegenerative diseases such as general dementia, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, traumatic brain injury and spinal cord trauma.
摘要翻译：提供血管紧张素样因子组合物及其用于诊断，预防和/或治疗与c-Met失调相关的病症的方法。条件包括癌症，肥胖症，与肥胖相关的病症，以及神经变性疾病如一般性痴呆，阿尔茨海默病，帕金森病，肌萎缩性侧索硬化，创伤性脑损伤和脊髓创伤。

3. 发明授权

US07910555B2 C-Met receptor regulation by angiotensin IV (AT4 ) receptor ligands 有权
标题翻译：血管紧张素IV（AT4）受体配体的C-Met受体调节
公开(公告)号：US07910555B2
公开(公告)日：2011-03-22
申请号：US11774517
申请日：2007-07-06
申请人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto
发明人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto
IPC分类号： A61K38/08
CPC分类号： A61K38/085 , A61K38/1833 , C12N9/0008 , C12N9/88 , C12N9/93
摘要： The cell surface c-Met receptor, through which hepatocyte growth factor (HGF) signals are mediated, has now been identified as the Angiotensin-IV receptor (AT(4)R) in processes that include HGF-regulated cell motility, angiogenesis cancer metastasis and others. Disclosed are angiotensin-like factor compositions and methods for using them to diagnose, prevent and/or treat conditions associated with c-Met dysregulation, including altering hepatocyte growth factor activity or c-Met receptor activity by administering an angiotensin-like factor that specifically binds to a cell surface c-Met receptor.
摘要翻译：肝细胞生长因子（HGF）信号介导的细胞表面c-Met受体已被鉴定为包括HGF调节的细胞运动，血管发生癌转移的过程中的血管紧张素-IV受体（AT（4）R）和别的。公开了使用它们来诊断，预防和/或治疗与c-Met失调相关的病症的血管紧张素样因子组合物和方法，包括通过施用特异性结合的血管紧张素样因子来改变肝细胞生长因子活性或c-Met受体活性到细胞表面c-Met受体。

4. 发明授权

US08236761B2 C-Met receptor regulation by angiotensin IV (AT4) receptor ligands 有权
标题翻译：血管紧张素IV（AT4）受体配体的C-Met受体调节
公开(公告)号：US08236761B2
公开(公告)日：2012-08-07
申请号：US11972487
申请日：2008-01-10
申请人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto
发明人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto
IPC分类号： A61K38/18 , A61K38/08 , A61K38/10
CPC分类号： A61K38/085 , A61K38/1833 , C07K5/06034 , C07K5/06078 , C07K5/06086 , C07K5/06095 , C07K5/06113 , C07K5/0808 , C07K5/0812 , C07K5/0815 , C07K5/0817 , C07K5/0819 , C07K5/101 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K14/705 , G01N33/502 , G01N33/5023 , G01N33/6893 , G01N2800/044
摘要： The cell surface c-Met receptor, through which hepatocyte growth factor (HGF) signals are mediated, has now been identified as the Angiotensin-IV receptor (AT(4)R) in processes that include HGF-regulated cell motility, angiogenesis, cancer metastasis, adipogenesis and others. Disclosed are angiotensin-like factor compositions and methods for using them to diagnose, prevent and/or treat conditions associated with c-Met dysregulation, including cancer, obesity and conditions associated with obesity, and other disorders, for example, by altering hepatocyte growth factor activity or c-Met receptor activity by administering an angiotensin-like factor that specifically binds to a cell surface c-Met receptor.
摘要翻译：肝细胞生长因子（HGF）信号介导的细胞表面c-Met受体已被鉴定为血管紧张素-IV受体（AT（4）R），其包括HGF调节的细胞运动，血管生成，癌症转移，脂肪形成等。公开了血管紧张素样因子组合物和使用它们来诊断，预防和/或治疗与c-Met失调相关的病症的方法，包括癌症，肥胖症和与肥胖相关的病症以及其他病症，例如通过改变肝细胞生长因子活性或c-Met受体活性，通过施用特异性结合细胞表面c-Met受体的血管紧张素样因子。

5. 发明申请

US20080293634A1 C-MET RECEPTOR REGULATION BY ANGIOTENSIN IV (AT4) RECEPTOR LIGANDS 有权
标题翻译： C-MET受体由血管紧张素II（AT4）受体配体调节
公开(公告)号：US20080293634A1
公开(公告)日：2008-11-27
申请号：US11972487
申请日：2008-01-10
申请人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto
发明人： Joseph W. Harding , John W. Wright , Patrick D. Elias , Brent J. Yamamoto
IPC分类号： A61K38/00 , C12N5/06 , A61P1/00
CPC分类号： A61K38/085 , A61K38/1833 , C07K5/06034 , C07K5/06078 , C07K5/06086 , C07K5/06095 , C07K5/06113 , C07K5/0808 , C07K5/0812 , C07K5/0815 , C07K5/0817 , C07K5/0819 , C07K5/101 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K14/705 , G01N33/502 , G01N33/5023 , G01N33/6893 , G01N2800/044
摘要： The cell surface c-Met receptor, through which hepatocyte growth factor (HGF) signals are mediated, has now been identified as the Angiotensin-IV receptor (AT(4)R) in processes that include HGF-regulated cell motility, angiogenesis, cancer metastasis, adipogenesis and others. Disclosed are angiotensin-like factor compositions and methods for using them to diagnose, prevent and/or treat conditions associated with c-Met dysregulation, including cancer, obesity and conditions associated with obesity, and other disorders, for example, by altering hepatocyte growth factor activity or c-Met receptor activity by administering an angiotensin-like factor that specifically binds to a cell surface c-Met receptor.
摘要翻译：肝细胞生长因子（HGF）信号介导的细胞表面c-Met受体已被鉴定为血管紧张素-IV受体（AT（4）R），其包括HGF调节的细胞运动，血管生成，癌症转移，脂肪形成等。公开了血管紧张素样因子组合物和使用它们来诊断，预防和/或治疗与c-Met失调相关的病症的方法，包括癌症，肥胖症和与肥胖相关的病症以及其他病症，例如通过改变肝细胞生长因子活性或c-Met受体活性，通过施用特异性结合细胞表面c-Met受体的血管紧张素样因子。

6. 发明申请

US20140088004A1 Hepatocyte Growth Factor Mimics as Therapeutic Agents 有权
标题翻译：肝细胞生长因子模拟作为治疗剂
公开(公告)号：US20140088004A1
公开(公告)日：2014-03-27
申请号：US14009459
申请日：2012-04-02
申请人： Joseph W. Harding , John W. Wright , Caroline C. Benoist , Leen H. Kawas , Gary A. Wayman
发明人： Joseph W. Harding , John W. Wright , Caroline C. Benoist , Leen H. Kawas , Gary A. Wayman
IPC分类号： C07K5/02
CPC分类号： A61K38/06 , A61K38/00 , A61K38/07 , A61K45/06 , C07K5/02 , C07K5/021 , C07K5/0808
摘要： Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia, neurodegenerative disease, diabetes and metabolic syndrome, cancer, and defective wound healing.
摘要翻译：已经产生了作为模拟物和拮抗剂两者的小分子，肽肝细胞生长因子模拟物。已经显示或预测了这些分子具有许多病症的治疗潜力，包括痴呆，神经变性疾病，糖尿病和代谢综合征，癌症和伤口愈合不良。

7. 发明授权

US09150613B2 Hepatocyte growth factor mimics as therapeutic agents 有权
标题翻译：肝细胞生长因子模拟为治疗剂
公开(公告)号：US09150613B2
公开(公告)日：2015-10-06
申请号：US14009459
申请日：2012-04-02
申请人： Joseph W. Harding , John W. Wright , Caroline C. Benoist , Leen H. Kawas , Gary A. Wayman
发明人： Joseph W. Harding , John W. Wright , Caroline C. Benoist , Leen H. Kawas , Gary A. Wayman
IPC分类号： C07K5/02 , A61K38/06 , A61K38/07 , A61K45/06 , C07K5/083 , A61K38/00
CPC分类号： A61K38/06 , A61K38/00 , A61K38/07 , A61K45/06 , C07K5/02 , C07K5/021 , C07K5/0808
摘要： Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia, neurodegenerative disease, diabetes and metabolic syndrome, cancer, and defective wound healing.
摘要翻译：已经产生了作为模拟物和拮抗剂两者的小分子，肽肝细胞生长因子模拟物。已经显示或预测了这些分子具有许多病症的治疗潜力，包括痴呆，神经变性疾病，糖尿病和代谢综合征，癌症和伤口愈合不良。

8. 发明申请

US20170049843A1 Hepatocyte Growth Factor Mimics as Therapeutic Agents 审中-公开
标题翻译：肝细胞生长因子模拟作为治疗剂
公开(公告)号：US20170049843A1
公开(公告)日：2017-02-23
申请号：US14821184
申请日：2015-08-07
申请人： Joseph W. Harding , John W. Wright , Caroline C. Benoist , Leen H. Kawas , Gary A. Wayman
发明人： Joseph W. Harding , John W. Wright , Caroline C. Benoist , Leen H. Kawas , Gary A. Wayman
IPC分类号： A61K38/06 , A61K45/06 , C07K5/083
CPC分类号： A61K38/06 , A61K38/00 , A61K38/07 , A61K45/06 , C07K5/02 , C07K5/021 , C07K5/0808
摘要： Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia, neurodegenerative disease, diabetes and metabolic syndrome, cancer, and defective wound healing.
摘要翻译：已经产生了作为模拟物和拮抗剂两者的小分子，肽肝细胞生长因子模拟物。已经显示或预测了这些分子具有许多病症的治疗潜力，包括痴呆，神经变性疾病，糖尿病和代谢综合征，癌症和伤口愈合不良。

9. 发明授权

US5854388A Angiotensin IV peptides and receptor 失效
标题翻译：血管紧张素IV肽和受体
公开(公告)号：US5854388A
公开(公告)日：1998-12-29
申请号：US360784
申请日：1994-12-22
申请人： Joseph W. Harding , John W. Wright
发明人： Joseph W. Harding , John W. Wright
IPC分类号： A61K38/00 , C07K5/103 , C07K7/14 , C07K14/72 , A61K38/04 , A61K38/06 , C07K5/00 , C07K16/00
CPC分类号： C07K14/72 , C07K5/101 , C07K7/14 , A61K38/00
摘要： A unique and novel angiotensin AT4 receptor and AIV ligand system for binding a small N-terminal hexapeptide fragment of Angiotensin II (referred to as AIV, with amino acid sequence Val.sub.1 -Tyr.sub.2 -Ile.sub.3 -His.sub.4 -Pro.sub.5 -Phe.sub.6 ; SEQ. ID. NO. 1) is disclosed. AIV ligand binds saturably, reversibly, specifically, and with high affinity to membrane AT4 receptors in a variety of tissues, including heart, lung, kidney, aorta, brain, liver, and uterus, from many animal species. The AT4 receptor is pharmacologically distinct from classic angiotensin receptors (AT1 or AT2). The system employs AIV or C-terminally truncated or extended AIV-like peptides (e.g., VYIHPFX; SEQ. ID. NO. 8) as the signaling agent, and the AT4 plasma membrane receptor as the detection mechanism. The angiotensin AT4 receptor and receptor fragments (including the receptor binding site domain) are capable of binding a VYIHPF (SEQ. ID. NO. 1) angiotensin AIV N-terminal peptide but not an angiotensin AII or AIII N-terminal peptide, i.e., DRVYIHPF (SEQ. ID. NO. 2) or RVYIHPF (SEQ. ID. NO. 3), respectively. Also disclosed are processes for isolating angiotensin AT4 receptor and AIV angioteninase, identifying angiotensin AIV agonists and antagonists, and constructing diagnostic assays to specifically measure AIV and AI-specific angiotensinase in biological fluids.
摘要翻译： PCT No.PCT / US93 / 06038 Sec。 371日期1994年12月22日第 102（e）日期1994年12月22日PCT提交1993年6月24日PCT公布。出版物WO94 / 日期1994年1月6日一种用于结合血管紧张素II的小N末端六肽片段（称为AIV，氨基酸序列Val1-Tyr2-Ile3-His4-Pro5-Phe6）的独特且新颖的血管紧张素AT4受体和AIV配体系统; SEQ ID NO：1）。 AIV配体可饱和地，可逆地，具体地以高亲和力结合，从许多动物物种的多种组织，包括心脏，肺，肾，主动脉，脑，肝和子宫中的膜AT4受体结合。 AT4受体在药理上与经典的血管紧张素受体（AT1或AT2）不同。该系统使用AIV或C末端截短或延伸的AIV样肽（例如VYIHPFX; SEQ.ID.NO.8）作为信号传导剂，AT4质膜受体作为检测机制。血管紧张素AT4受体和受体片段（包括受体结合位点结构域）能够结合VYIHPF（SEQ.ID.NO.1）血管紧张素AIV N-末端肽而不是血管紧张素AII或AIII N-末端肽，即， DRVYIHPF（SEQ ID NO：2）或RVYIHPF（SEQ ID NO：3）。还公开了用于分离血管紧张素AT4受体和AIV血管紧张素酶，鉴定血管紧张素AIV激动剂和拮抗剂的方法，以及构建用于特异性测量生物流体中的AIV和AI特异性血管紧张素酶的诊断测定法。

10. 发明申请

US20080194490A1 AT4 RECEPTOR LIGANDS AS ANGIOGENIC, ANTI-ANGIOGENIC, AND ANTI-TUMOR AGENTS 审中-公开
标题翻译： AT4受体配体作为抗原性，抗原性和抗肿瘤剂
公开(公告)号：US20080194490A1
公开(公告)日：2008-08-14
申请号：US11929205
申请日：2007-10-30
申请人： Joseph W. Harding , John W. Wright
发明人： Joseph W. Harding , John W. Wright
IPC分类号： A61K38/08 , C07K7/06 , A61P35/00
CPC分类号： A61K38/06 , A61K38/05 , A61K38/07 , A61K38/08
摘要： AT4 receptor agonists are potent activators of angiogenesis and can be used to treat diseases that are characterized by vascular insufficiency. AT4 receptor antagonists, which are potent inhibitors of angiogenesis, and can be used as anti-angiogenic agents for the treatment of cancer, diabetic retinopathy, rheumatoid arthritis, psoriasis, atherosclerotic plaque formation, and any disease process that is characterized by excessive, undesired or inappropriate angiogenesis or proliferation of endothelial cells.
摘要翻译：受体激动剂是血管发生的有效激活剂，可用于治疗以血管功能不全为特征的疾病。 AT 4受体拮抗剂，其是血管生成的有效抑制剂，并且可以用作抗血管生成剂用于治疗癌症，糖尿病性视网膜病变，类风湿性关节炎，牛皮癣，动脉粥样硬化斑块形成和任何疾病过程其特征在于内皮细胞的过度，不期望或不适当的血管生成或增殖。

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