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1. 发明申请

WO1997007214A1 FUNCTIONAL ROLE OF ADRENOMEDULLIN (AM) AND THE GENE-RELATED PRODUCT (PAMP) IN HUMAN PATHOLOGY AND PHYSIOLOGY 审中-公开
标题翻译： ADRENOMEDULLIN（AM）和基因相关产品（PAMP）在人类病理学和生理学中的功能作用
公开(公告)号：WO1997007214A1
公开(公告)日：1997-02-27
申请号：PCT/US1996013286
申请日：1996-08-16
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , CUTTITTA, Frank , MARTINEZ, Alfredo , MILLER, Mae, Jean , UNSWORTH, Edward, J. , HOOK, William , WALSH, Thomas , GRAY, Karen , MACRI, Charles
发明人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
IPC分类号： C12N15/16
CPC分类号： C07K16/26 , A61K38/00 , A61K39/00 , A61K2039/505 , A61K2039/51 , C07K14/575 , C07K2317/34 , C07K2317/73
摘要： The methods of the present invention demonstrate that adrenomedullin (AM) is expressed in human cancer cell lines of diverse origin and functions as a universal autocrine growth factor driving neoplastic proliferation. The present invention provides for AM peptides and AM antibodies useful in therapeutic, pharmacologic and physiologic compositions. The present invention additionally provides for methods of diagnosis, treatment and prevention of disease utilizing compositions comprising the AM peptides and antibodies of the present invention. The methods of the present invention also provide for experimental models for use in identifying the role of AM in pancreatic physiology. The methods pertaining to rat isolated islets have shown that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was shown by the methods of the present invention to increase insulin release fivefold, an effect that was reversed by the addition of synthetic AM.
摘要翻译：本发明的方法证明，肾上腺髓质素（AM）在不同来源的人类癌细胞系中表达，并且作为驱动肿瘤增殖的通用自分泌生长因子起作用。本发明提供可用于治疗，药理和生理组合物的AM肽和AM抗体。本发明另外提供了使用包含本发明的AM肽和抗体的组合物来诊断，治疗和预防疾病的方法。本发明的方法还提供了用于鉴定AM在胰腺生理学中的作用的实验模型。与大鼠分离的胰岛相关的方法已经表明AM以剂量依赖的方式抑制胰岛素分泌。通过本发明的方法显示了中和AM生物活性的单克隆抗体MoAb-G6，以增加胰岛素释放的五倍，这是通过加入合成AM而逆转的作用。

2. 发明申请

WO2011014825A2 ANTIANGIOGENIC SMALL MOLECULES AND METHODS OF USE 审中-公开
标题翻译：抗血管生成小分子及其使用方法
公开(公告)号：WO2011014825A2
公开(公告)日：2011-02-03
申请号：PCT/US2010/043998
申请日：2010-07-30
申请人： THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , ZUDAIRE, Enrique , APARICIO, Marta , CUTTITTA, Frank
发明人： ZUDAIRE, Enrique , APARICIO, Marta , CUTTITTA, Frank
IPC分类号： A61K31/343 , A61K31/435 , A61K31/519 , A61P35/00 , A61P19/02 , A61P17/06
CPC分类号： A61K38/12 , A61K31/10 , A61K31/135 , A61K31/285 , A61K31/4015 , A61K31/445 , A61K31/5365 , A61K31/555 , A61K31/63 , A61K45/06 , A61K2300/00
摘要： Methods of inhibiting undesired angiogenesis are provided, which methods include administering to a subject a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt thereof.
摘要翻译：提供了抑制不希望的血管发生的方法，所述方法包括向受试者施用治疗有效量的至少一种本文所述的化合物或其药学上可接受的盐。

3. 发明申请

WO2005026741B1 NON-PEPTIDE AGONISTS AND ANTAGONISTS OF ADRENOMEDULLIN AND GASTRIN RELEASING PEPTIDE 审中-公开
标题翻译：肾上腺素和胃泌素释放肽的非肽类激动剂和拮抗剂
公开(公告)号：WO2005026741B1
公开(公告)日：2005-10-13
申请号：PCT/US2004029293
申请日：2004-09-08
申请人： US GOV HEALTH & HUMAN SERV , CUTTITTA FRANK , MARTINEZ ALFREDO
发明人： CUTTITTA FRANK , MARTINEZ ALFREDO
IPC分类号： A61K31/194 , A61K31/4196 , A61K31/445 , A61K31/4453 , A61K31/45 , A61K38/22 , A61P3/10 , A61P9/02 , A61P9/08 , A61P9/10 , A61P35/00 , G01N33/74
CPC分类号： A61K47/48246 , A61K31/192 , A61K31/194 , A61K31/197 , A61K31/4196 , A61K31/433 , A61K31/439 , A61K31/44 , A61K31/445 , A61K31/4453 , A61K31/45 , A61K31/52 , A61K38/22 , G01N33/68 , G01N33/74 , G01N2333/5758 , G01N2500/04 , A61K2300/00
摘要： This invention relates, e.g., to methods for inhibiting or stimulating an activity of an adrenomedullin (AM) or gastrin releasing peptide (GRP) peptide hormone, comprising contacting the peptide with a small molecule, non-peptide, modulatory agent whicg binds to the hormone moiety, rather than to the the hormone receptors. Complexes of these modulatory agents with other components, such as the peptides or blocking antibodies specific for the peptides, are also described, as are pharmaceutical compositions comprising the modulatory agents, and methods for using the modulatory agents to diagnose or treat patients.
摘要翻译：本发明涉及例如抑制或刺激肾上腺髓质素（AM）或胃泌素释放肽（GRP）肽激素的活性的方法，所述方法包括使所述肽与小分子非肽调节剂接触，所述调节剂与激素结合部分，而不是激素受体。还描述了这些调节剂与其他组分的络合物，例如肽特异性的肽或封闭抗体，以及包含调节剂的药物组合物，以及使用调节剂诊断或治疗患者的方法。

4. 发明申请

WO2001018550A3 DETERMINATION OF ADRENOMEDULLIN-BINDING PROTEINS 审中-公开
公开(公告)号：WO2001018550A3
公开(公告)日：2001-03-15
申请号：PCT/US2000/024722
申请日：2000-09-08
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , CUTTITTA, Frank , ELSASSER, Ted, H. , MARTINEZ, Alfredo , PIO, Ruben
发明人： CUTTITTA, Frank , ELSASSER, Ted, H. , MARTINEZ, Alfredo , PIO, Ruben
IPC分类号： G01N33/74
摘要： The present invention provides methods for the isolation, identification, and purification of adrenomedullin (AM)-binding proteins. Also, provided are methods for utilizing the purified AM-binding proteins, or functional portions thereof, to diagnose, treat, and monitor AM-related diseases, for example, diseases or disorders associated with abnormally elevated AM levels. In addition, the present invention provides a newly identified complex between AM and a specific AM-binding protein 1 (AMBP-1); which has been isolated and identified herein as factor H (fH). The invention also provides AM/AMBP complexes, particularly AM/fH complexes, and antibodies specifically reactive with these complexes. Further provided are methods for identifying and purifying complexes of AM and an AM binding protein using anti-AM/fH antibodies, and methods for treating conditions such as cancer or diabetes utilizing compositions comprising these antibodies. The present invention additionally provides methods for identifying antagonists agents that inhibit the function of AM, factor H, or the AM/factor H complex. The invention also provides methods for treating conditions such as cancer or diabetes using these antagonist agents.

5. 发明申请

WO2011014825A3 ANTIANGIOGENIC SMALL MOLECULES AND METHODS OF USE 审中-公开
标题翻译：抗生素小分子和使用方法
公开(公告)号：WO2011014825A3
公开(公告)日：2011-06-16
申请号：PCT/US2010043998
申请日：2010-07-30
申请人： US HEALTH , ZUDAIRE ENRIQUE , APARICIO MARTA , CUTTITTA FRANK
发明人： ZUDAIRE ENRIQUE , APARICIO MARTA , CUTTITTA FRANK
IPC分类号： A61K31/343 , A61K31/435 , A61K31/519 , A61P17/06 , A61P19/02 , A61P35/00
CPC分类号： A61K38/12 , A61K31/10 , A61K31/135 , A61K31/285 , A61K31/4015 , A61K31/445 , A61K31/5365 , A61K31/555 , A61K31/63 , A61K45/06 , A61K2300/00
摘要： Methods of inhibiting undesired angiogenesis are provided, which methods include administering to a subject a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt thereof.
摘要翻译：提供了抑制不希望的血管生成的方法，所述方法包括向受试者施用治疗有效量的至少一种本文所述的化合物或其药学上可接受的盐。

6. 发明申请

WO2004043383A3 A NEW TARGET FOR ANGIOGENESIS AND ANTI-ANGIOGENESIS THERAPY 审中-公开
标题翻译：一种新的血液发生和抗血栓形成治疗的目标
公开(公告)号：WO2004043383A3
公开(公告)日：2006-02-23
申请号：PCT/US0335633
申请日：2003-11-07
申请人： US GOV HEALTH & HUMAN SERV , CUTTITTA FRANK , MARTINEZ ALFREDO , STETLER-STEVENSON WILLIAM G
发明人： CUTTITTA FRANK , MARTINEZ ALFREDO , STETLER-STEVENSON WILLIAM G
IPC分类号： A61K20060101 , A61K6/00 , A61K38/10 , A61K38/22 , A61P9/00 , C07K7/08 , C07K14/575 , C12N15/00 , G01N33/53 , G01N33/74
CPC分类号： G01N33/74 , A61K38/00 , A61K38/1825 , A61K38/1866 , C07K14/575 , G01N2333/515 , G01N2500/00 , G01N2500/02 , A61K2300/00
摘要： The present disclosure concerns the use of peptides and compositions, such as pharmaceutical compositions, to influence angiogenesis. Particular methods are useful for promoting angiogenesis, while others are particularly useful for inhibiting angiogenesis.

7. 发明申请

WO2004043383A8 A NEW TARGET FOR ANGIOGENESIS AND ANTI-ANGIOGENESIS THERAPY 审中-公开
标题翻译：一种新的血液发生和抗血栓形成治疗的目标
公开(公告)号：WO2004043383A8
公开(公告)日：2005-06-09
申请号：PCT/US0335633
申请日：2003-11-07
申请人： US GOV HEALTH & HUMAN SERV , CUTTITTA FRANK , MARTINEZ ALFREDO , STETLER-STEVENSON WILLIAM G
发明人： CUTTITTA FRANK , MARTINEZ ALFREDO , STETLER-STEVENSON WILLIAM G
IPC分类号： A61K20060101 , A61K6/00 , A61K38/10 , A61K38/22 , A61P9/00 , C07K7/08 , C07K14/575 , C12N15/00 , G01N33/53 , G01N33/74 , C07K7/00 , A61K38/08 , G01N33/567
CPC分类号： G01N33/74 , A61K38/00 , A61K38/1825 , A61K38/1866 , C07K14/575 , G01N2333/515 , G01N2500/00 , G01N2500/02 , A61K2300/00
摘要： The present disclosure concerns the use of peptides and compositions, such as pharmaceutical compositions, to influence angiogenesis. Particular methods are useful for promoting angiogenesis, while others are particularly useful for inhibiting angiogenesis.
摘要翻译：本公开涉及使用肽和组合物，例如药物组合物来影响血管发生。特别的方法可用于促进血管生成，而其它方法对于抑制血管发生特别有用。

8. 发明申请

WO0118550A9 DETERMINATION OF ADRENOMEDULLIN-BINDING PROTEINS 审中-公开
标题翻译： ADRENOMEDULLIN结合蛋白的测定
公开(公告)号：WO0118550A9
公开(公告)日：2002-09-26
申请号：PCT/US0024722
申请日：2000-09-08
申请人： US GOV HEALTH & HUMAN SERV , CUTTITTA FRANK , ELSASSER TED H , MARTINEZ ALFREDO , PIO RUBEN
发明人： CUTTITTA FRANK , ELSASSER TED H , MARTINEZ ALFREDO , PIO RUBEN
IPC分类号： A61K38/17 , C07K16/18 , G01N33/74 , A61K38/00 , C07K16/00
CPC分类号： C07K16/18 , A61K38/1709 , A61K2039/505 , G01N33/74 , G01N2500/00
摘要： The present invention provides methods for the isolation, identification, and purification of adrenomedullin (AM)-binding proteins. Also, provided are methods for utilizing the purified AM-binding proteins, or functional portions thereof, to diagnose, treat, and monitor AM-related diseases, for example, diseases or disorders associated with abnormally elevated AM levels. In addition, the present invention provides a newly identified complex between AM and a specific AM-binding protein 1 (AMBP-1); which has been isolated and identified herein as factor H (fH). The invention also provides AM/AMBP complexes, particularly AM/fH complexes, and antibodies specifically reactive with these complexes. Further provided are methods for identifying and purifying complexes of AM and an AM binding protein using anti-AM/fH antibodies, and methods for treating conditions such as cancer or diabetes utilizing compositions comprising these antibodies. The present invention additionally provides methods for identifying antagonists agents that inhibit the function of AM, factor H, or the AM/factor H complex. The invention also provides methods for treating conditions such as cancer or diabetes using these antagonist agents.
摘要翻译：本发明提供了分离，鉴定和纯化肾上腺髓质素（AM）结合蛋白的方法。此外，提供了利用纯化的AM结合蛋白或其功能部分来诊断，治疗和监测AM相关疾病的方法，例如与异常升高的AM水平相关的疾病或病症。此外，本发明提供了AM和特异性AM结合蛋白1（AMBP-1）之间新鉴定的复合物; 其在本文中被分离和鉴定为因子H（fH）。本发明还提供AM / AMBP复合物，特别是AM / fH复合物和与这些复合物特异性反应的抗体。进一步提供了使用抗AM / fH抗体鉴定和纯化AM和AM结合蛋白的复合物的方法，以及使用包含这些抗体的组合物治疗诸如癌症或糖尿病的病症的方法。本发明另外提供用于鉴定抑制AM，因子H或AM /因子H复合物的功能的拮抗剂的方法。本发明还提供了使用这些拮抗剂治疗诸如癌症或糖尿病的病症的方法。

9. 发明申请

WO2005026741A3 NON-PEPTIDE AGONISTS AND ANTAGONISTS OF ADRENOMEDULLIN AND GASTRIN RELEASING PEPTIDE 审中-公开
标题翻译：非特异性激素和阿霉素和胃泌素释放肽的拮抗剂
公开(公告)号：WO2005026741A3
公开(公告)日：2005-08-18
申请号：PCT/US2004029293
申请日：2004-09-08
申请人： US GOV HEALTH & HUMAN SERV , CUTTITTA FRANK , MARTINEZ ALFREDO
发明人： CUTTITTA FRANK , MARTINEZ ALFREDO
IPC分类号： A61K31/194 , A61K31/4196 , A61K31/445 , A61K31/4453 , A61K31/45 , A61K38/22 , A61P3/10 , A61P9/02 , A61P9/08 , A61P9/10 , A61P35/00 , G01N33/74
CPC分类号： A61K47/48246 , A61K31/192 , A61K31/194 , A61K31/197 , A61K31/4196 , A61K31/433 , A61K31/439 , A61K31/44 , A61K31/445 , A61K31/4453 , A61K31/45 , A61K31/52 , A61K38/22 , G01N33/68 , G01N33/74 , G01N2333/5758 , G01N2500/04 , A61K2300/00
摘要： This invention relates, e.g., to methods for inhibiting or stimulating an activity of an adrenomedullin (AM) or gastrin releasing peptide (GRP) peptide hormone, comprising contacting the peptide with a small molecule, non-peptide, modulatory agent whicg binds to the hormone moiety, rather than to the the hormone receptors. Complexes of these modulatory agents with other components, such as the peptides or blocking antibodies specific for the peptides, are also described, as are pharmaceutical compositions comprising the modulatory agents, and methods for using the modulatory agents to diagnose or treat patients.
摘要翻译：本发明涉及例如用于抑制或刺激肾上腺髓质素（AM）或促胃泌素释放肽（GRP）肽激素的活性的方法，包括使肽与小分子接触，非肽，调节剂与激素结合部分，而不是激素受体。还描述了这些调节剂与其它成分的复合物，例如对于肽特异的肽或阻断抗体，以及包含调节剂的药物组合物以及使用调节剂诊断或治疗患者的方法。

10. 发明申请

WO2005026741A2 NON-PEPTIDE AGONISTS AND ANTAGONISTS OF ADRENOMEDULLIN AND GASTRIC RELEASING PEPTIDE 审中-公开
标题翻译：非特异性促胰岛素和胃泌素释放肽的非肽激素和拮抗剂
公开(公告)号：WO2005026741A2
公开(公告)日：2005-03-24
申请号：PCT/US2004/029293
申请日：2004-09-08
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, ASrepresented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , CUTTITTA, Frank , MARTINEZ, Alfredo
发明人： CUTTITTA, Frank , MARTINEZ, Alfredo
IPC分类号： G01N33/74
CPC分类号： A61K47/48246 , A61K31/192 , A61K31/194 , A61K31/197 , A61K31/4196 , A61K31/433 , A61K31/439 , A61K31/44 , A61K31/445 , A61K31/4453 , A61K31/45 , A61K31/52 , A61K38/22 , G01N33/68 , G01N33/74 , G01N2333/5758 , G01N2500/04 , A61K2300/00
摘要： This invention relates, e.g., to methods for inhibiting or stimulating an activity of an adrenomedullin (AM) or gastrin releasing peptide (GRP) peptide hormone, comprising contacting the peptide with a small molecule, non-peptide, modulatory agent of the invention. Complexes of these modulatory agents with other components, such as the peptides or blocking antibodies specific for the peptides, are also described, as are pharmaceutical compositions comprising the modulatory agents, and methods for using the modulatory agents to diagnose or treat patients.
摘要翻译：本发明涉及例如用于抑制或刺激肾上腺髓质素（AM）或胃泌素释放肽（GRP）肽激素的活性的方法，包括使肽与本发明的小分子非肽调节剂接触。还描述了这些调节剂与其它成分的复合物，例如对于肽特异的肽或阻断抗体，以及包含调节剂的药物组合物以及使用调节剂诊断或治疗患者的方法。

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