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1.发明授权Functional role of adrenomedullin (AM) and the gene related product (PAMP) in human pathology and physiology 有权肾上腺髓质素（AM）和基因相关产物（PAMP）在人类病理和生理学中的功能作用公开(公告)号：US07939639B2
公开(公告)日：2011-05-10
申请号：US12569821
申请日：2009-09-29
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395 , A61K39/00 , G01N33/53
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 show that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was show 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。 与大鼠分离的胰岛有关的方法表明，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。
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2.发明授权Determination of AM-binding proteins and the association of adrenomedullin (AM) therewith 有权AM结合蛋白的测定和肾上腺髓质素（AM）与其结合公开(公告)号：US07659081B2
公开(公告)日：2010-02-09
申请号：US12236418
申请日：2008-09-23
申请人： Frank Cuttitta , Ted H. Elsasser , Alfredo Martinez , Rubén Pio
发明人： Frank Cuttitta , Ted H. Elsasser , Alfredo Martinez , Rubén Pio
IPC分类号： G01N33/53
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 this 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。
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3.发明授权Functional role of adrenomedullin (AM) and the gene-related product (PAMP) in human pathology and physiology 失效肾上腺髓质素（AM）和基因相关产物（PAMP）在人类病理和生理学中的功能作用公开(公告)号：US07622272B2
公开(公告)日：2009-11-24
申请号：US11517599
申请日：2006-09-05
申请人： Frank Cuttitta , Alfredo Martinez
发明人： Frank Cuttitta , Alfredo Martinez
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 show that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was show 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。 与大鼠分离的胰岛有关的方法表明，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。
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公开(公告)号：US07462593B2
公开(公告)日：2008-12-09
申请号：US10529116
申请日：2003-11-07
IPC分类号： A61K38/00
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。
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公开(公告)号：US20120129775A1
公开(公告)日：2012-05-24
申请号：US13387969
申请日：2010-07-30
申请人： Enrique Zudaire , Marta Aparicio , Frank Cuttitta
发明人： Enrique Zudaire , Marta Aparicio , Frank Cuttitta
IPC分类号： A61K38/12 , A61K31/10 , A61K31/555 , A61P17/06 , A61K31/285 , A61P35/00 , A61P27/02 , A61P19/02 , A61K31/137 , A61K31/5365
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。
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6.发明授权Methods for inhibiting angiogenesis with inhibitors of proadrenomedullin N-terminal 20 peptide (PAMP) 有权用肾上腺髓质素N末端20肽（PAMP）抑制剂抑制血管生成的方法公开(公告)号：US07862815B2
公开(公告)日：2011-01-04
申请号：US12240656
申请日：2008-09-29
IPC分类号： A61K39/395 , A61K38/08 , C07K4/12 , C07K7/06 , C07K16/18
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。
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7.发明申请DETERMINATION OF AM-BINDING PROTEINS AND THE ASSOCIATION OF ADRENOMEDULLIN (AM) THEREWITH 有权AM结合蛋白的测定和ADRENOMEDULLIN（AM）的关联公开(公告)号：US20100098703A1
公开(公告)日：2010-04-22
申请号：US12638747
申请日：2009-12-15
申请人： Frank Cuttitta , Ted H. Elsasser , Alfredo Martinez , Rubén Pío
发明人： Frank Cuttitta , Ted H. Elsasser , Alfredo Martinez , Rubén Pío
IPC分类号： A61K39/395 , C07K14/00 , A61K38/16 , C07K16/00 , A61P43/00 , G01N33/543 , G01N33/53
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 this 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复合物和与该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。
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8.发明申请FUNCTIONAL ROLE OF ADRENOMEDULLIN (AM) AND THE GENE RELATED PRODUCT (PAMP) IN HUMAN PATHOLOGY AND PHYSIOLOGY 有权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：US20100021469A1
公开(公告)日：2010-01-28
申请号：US12569821
申请日：2009-09-29
申请人： Frank Cuttitta , Alfredo Martinez , Mae Jean Miller , Edward J. Unsworth , William A. Hook , Thomas Walsh , Karen Gray , Charles Macri
发明人： Frank Cuttitta , Alfredo Martinez , Mae Jean Miller , Edward J. Unsworth , William A. Hook , Thomas Walsh , Karen Gray , Charles Macri
IPC分类号： A61K39/395 , C07K16/00 , G01N33/53 , A61P7/12 , A61P37/00
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 show that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was show 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。 与大鼠分离的胰岛有关的方法表明，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。
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9.发明申请Non Peptide Agonists and Antagonists of Adrenomedullin and Gastric Releasing Peptide 审中-公开非肽类激动剂和肾上腺髓质素和胃释放肽的拮抗剂公开(公告)号：US20080249115A1
公开(公告)日：2008-10-09
申请号：US10571012
申请日：2004-09-08
申请人： Frank Cuttitta , Alfredo Martinez
发明人： Frank Cuttitta , Alfredo Martinez
IPC分类号： A61K31/52 , C07D403/06 , A61K31/4196 , C07C251/18 , A61K31/4245 , A61K31/122 , C07C39/10 , A61P35/00 , G01N33/68 , A61K31/055 , C07C49/807 , C07D413/06 , A61K31/13 , C07D473/18
CPC分类号： A61K31/52 , A61K31/192 , A61K31/194 , A61K31/197 , A61K31/4196 , A61K31/433 , A61K31/439 , A61K31/44 , A61K31/445 , A61K31/4453 , A61K31/45 , 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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10.发明授权Methods of monitoring angiogenesis and metastasis in three dimensional co-cultures 有权监测三维共培养血管生成和转移的方法公开(公告)号：US08679836B2
公开(公告)日：2014-03-25
申请号：US12802666
申请日：2010-06-10
申请人： Enrique Zudaire , Frank Cuttitta , Changge Fang
发明人： Enrique Zudaire , Frank Cuttitta , Changge Fang
CPC分类号： G01N33/5011 , G01N33/5005 , G01N33/5017 , G01N33/5044
摘要： This disclosure relates to fluorescent cell lines and to the use of such cell lines in monitoring cellular activity, such as angiogenesis. This disclosure further relates to the use of such cell lines in a three-dimensional cell culture to monitor angiogenic and metastatic potential of tumor cells and selecting personalized therapeutics for treatment of cancer.
摘要翻译： 本公开涉及荧光细胞系和这种细胞系用于监测细胞活性如血管生成的用途。 本公开还涉及这样的细胞系在三维细胞培养物中用于监测肿瘤细胞的血管生成和转移潜力并选择用于治疗癌症的个性化治疗剂。
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