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。

公开(公告)号：US07101548B2

公开(公告)日：2006-09-05

申请号：US09931700

申请日：2001-08-16

申请人： Frank Cuttitta ,  Alfredo Martinez ,  Mae Jean Miller ,  Edward J. Unsworth ,  William Hook ,  Thomas Walsh ,  Karen Gray ,  Charles Macri

发明人： Frank Cuttitta ,  Alfredo Martinez ,  Mae Jean Miller ,  Edward J. Unsworth ,  William Hook ,  Thomas Walsh ,  Karen Gray ,  Charles Macri

IPC分类号： A61K39/395

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。

公开(公告)号：US20070004630A1

公开(公告)日：2007-01-04

申请号：US11517599

申请日：2006-09-05

申请人： Frank Cuttitta ,  Alfredo Martinez ,  Mae Miller ,  Edward Unsworth ,  William Hook ,  Thomas Walsh ,  Karen Gray ,  Charles Macri

发明人： Frank Cuttitta ,  Alfredo Martinez ,  Mae Miller ,  Edward Unsworth ,  William Hook ,  Thomas Walsh ,  Karen Gray ,  Charles Macri

IPC分类号： A61K39/395 ,  A61K38/22

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。 中和AM生物活性的单克隆抗体MoAb-G6通过本发明的方法显示出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。

公开(公告)号：US07364719B2

公开(公告)日：2008-04-29

申请号：US10529118

申请日：2003-10-03

申请人： Frank Cuttitta ,  Alfredo Martinez ,  William G. Stetler-Stevenson ,  Edward J. Unsworth ,  Juan M. Saavedra

发明人： Frank Cuttitta ,  Alfredo Martinez ,  William G. Stetler-Stevenson ,  Edward J. Unsworth ,  Juan M. Saavedra

IPC分类号： A61K49/00

CPC分类号： A61K38/22 ,  A61K31/137 ,  G01N33/5088 ,  G01N2500/00

摘要： Methods and compounds are described for regulating blood pressure in a subject. Specific embodiments are methods for reversing vasodilation of blood vessels, by administering to a subject a therapeutically effective amount peptide AM(11-22). The vasoconstrictor can be used for a variety of purposes, including hemostasis or the treatment of shock, for example vasodilatory shock syndromes such as septic shock. Other specific embodiments are methods for reversing vasoconstriction of blood vessels, by administering to a subject a therapeutically effect amount of an inhibitor of AM(11-22), sufficient to reduce hypertension in the subject. Compounds and pharmaceutical compositions are also provided, as are kits.

摘要翻译： 描述了用于调节受试者血压的方法和化合物。 具体实施方案是通过向受试者施用治疗有效量的肽AM（11-22）来逆转血管的血管舒张的方法。 血管收缩剂可用于各种目的，包括止血或治疗休克，例如血管舒张性休克综合征，如脓毒性休克。 其他具体实施方案是通过向受试者施用足以降低受试者的高血压的治疗有效量的AM（11-22）抑制剂来逆转血管的血管收缩的方法。 还提供了化合物和药物组合物，试剂盒也是如此。

公开(公告)号：US07939639B2

公开(公告)日：2011-05-10

申请号：US12569821

申请日：2009-09-29

申请人： Frank Cuttitta ,  Alfredo Martinez ,  William A. Hook

发明人： Frank Cuttitta ,  Alfredo Martinez ,  William A. Hook

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。

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。

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

IPC分类号： G01N33/53 ,  A01N37/18 ,  A61K38/00 ,  C07K2/00 ,  C07K4/00 ,  C07K14/00 ,  C07K5/00 ,  C07K16/00

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。

公开(公告)号：US07462593B2

公开(公告)日：2008-12-09

申请号：US10529116

申请日：2003-11-07

申请人： Frank Cuttitta ,  Alfredo Martinez ,  William G. Stetler-Stevenson

发明人： Frank Cuttitta ,  Alfredo Martinez ,  William G. Stetler-Stevenson

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。

公开(公告)号：US07862815B2

公开(公告)日：2011-01-04

申请号：US12240656

申请日：2008-09-29

申请人： Frank Cuttitta ,  Alfredo Martinez ,  William G. Stetler-Stevenson

发明人： Frank Cuttitta ,  Alfredo Martinez ,  William G. Stetler-Stevenson

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。

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。