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：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。