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1. 发明授权

US07101548B2 Functional role of adrenomedullin (AM) and the gene-related product (PAMP) in human pathology and physiology 有权
标题翻译：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：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。

2. 发明申请

US20100021469A1 FUNCTIONAL ROLE OF ADRENOMEDULLIN (AM) AND THE GENE RELATED PRODUCT (PAMP) IN HUMAN PATHOLOGY AND PHYSIOLOGY 有权
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：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。

3. 发明授权

US06320022B1 Adrenomedullin peptides 失效
标题翻译：肾上腺髓质素（am）和基因相关产品（pamp）在人类病理和动力学中的功能作用
公开(公告)号：US06320022B1
公开(公告)日：2001-11-20
申请号：US09011922
申请日：1998-02-17
申请人： Frank Cutitta , Alfredo Martinez , Mae Jean Miller , Edward J. Unsworth , William Hook , Thomas Walsh , Karen Gray , Charles Macri
发明人： Frank Cutitta , Alfredo Martinez , Mae Jean Miller , Edward J. Unsworth , William Hook , Thomas Walsh , Karen Gray , Charles Macri
IPC分类号： A61K3800
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。

4. 发明授权

US07364719B2 Vasoregulating compounds and methods of their use 失效
标题翻译：减压化合物及其使用方法
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。

5. 发明申请

US20120294870A1 COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF TUMORS 失效
标题翻译：用于诊断和治疗肿瘤的组合物和方法
公开(公告)号：US20120294870A1
公开(公告)日：2012-11-22
申请号：US13549633
申请日：2012-07-16
申请人： Vivian Takafuji , Xin Wei Wang , Edward J. Unsworth , Paul K. Goldsmith
发明人： Vivian Takafuji , Xin Wei Wang , Edward J. Unsworth , Paul K. Goldsmith
IPC分类号： C07K16/24 , A61K39/395 , C40B30/00 , G01N33/566 , C12Q1/68 , C12N5/18 , G01N33/577 , G01N21/76 , C12N15/13 , C12N15/63 , C12N1/21 , C12N1/19 , C12N5/10 , A61P35/00 , C12N5/09
CPC分类号： C07K16/2848 , A61K38/00 , A61K2039/505 , C07K16/18 , C07K16/24 , C07K16/2884 , C07K16/40 , C07K2317/76 , G01N33/57438 , G01N33/57484 , G01N2333/52
摘要： Based on the observation of the cooperation of osteopontin (OPN) and matrixmetalloproteinase-9 (MMP-9) in the promotion of the metastatic phenotype, therapies and diagnostic assays are disclosed for the treatment of a tumor that overexpresses OPN, such as hepatocellular carcinoma (HCC), for example metastatic HCC. In one example, methods of treating a tumor include administration of an agent that reduces cellular invasion resulting from the interaction between a fragment of OPN (OPN-5kD) generated by MMP-9 cleavage and CD44 receptor. Examples of such agents include fragments of OPN-5kD and antibodies specific for OPN-5kD. Therapeutic compositions are also provided that include such agents. Also provided are methods of diagnosing or prognosing a tumor, for example by detecting expression of OPN-5kD peptide or OPN-c mRNA in a biological sample obtained from the subject. Also provided are antibodies that specifically bind OPN-5kD.
摘要翻译：基于骨桥蛋白（OPN）和基质金属蛋白酶-9（MMP-9）在促进转移表型中的合作观察，公开了治疗和过度表达OPN的肿瘤如肝细胞癌（ HCC），例如转移性HCC。在一个实例中，治疗肿瘤的方法包括施用减少由MMP-9切割产生的OPN片段（OPN-5kD）与CD44受体之间的相互作用而引起的细胞侵袭的药剂。这些试剂的实例包括OPN-5kD片段和OPN-5kD特异性抗体。还提供包括这些试剂的治疗组合物。还提供了诊断或预后肿瘤的方法，例如通过检测从受试者获得的生物样品中OPN-5kD肽或OPN-cmRNA的表达。还提供了特异性结合OPN-5kD的抗体。

6. 发明授权

US06802967B2 Multi-dimension liquid chromatography separation system 有权
标题翻译：多维液相色谱分离系统
公开(公告)号：US06802967B2
公开(公告)日：2004-10-12
申请号：US10091029
申请日：2002-03-06
申请人： Junichi Masuda , Edward J. Unsworth , Jeffrey A. Kowalak , Sanford P. Markey
发明人： Junichi Masuda , Edward J. Unsworth , Jeffrey A. Kowalak , Sanford P. Markey
IPC分类号： B01D1508
CPC分类号： G01N30/463 , G01N30/02 , G01N30/34 , G01N2030/8411 , B01D15/361 , B01D15/325 , B01D15/242
摘要： Liquid chromatography based on the difference of two or more kinds of separation modes, (e.g., chemical or physical properties of analytes) may improve separations when samples contain complex mixtures. In this invention, the analytes separated on the 1st analysis system (consisting of the 1st column and the 1st mobile phase) will be trapped onto individual trapping columns. Then the trapped analytes will be loaded onto the 2nd analysis system consisting of the 2nd column and the 2nd mobile phase. This invention has the trapping and loading mechanism consisting of a combination of switching valves necessary to produce the serial separations. Also this invention has the capability to affect online desalting when it is needed depending on a detector or the nature of the analyte mixture.
摘要翻译：基于两种或更多种分离模式的差异（例如分析物的化学或物理性质）的液相色谱可以在样品含有复杂混合物时改善分离。在本发明中，在第一分析系统（由第一列和第一流动相组成）上分离的分析物将被捕获到各个捕集柱上。然后将被捕获的分析物加载到由第二列和第二流动相组成的第二分析系统上。本发明具有由产生串联分离所必需的切换阀组合的捕集和加载机构。此外，根据检测器或分析物混合物的性质，本发明还具有影响在线脱盐的能力。

7. 发明申请

US20090136524A1 COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF TUMORS 有权
标题翻译：用于诊断和治疗肿瘤的组合物和方法
公开(公告)号：US20090136524A1
公开(公告)日：2009-05-28
申请号：US12340211
申请日：2008-12-19
申请人： Vivian Takafuji , Xin Wei Wang , Edward J. Unsworth , Paul K. Goldsmith
发明人： Vivian Takafuji , Xin Wei Wang , Edward J. Unsworth , Paul K. Goldsmith
IPC分类号： A61K39/395 , G01N33/68 , G01N33/53 , C12Q1/02 , A61K38/10 , C07K14/435 , C07H21/00 , A61P35/00 , C12N15/63 , C07K16/00 , A61K38/17 , A61K38/08 , C12Q1/68 , C12N5/00
CPC分类号： C07K16/2848 , A61K38/00 , A61K2039/505 , C07K16/18 , C07K16/24 , C07K16/2884 , C07K16/40 , C07K2317/76 , G01N33/57438 , G01N33/57484 , G01N2333/52
摘要： Based on the observation of the cooperation of osteopontin (OPN) and matrixmetalloproteinase-9 (MMP-9) in the promotion of the metastatic phenotype, therapies and diagnostic assays are disclosed for the treatment of a tumor that overexpresses OPN, such as hepatocellular carcinoma (HCC), for example metastatic HCC. In one example, methods of treating a tumor include administration of an agent that reduces cellular invasion resulting from the interaction between a fragment of OPN (OPN-5kD) generated by MMP-9 cleavage and CD44 receptor. Examples of such agents include fragments of OPN-5 kD and antibodies specific for OPN-5kD. Therapeutic compositions are also provided that include such agents. Also provided are methods of diagnosing or prognosing a tumor, for example by detecting expression of OPN-5kD peptide or OPN-c mRNA in a biological sample obtained from the subject. Also provided are antibodies that specifically bind OPN-5kD.
摘要翻译：基于骨桥蛋白（OPN）和基质金属蛋白酶-9（MMP-9）在促进转移表型中的合作观察，公开了治疗和过度表达OPN的肿瘤如肝细胞癌（ HCC），例如转移性HCC。在一个实例中，治疗肿瘤的方法包括施用减少由MMP-9切割产生的OPN片段（OPN-5kD）与CD44受体之间的相互作用而引起的细胞侵袭的药剂。这些试剂的实例包括OPN-5kD片段和OPN-5kD特异性抗体。还提供包括这些试剂的治疗组合物。还提供了诊断或预后肿瘤的方法，例如通过检测从受试者获得的生物样品中OPN-5kD肽或OPN-cmRNA的表达。还提供了特异性结合OPN-5kD的抗体。

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