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1. 发明授权

US06716410B1 Reagents and methods for diagnosing, imaging and treating atherosclerotic disease 失效
标题翻译：用于诊断，成像和治疗动脉粥样硬化疾病的试剂和方法
公开(公告)号：US06716410B1
公开(公告)日：2004-04-06
申请号：US09699131
申请日：2000-10-26
申请人： Joseph L. Witztum , Sotirios Tsimikas , Wulf Palinski , Peter X. Shaw
发明人： Joseph L. Witztum , Sotirios Tsimikas , Wulf Palinski , Peter X. Shaw
IPC分类号： A61K5100
CPC分类号： G01N33/92 , A61K41/0057 , A61K49/227 , A61K51/1018 , A61K2039/505 , C07K16/18 , C07K2317/21 , C07K2317/55 , C07K2317/622 , C07K2317/77 , G01N2800/323 , Y10S436/808 , Y10S436/809 , Y10S436/811 , Y10S530/807
摘要： The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.
摘要翻译：本发明提供了一种通过噬菌体展示法克隆的新型人类Mab Fab及其在诊断和治疗方法中的应用。特别地，本发明提供了一种用于分析体内动脉粥样硬化斑块的OxLDL组分的方法和用于确定其相对病理学的方法。由于该方法基于人Fab而不是小鼠Mab，所以随着时间的推移可以监测疾病的进展或消退。该抗体还可用于离体外分析外周血或血清样品以存在OxLDL。抗体还可以用于将治疗剂靶向动脉粥样硬化斑块的位点，或者可以用作治疗剂本身。

2. 发明授权

US07556927B2 Methods for diagnosing, imaging and treating atherosclerotic disease 失效
标题翻译：诊断，成像和治疗动脉粥样硬化疾病的方法
公开(公告)号：US07556927B2
公开(公告)日：2009-07-07
申请号：US10705448
申请日：2003-11-11
申请人： Joseph L. Witztum , Sotirios Tsimikas , Wulf Palinski , Peter X. Shaw
发明人： Joseph L. Witztum , Sotirios Tsimikas , Wulf Palinski , Peter X. Shaw
IPC分类号： G01N33/53
CPC分类号： G01N33/92 , A61K41/0057 , A61K49/227 , A61K51/1018 , A61K2039/505 , C07K16/18 , C07K2317/21 , C07K2317/55 , C07K2317/622 , C07K2317/77 , G01N2800/323 , Y10S436/808 , Y10S436/809 , Y10S436/811 , Y10S530/807
摘要： The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.
摘要翻译：本发明提供了一种通过噬菌体展示法克隆的新型人类Mab Fab及其在诊断和治疗方法中的应用。特别地，本发明提供了一种用于分析体内动脉粥样硬化斑块的OxLDL组分的方法和用于确定其相对病理学的方法。由于该方法基于人Fab而不是小鼠Mab，所以随着时间的推移可以监测疾病的进展或消退。该抗体还可用于离体外分析外周血或血清样品以存在OxLDL。抗体还可以用于将治疗剂靶向动脉粥样硬化斑块的位点，或者可以用作治疗剂本身。

3. 发明授权

US07575873B2 Reagents for diagnosing, imaging and treating atherosclerotic disease 失效
标题翻译：诊断，成像和治疗动脉粥样硬化疾病的试剂
公开(公告)号：US07575873B2
公开(公告)日：2009-08-18
申请号：US10706659
申请日：2003-11-12
申请人： Joseph L. Witztum , Sotirios Tsimikas , Wulf Palinski
发明人： Joseph L. Witztum , Sotirios Tsimikas , Wulf Palinski
IPC分类号： G01N33/563 , G01N33/53 , A61K39/395
CPC分类号： G01N33/92 , A61K41/0057 , A61K49/227 , A61K51/1018 , A61K2039/505 , C07K16/18 , C07K2317/21 , C07K2317/55 , C07K2317/622 , C07K2317/77 , G01N2800/323 , Y10S436/808 , Y10S436/809 , Y10S436/811 , Y10S530/807
摘要： The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.
摘要翻译：本发明提供了一种通过噬菌体展示法克隆的新型人类Mab Fab及其在诊断和治疗方法中的应用。特别地，本发明提供了一种用于分析体内动脉粥样硬化斑块的OxLDL组分的方法和用于确定其相对病理学的方法。由于该方法基于人Fab而不是小鼠Mab，所以随着时间的推移可以监测疾病的进展或消退。该抗体还可用于离体外分析外周血或血清样品以存在OxLDL。抗体还可以用于将治疗剂靶向动脉粥样硬化斑块的位点，或者可以用作治疗剂本身。

4. 发明授权

US06375925B1 Methods and reagents for non-invasive imaging of atherosclerotic plaque 失效
标题翻译：用于动脉粥样硬化斑块非侵入性成像的方法和试剂
公开(公告)号：US06375925B1
公开(公告)日：2002-04-23
申请号：US09381594
申请日：1999-11-22
申请人： Sotorios Tsimikas , Joseph L. Witztum , Wulf Palinski , Linda K. Curtis
发明人： Sotorios Tsimikas , Joseph L. Witztum , Wulf Palinski , Linda K. Curtis
IPC分类号： A61K5100
CPC分类号： A61K51/1027 , A61K51/1093
摘要： The invention provides reagents and methods for their use in in vivo diagnosis of atherosclerosis. In particular, the invention provides monoclonal antibodies which bind oxidation specific epitopes in atherosclerotic plaque lesions, such as those which occur in oxidized LDL, in vivo with high binding specificity; i.e., at about 10 to 20 times the rate of binding of the antibodies to adjacent normal arterial tissue. When detectably labeled and administered according to the invention, the antibodies are clearly imaged when bound to atherosclerotic plaque using known imaging techniques and devices, such as a gamma camera. In addition, the invention provides a method for substantially reducing interference from background signal in the blood pool into which such agents are introduced for detection and quantification of atherosclerotic plaque burden in the cardiovascular tissue of a host.
摘要翻译：本发明提供了用于动脉粥样硬化体内诊断的试剂和方法。特别地，本发明提供在动物粥样硬化斑块病变中结合氧化特异性表位的单克隆抗体，例如在氧化型LDL中发生的那些，具有高结合特异性; 即抗体相邻正常动脉组织结合速率的约10至20倍。当根据本发明可检测地标记和施用时，当使用已知的成像技术和装置（例如γ照相机）结合动脉粥样硬化斑块时，抗体清楚地成像。此外，本发明提供了一种用于基本上减少血库中背景信号的干扰的方法，其中引入这些药剂用于检测和定量主体心血管组织中的动脉粥样硬化斑块负荷。

5. 发明授权

US06225070B1 Antibodies to oxidation-specific epitopes on lipoprotein and methods for their use in detecting, monitoring and inhibiting the growth of atheroma 失效
标题翻译：对脂蛋白氧化特异性表位的抗体及其用于检测，监测和抑制动脉粥样化生长的方法
公开(公告)号：US06225070B1
公开(公告)日：2001-05-01
申请号：US08908746
申请日：1997-08-07
申请人： Joseph L. Witztum , Wulf Palinski , Sohvi Hörkkö , Daniel Steinberg
发明人： Joseph L. Witztum , Wulf Palinski , Sohvi Hörkkö , Daniel Steinberg
IPC分类号： G01N43571
CPC分类号： C07K16/18 , A61K38/00 , G01N33/92 , G01N2800/323
摘要： The invention relates to monoclonal antibodies which differentially bind oxidation-specific epitopes on lipoprotein in blood, arterial tissue and vascular tissue, including atherosclerotic plaque formed in arterial tissue and vascular tissue through lipoprotein oxidation. Methods for use of the antibodies in detecting and monitoring lipoprotein oxidation in vivo and in vitro are described, as are methods for inhibiting lipoprotein oxidation in vivo.
摘要翻译：本发明涉及通过脂蛋白氧化差异地结合血液，动脉组织和血管组织中的脂蛋白上的氧化特异性表位的单克隆抗体，包括在动脉组织和血管组织中形成的动脉粥样硬化斑块。还描述了在体内和体外检测和监测脂蛋白氧化中使用抗体的方法，以及抑制体内脂蛋白氧化的方法。

6. 发明授权

US08961982B2 Modulation of developmental immune programming and protection against cardiovascular disease, diabetes, infectious diseases, and cancer 有权
标题翻译：调控发育免疫规划和保护心血管疾病，糖尿病，传染病和癌症
公开(公告)号：US08961982B2
公开(公告)日：2015-02-24
申请号：US12139053
申请日：2008-06-13
申请人： Wulf Palinski , Tomoya Yamashita
发明人： Wulf Palinski , Tomoya Yamashita
IPC分类号： A61K39/00
CPC分类号： A61K39/0012 , A61K39/0008 , A61K2039/55 , A61K2039/6081
摘要： Maternal adaptive immunity conveys temporary humoral immune protection to neonates. The disclosure demonstrates the influence of the in utero environment on adult atherosclerosis and provides evidence for persistent effects of maternal immunization on adult immune responses. The disclosure provides methods and compositions useful for immunization and more particularly for actively modulating the fetal programming of the immune system for the purpose of preventing or treating immune-modulated diseases. The disclosure also provides interventions to protect offspring and immunized subjects against insulin resistance.
摘要翻译：产妇适应性免疫能够向新生儿传递临时体液免疫保护。本文揭示了子宫内环境对成年动脉粥样硬化的影响，并提供了母体免疫对成年免疫应答的持续影响的证据。本公开提供了用于免疫的方法和组合物，更具体地说是为了预防或治疗免疫调节疾病的目的，主动调节免疫系统的胎儿规划。本公开还提供了保护后代和免疫受试者免受胰岛素抵抗的干预。

7. 发明申请

US20080311152A1 MODULATION OF DEVELOPMENTAL IMMUNE PROGRAMMING AND PROTECTION AGAINST CARDIOVASCULAR DISEASE, DIABETES, INFECTIOUS DISEASES, AND CANCER 有权
标题翻译：发展性免疫球蛋白调控与心血管疾病，糖尿病，感染性疾病和癌症的保护
公开(公告)号：US20080311152A1
公开(公告)日：2008-12-18
申请号：US12139053
申请日：2008-06-13
申请人： Wulf Palinski , Tomoya Yamashita
发明人： Wulf Palinski , Tomoya Yamashita
IPC分类号： A61K39/12 , A61K39/00 , A61K39/02 , A61K39/002 , A61P37/04
CPC分类号： A61K39/0012 , A61K39/0008 , A61K2039/55 , A61K2039/6081
摘要： Maternal adaptive immunity conveys temporary humoral immune protection to neonates. The disclosure demonstrates the influence of the in utero environment on adult atherosclerosis and provides evidence for persistent effects of maternal immunization on adult immune responses. The disclosure provides methods and compositions useful for immunization and more particularly for actively modulating the fetal programming of the immune system for the purpose of preventing or treating immune-modulated diseases. The disclosure also provides interventions to protect offspring and immunized subjects against insulin resistance.
摘要翻译：产妇适应性免疫能够向新生儿传递临时体液免疫保护。本文揭示了子宫内环境对成年动脉粥样硬化的影响，并提供了母体免疫对成年免疫应答的持续影响的证据。本公开提供了用于免疫的方法和组合物，更具体地说是为了预防或治疗免疫调节疾病的目的，主动调节免疫系统的胎儿规划。本公开还提供了保护后代和免疫受试者免受胰岛素抵抗的干预。

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