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1. 发明授权

US06331408B1 Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production 有权
标题翻译：使用小分子放射性配体发现淀粉样蛋白-β肽生产的抑制剂
公开(公告)号：US06331408B1
公开(公告)日：2001-12-18
申请号：US09438901
申请日：1999-11-12
申请人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin Andrew Thompson
发明人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin Andrew Thompson
IPC分类号： C12Q137
CPC分类号： G01N33/6896 , G01N2333/4709 , G01N2500/02 , G01N2500/20 , G01N2800/2821 , Y10S435/968
摘要： This invention relates to a novel method of screening for inhibitors of beta-amyloid production, and thereby identifying such inhibitors as therapeutics for neurological and other disorders involving APP processing and beta-amyloid production. This invention also relates to identifying macromolecules involved in APP processing and beta-amyloid production. Furthermore, inhibitors identified by the screening method of the present invention are useful in the treatment of neurological disorders, such as Alzheimer's disease, which involve elevated levels of A&bgr; peptides.
摘要翻译：本发明涉及一种筛选β-淀粉样蛋白生成抑制剂的新方法，从而鉴定了诸如涉及APP加工和β-淀粉样蛋白生成的神经学和其它病症治疗剂的抑制剂。本发明还涉及鉴定参与APP处理和β-淀粉样蛋白生成的大分子。此外，通过本发明的筛选方法鉴定的抑制剂可用于治疗神经障碍，例如阿尔茨海默氏病，其涉及升高的Aβ肽水平。

2. 发明授权

US07153491B2 Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging 有权
标题翻译：使用小分子放射性配体发现淀粉样蛋白β肽生产抑制剂和诊断成像
公开(公告)号：US07153491B2
公开(公告)日：2006-12-26
申请号：US10734031
申请日：2003-12-11
申请人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin Andrew Thompson
发明人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin Andrew Thompson
IPC分类号： A61K49/00
CPC分类号： G01N33/6896 , G01N2333/4709 , G01N2500/02 , G01N2500/20 , G01N2800/2821
摘要： This invention relates to a novel method of screening for inhibitors of beta-amyloid production, and thereby identifying such inhibitors as therapeutics for neurological and other disorders involving APP processing and beta-amyloid production. This invention also relates to identifying macromolecules involved in APP processing and beta-amyloid production. Furthermore, inhibitors identified by the screening method of the present invention are useful in the treatment of neurological disorders, such as Alzheimer's disease, which involve elevated levels of Aβ peptides.
摘要翻译：本发明涉及一种筛选β-淀粉样蛋白生成抑制剂的新方法，从而鉴定了诸如涉及APP加工和β-淀粉样蛋白生成的神经学和其它病症治疗剂的抑制剂。本发明还涉及鉴定参与APP处理和β-淀粉样蛋白生成的大分子。此外，通过本发明的筛选方法鉴定的抑制剂可用于治疗神经障碍，例如阿尔茨海默氏病，其涉及升高的Aβ肽水平。

3. 发明授权

US06878363B2 Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging 失效
标题翻译：使用小分子放射性配体发现淀粉样蛋白β肽生产抑制剂和诊断成像
公开(公告)号：US06878363B2
公开(公告)日：2005-04-12
申请号：US09859261
申请日：2001-05-17
申请人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin A. Thompson
发明人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin A. Thompson
IPC分类号： A61K51/08 , A61K51/00 , A61M36/14
CPC分类号： A61K51/0468
摘要： A method of using radiolabelled and/or radiopharmaceutical small molecule inhibitors of beta-amyloid peptide production for the diagnosis of neurological and other disorders involving APP processing and beta-amyloid production. Radiolabelled small molecule inhibitors identified by the methods of the present invention would be useful in the diagnosis of neurological disorders, such as Alzheimer's disease, which involve elevated levels of Aβ peptides.
摘要翻译：使用放射性标记和/或放射性药物小分子抑制剂β-淀粉样蛋白肽生产的方法用于诊断涉及APP加工和β-淀粉样蛋白生成的神经和其他疾病。通过本发明方法鉴定的放射性标记的小分子抑制剂可用于诊断涉及升高水平的Aβ肽的神经障碍，例如阿尔茨海默氏病。

4. 发明授权

US07709646B2 Tetrahydroquinoline derivatives useful as serine protease inhibitors 有权
标题翻译：用作丝氨酸蛋白酶抑制剂的四氢喹啉衍生物
公开(公告)号：US07709646B2
公开(公告)日：2010-05-04
申请号：US11430588
申请日：2006-05-09
申请人： Mimi L. Quan , Cailan Wang , Jinglan Zhou , Jon J. Hangeland , Dietmar A. Seiffert , Robert M. Knabb
发明人： Mimi L. Quan , Cailan Wang , Jinglan Zhou , Jon J. Hangeland , Dietmar A. Seiffert , Robert M. Knabb
IPC分类号： C07D215/38
CPC分类号： C07D401/12 , C07D215/12 , C07D215/20 , C07D215/48
摘要： The present invention provides compounds of Formula (I): or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4, R4, R5, R13, R14, R15 and R16 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
摘要翻译：本发明提供式（I）化合物或其立体异构体或药学上可接受的盐形式，其中变量A，B，L1，L2，X1，X2，X3，X4，R4，R5，R13，R14，R15和 R 16如本文所定义。式（I）的化合物可用作凝血级联和/或接触激活系统的丝氨酸蛋白酶的选择性抑制剂; 例如凝血酶，因子Xa，因子XIa，因子IXa，因子VIIa和/或血浆激肽释放酶。特别地，它涉及作为选择性因子XIa抑制剂的化合物。本发明还涉及包含这些化合物的药物组合物和使用其制备血栓栓塞和/或炎症性疾病的方法。

5. 发明授权

US07049138B2 Epitope-tagged beta-amyloid precursor protein and DNA encoding the same 有权
标题翻译：表位标记的β-淀粉样蛋白前体蛋白和编码相同的DNA
公开(公告)号：US07049138B2
公开(公告)日：2006-05-23
申请号：US10326049
申请日：2002-12-20
申请人： Dietmar A. Seiffert , Thomas J. Mitchell
发明人： Dietmar A. Seiffert , Thomas J. Mitchell
IPC分类号： C07K2/00 , C07K14/00 , C07H21/04 , C12N5/00 , C12N15/62
CPC分类号： C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2500/00 , G01N2500/10 , G01N2800/2821
摘要： The present invention is directed generally to methods and composition for monitoring the processing of epitope-tagged beta-APP. More specifically, the present invention relates to the use of such methods and composition for monitoring responses of cells expressing such epitope-tagged beta-APP or fragments thereof or cell free systems containing the epitope-tagged polypeptides to therapy of diseases associated with an altered metabolism of the beta amyloid precursor protein (APP), and for screening and evaluation of potential drugs for the treatment of these disorders, including Alzheimer's disease (AD).
摘要翻译：本发明一般涉及用于监测表位标记的β-APP的加工的方法和组合物。更具体地，本发明涉及这些方法和组合物用于监测表达这种表位标记的β-APP或其片段的细胞的应答或含有表位标记的多肽的无细胞系统用于治疗与代谢改变相关的疾病的反应的用途的β淀粉样蛋白前体蛋白（APP），以及用于筛选和评估用于治疗这些疾病（包括阿尔茨海默氏病（AD））的潜在药物。

6. 发明授权

US06737038B1 Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging 有权
标题翻译：使用小分子放射性配体发现淀粉样蛋白β肽生产抑制剂和诊断成像
公开(公告)号：US06737038B1
公开(公告)日：2004-05-18
申请号：US09573789
申请日：2000-05-17
申请人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin A. Thompson
发明人： Robert Zaczek , Richard E. Olson , Dietmar A. Seiffert , Lorin A. Thompson
IPC分类号： A61K4900
CPC分类号： G01N33/6896 , G01N2333/4709 , G01N2500/02 , G01N2500/20 , G01N2800/2821
摘要： This invention relates to a novel method of screening for inhibitors of beta-amyloid production, and thereby identifying such inhibitors as therapeutics for neurological and other disorders involving APP processing and beta-amyloid production. This invention also relates to identifying macromolecules involved in APP processing and beta-amyloid production. Furthermore, inhibitors identified by the screening method of the present invention are useful in the treatment of neurological disorders, such as Alzheimer's disease, which involve elevated levels of A&bgr; peptides.
摘要翻译：本发明涉及一种筛选β-淀粉样蛋白生成抑制剂的新方法，从而鉴定了诸如涉及APP加工和β-淀粉样蛋白生成的神经学和其它病症治疗剂的抑制剂。本发明还涉及鉴定参与APP处理和β-淀粉样蛋白生成的大分子。此外，通过本发明的筛选方法鉴定的抑制剂可用于治疗神经障碍，例如阿尔茨海默氏病，其涉及升高的Aβ肽水平。

7. 发明授权

US06623981B2 Detection of patients at risk for developing integrin antagonist/agonist mediated disease states 有权
标题翻译：检测患有发展为整合素拮抗剂/激动剂介导的疾病状态的患者
公开(公告)号：US06623981B2
公开(公告)日：2003-09-23
申请号：US09237061
申请日：1999-01-26
申请人： Jeffrey T. Billheimer , Dietmar A. Seiffert , Leah A. Breth , Timothy C. Burn , Ira B. Dicker , Henry J. George , Gregory F. Hollis , Jeannine M. Hollis , Jennifer E. Kochie , Karyn T. O'Neil
发明人： Jeffrey T. Billheimer , Dietmar A. Seiffert , Leah A. Breth , Timothy C. Burn , Ira B. Dicker , Henry J. George , Gregory F. Hollis , Jeannine M. Hollis , Jennifer E. Kochie , Karyn T. O'Neil
IPC分类号： G01N33553
CPC分类号： G01N33/6893 , C07K14/70557 , C07K16/2848 , G01N33/566 , G01N33/68 , G01N2333/70546 , G01N2500/00 , Y10S435/968 , Y10S436/811
摘要： This invention relates to the detection of patients at risk for developing integrin antagonist/agonist mediated disease states. This invention relates to assays useful for the detection in a patient bodily fluid sample of drug-dependent antibodies which bind to integrins, or intergrin-associated proteins or complexes thereof in the presence of an integrin antagonist/agonist. This invention also relates to assays useful for the detection in a patient bodily fluid sample of drug-dependent antibodies (DDABS) that bind to integrins, including the platelet glycoprotein IIb/IIIa (GPIIb/IIIa), in the presence of a integrin agonist and/or antagonist. This invention also relates to procedures for identifying integrin antagonists/agonists that are less prone to elicit integrin antagonist/agonist mediated disease states. This invention also relates to procedures which increase the recovery of integrin-directed antibodies in body fluids, resulting in an increased sensitivity and specificity of DDAB detection assays. This invention also relates to procedures for treating blood samples, which dissociate antibodies to GPIIb/IIIa from the platelet surface, thereby increasing the recovery from the platelet supernatant. This invention also relates to the use of different GPIIb/IIIa preparations to identify patients at risk for early-onset thrombocytopenia upon treatment with GPIIb/IIIa antagonist/agonists, thereby increasing the specificity of antibody detection. This invention also relates to the use of DDABs as a positive control and calibration standard for DDAB assays. Such methods, procedures and assays are useful for identifying patients who may be at risk to develop disease states mediated by treatment with integrin antagonists/agonists.
摘要翻译：本发明涉及检测发展为整合素拮抗剂/激动剂介导的疾病状态的风险的患者。本发明涉及可用于在整联蛋白拮抗剂/激动剂存在下结合整联蛋白或整合蛋白相关蛋白或其复合物的药物依赖性抗体的患者体液样品中的检测。本发明还涉及用于在整联蛋白激动剂存在下结合整联蛋白（包括血小板糖蛋白IIb / IIIa（GPIIb / IIIa））的药物依赖性抗体（DDABS）的患者体液样品中检测的测定法， /或拮抗剂。本发明还涉及识别不易引起整联蛋白拮抗剂/激动剂介导的疾病状态的整联蛋白拮抗剂/激动剂的方法。本发明还涉及增加体液中整联蛋白定向抗体的回收率的方法，导致敏感性增加和DDAB检测测定的特异性。本发明还涉及用于治疗血液样品的方法，其从血小板表面解离GPIIb / IIIa的抗体，从而增加血小板上清液的回收。本发明还涉及使用不同的GPIIb / IIIa制剂来鉴定在用GPIIb / IIIa拮抗剂/激动剂治疗时患有早发性血小板减少症的患者，从而增加抗体检测的特异性。本发明还涉及使用DDAB 作为DDAB测定的阳性对照和校准标准。这些方法，程序和测定法可用于鉴定可能患有通过用整联蛋白拮抗剂/激动剂治疗介导的疾病状态的风险的患者。

8. 发明授权

US06518011B1 Method for screening compounds to identify beta-amyloid production modulators 有权
标题翻译：筛选化合物以鉴定β-淀粉样蛋白生成调节剂的方法
公开(公告)号：US06518011B1
公开(公告)日：2003-02-11
申请号：US09481980
申请日：2000-01-12
申请人： Dietmar A. Seiffert , Thomas J. Mitchell
发明人： Dietmar A. Seiffert , Thomas J. Mitchell
IPC分类号： C07K100
CPC分类号： C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2500/00 , G01N2500/10 , G01N2800/2821
摘要： The present invention is directed generally to methods and composition for monitoring the processing of epitope-tagged beta-APP. More specifically, the present invention relates to the use of such methods and composition for monitoring responses of cells expressing such epitope-tagged beta-APP or fragments thereof or cell free systems containing the epitope-tagged polypeptides to therapy of diseases associated with an altered metabolism of the beta amyloid precursor protein (APP), and for screening and evaluation of potential drugs for the treatment of these disorders, including Alzheimer's disease (AD).
摘要翻译：本发明一般涉及用于监测表位标记的β-APP的加工的方法和组合物。更具体地，本发明涉及这些方法和组合物用于监测表达这种表位标记的β-APP或其片段的细胞的应答或含有表位标记的多肽的无细胞系统用于治疗与代谢改变相关的疾病的反应的用途的β淀粉样蛋白前体蛋白（APP），以及用于筛选和评估用于治疗这些疾病（包括阿尔茨海默氏病（AD））的潜在药物。

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