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1. 发明授权

US06251852B1 Combination therapy for reducing the risks associated with cardiovascular disease 失效
标题翻译：联合治疗减少与心血管疾病相关的风险
公开(公告)号：US06251852B1
公开(公告)日：2001-06-26
申请号：US08929595
申请日：1997-09-15
申请人： Robert J. Gould , Steven A. Nichtberger , Patricia A. Rhymer , Lars Olofsson
发明人： Robert J. Gould , Steven A. Nichtberger , Patricia A. Rhymer , Lars Olofsson
IPC分类号： A61K3800
CPC分类号： A61K45/06
摘要： The instant invention involves a combination therapy and pharmaceutical compositions comprised of a therapeutically effective amount of a cholesterol reducing agent such as an HMG-CoA reductase inhibitor in combination with a platelet aggregation inhibitor which is useful for inhibiting platelet aggregation, for inhibiting the formation of thrombotic occlusions, and for treating, preventing and reducing the risk of occurrence of cardiovascular and cerebrovascular events and related vaso-occlusive disorders.
摘要翻译：本发明涉及组合疗法和药物组合物，其包含治疗有效量的胆固醇降低剂如HMG-CoA还原酶抑制剂与可用于抑制血小板聚集的血小板聚集抑制剂的组合，用于抑制血栓形成闭塞，并用于治疗，预防和降低心血管和脑血管事件发生的风险以及相关的血管闭塞障碍。

2. 发明授权

US06235706B1 Combination therapy for reducing the risks associated with cardiovascular disease 失效
标题翻译：联合治疗减少与心血管疾病相关的风险
公开(公告)号：US06235706B1
公开(公告)日：2001-05-22
申请号：US09147858
申请日：1999-05-27
申请人： Robert J. Gould , Steven A. Nichtberger , Patricia A. Rhymer , Lars Olofsson
发明人： Robert J. Gould , Steven A. Nichtberger , Patricia A. Rhymer , Lars Olofsson
IPC分类号： A61K3800
CPC分类号： A61K45/06
摘要： The present invention involves a combination therapy of administering a cholesterol reducing agent, such as a 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitor and a platelet aggregation inhibitor for treating, preventing or reducing the risk of developing cardiovascular and cerebrovascular events and disorders in a mammal.
摘要翻译：本发明涉及施用胆固醇降低剂如3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂和血小板聚集抑制剂的组合疗法，用于治疗，预防或降低发展心血管的风险，哺乳动物的脑血管事件和病症。

3. 发明授权

US06403571B2 Combination therapy for reducing the risks associated with cardiovascular disease 失效
标题翻译：联合治疗减少与心血管疾病相关的风险
公开(公告)号：US06403571B2
公开(公告)日：2002-06-11
申请号：US09764511
申请日：2001-01-18
申请人： Robert J. Gould , Steven A. Nichtberger , Patricia A. Rhymer , Lars Olofsson
发明人： Robert J. Gould , Steven A. Nichtberger , Patricia A. Rhymer , Lars Olofsson
IPC分类号： A61K3152
CPC分类号： A61K45/06
摘要： The instant invention involves a combination therapy and pharmaceutical compositions comprised of a therapeutically effective amount of a cholesterol reducing agent such as an HMG-CoA reductase inhibitor in combination with a platelet aggregation inhibitor which is useful for inhibiting platelet aggregation, for inhibiting the formation of thrombotic occlusions, and for treating, preventing and reducing the risk of occurrence of cardiovascular and cerebrovascular events and related vaso-occlusive disorders.
摘要翻译：本发明涉及组合疗法和药物组合物，其包含治疗有效量的胆固醇降低剂如HMG-CoA还原酶抑制剂与可用于抑制血小板聚集的血小板聚集抑制剂的组合，用于抑制血栓形成闭塞，并用于治疗，预防和降低心血管和脑血管事件发生的风险以及相关的血管闭塞障碍。

4. 发明授权

US06136794A Platelet aggregation inhibition using low molecular weight heparin in combination with a GP IIb/IIIa antagonist 有权
标题翻译：使用低分子量肝素与GP IIb / IIIa拮抗剂组合的血小板聚集抑制
公开(公告)号：US06136794A
公开(公告)日：2000-10-24
申请号：US240429
申请日：1999-01-29
申请人： Jacquelynn J. Cook , Robert J. Gould , Frederic L. Sax
发明人： Jacquelynn J. Cook , Robert J. Gould , Frederic L. Sax
IPC分类号： A61K45/06 , A61K31/725
CPC分类号： A61K31/727 , A61K45/06
摘要： A method for inhibiting platelet aggregation in a mammal comprising administering to the mammal a safe and therapeutically effective amount of a GPIIb/IIIa receptor antagonist or a pharmaceutically acceptable salt thereof and a safe and therapeutically effective amount of low molecular weight heparin. A method for inhibiting platelet aggregation in a mammal comprising administering to the mammal a safe and therapeutically effective amount of (2-S-(n-butylsulfonylamino)-3[4-(piperidin-4-yl)butyloxyphenyl]-propionic acid or a pharmaceutically acceptable salt thereof and a safe and therapeutically effective amount of low molecular weight heparin.
摘要翻译：一种用于抑制哺乳动物血小板聚集的方法，包括向哺乳动物施用安全和治疗有效量的GPIIb / IIIa受体拮抗剂或其药学上可接受的盐以及安全和治疗有效量的低分子量肝素。一种用于抑制哺乳动物血小板聚集的方法，包括向哺乳动物施用安全和治疗有效量的（2-S-（正丁基磺酰基氨基）-3 [4-（哌啶-4-基）丁氧基苯基] - 丙酸或其药学上可接受的盐和安全和治疗有效量的低分子量肝素。

5. 发明授权

US06210904B1 Anticoagulant test 失效
标题翻译：抗凝血试验
公开(公告)号：US06210904B1
公开(公告)日：2001-04-03
申请号：US09170858
申请日：1998-10-13
申请人： Bohumil Bednar , Daniel M. Bollag , Robert J. Gould
发明人： Bohumil Bednar , Daniel M. Bollag , Robert J. Gould
IPC分类号： G01N3353
CPC分类号： C07K16/2848 , A61K38/00 , C07K2317/24 , G01N33/68 , G01N33/6893 , G01N2333/70557
摘要： The present invention is a method for diagnosing a patient at risk to thrombocytopenia induced by administration of a GP IIb/IIIa receptor antagonist, which comprises combining i) a plasma sample of the patient; ii) detectable monoclonal antibody which recognizes induced binding sites formed on the GP IIb/IIIa receptor following association of a fibrinogen receptor antagonist with the GP IIb/IIIa receptor; and iii) GP IIb/IIIa receptor:GP IIb/III receptor antagonist complex, and determining association of the detectable monoclonal antibody with the complex in the presence of the plasma.
摘要翻译：本发明是一种用于诊断通过给予GP IIb / IIIa受体拮抗剂诱导的血小板减少症的患者的方法，所述方法包括组合患者的血浆样品; ii）识别诱导结合位点上形成的诱导结合位点的可检测单克隆抗体 GP IIb / IIIa受体与纤维蛋白原受体拮抗剂与GP IIb / IIIa受体结合后，和ii）GP IIb / IIIa受体：GP IIb / III受体拮抗剂复合物，以及在血浆存在下确定可检测单克隆抗体与复合物的缔合。

6. 发明授权

US5646000A Compounds and methods for identifying activated platelets 失效
标题翻译：用于鉴定活化血小板的化合物和方法
公开(公告)号：US5646000A
公开(公告)日：1997-07-08
申请号：US315034
申请日：1994-09-29
申请人： Bohumil Bednar , Melissa Egbertson , Robert J. Gould , George D. Hartman , Jules A. Shafer
发明人： Bohumil Bednar , Melissa Egbertson , Robert J. Gould , George D. Hartman , Jules A. Shafer
IPC分类号： C07D401/06 , C07D405/14 , C07D491/22 , C07D495/04 , G01N33/569 , G01N33/80 , G01N33/86 , G01N33/567 , C07D401/14
CPC分类号： C07D401/06 , C07D405/14 , C07D495/04 , G01N33/56966 , G01N33/80 , G01N33/86 , G01N2500/00 , Y10S436/80 , Y10S436/811
摘要： The invention is directed to a series of novel compounds, and their pharmaceutically acceptable salts, of the formula ##STR1## wherein R is C.sub.0-6 alkyl substituted with R.sup.5 or a mono or polycyclic aromatic or heteroaromatic system comprised of 5 or 6-membered aromatic or heteroaromatic rings that are either unsubstituted or substituted with one or more of R.sup.1 and R.sup.2 ; R.sup.1 and R.sup.2 are independently C.sub.1-6 alkyl, carboxyl, hydroxyl, azido, nitro, amino, C.sub.1-6 alkylamino, C.sub.1-6 dialkylamino, arylamino, aryl C.sub.1-6 alkylamino, hydroxysulfonyl or arylazo; aryl is a phenyl or naphthyl ring which is unsubstituted or substituted with one or more of R.sup.3 and R.sup.4 ; R.sup.3 and R.sup.4 are independently C.sub.1-6 alkyl, azido, nitro, amino, C.sub.1-6 dialkylamino or hydroxysulfonyl; R.sup.5 is ##STR2## provided that when R is an unsubstituted monocyclic ring, the monocyclic ring is not phenyl or pyridyl. Such compounds are useful as fluorescent probes for identifying antiplatelet agents which selectively bind to activated platelets.
摘要翻译：本发明涉及一系列新颖的化合物及其药学上可接受的盐，其中R是被R 5取代的C 1-6烷基或由5或6元芳族的单或多环芳族或杂芳族体系或未被取代或被一个或多个R 1和R 2取代的杂芳环; R 1和R 2独立地是C 1-6烷基，羧基，羟基，叠氮基，硝基，氨基，C 1-6烷基氨基，C 1-6二烷基氨基，芳基氨基，芳基C 1-6烷基氨基，羟基磺酰基或芳基偶氮; 芳基是未被取代或被一个或多个R 3和R 4取代的苯基或萘基环; R 3和R 4独立地为C 1-6烷基，叠氮基，硝基，氨基，C 1-6二烷基氨基或羟基磺酰基; R5是或，条件是当R是未取代的单环时，单环不是苯基或吡啶基。这样的化合物可用作识别选择性结合活化血小板的抗血小板剂的荧光探针。

7. 发明申请

US20100120750A1 METHODS FOR INDUCING POLYPLOIDIZATION OF MEGAKARYOCYTES AND FOR TREATING BLOOD AND BONE MARROW DISEASES AND DISORDERS 有权
标题翻译：诱导多糖的多分支化合物和治疗血液和骨髓疾病和疾病的方法
公开(公告)号：US20100120750A1
公开(公告)日：2010-05-13
申请号：US12613996
申请日：2009-11-06
申请人： John D. Crispino , Qiang Wen , Zan Huang , Andrew M. Stern , Robert J. Gould
发明人： John D. Crispino , Qiang Wen , Zan Huang , Andrew M. Stern , Robert J. Gould
IPC分类号： A61K31/5513 , C12N5/071 , C12N5/02 , A61K31/4439 , A61P7/00
CPC分类号： A61K31/5513 , A61K31/551
摘要： Disclosed are methods for inducing polyploidization of megakaryocyte cells and for promoting differentiation of megakaryocyte cells into platelet-producing cells. The methods may be utilized for treating blood and bone marrow diseases and disorders in a subject in need thereof and for identifying agents for treating blood and bone marrow diseases and disorders.
摘要翻译：公开了诱导巨核细胞多倍体化和促进巨核细胞分化成血小板产生细胞的方法。该方法可用于治疗有需要的受试者中的血液和骨髓疾病和病症，以及用于鉴定用于治疗血液和骨髓疾病和病症的药剂。

8. 发明申请

US20090007283A1 Transgenic Rodents Selectively Expressing Human B1 Bradykinin Receptor Protein 审中-公开
标题翻译：转基因啮齿动物选择性表达人B1缓激肽受体蛋白
公开(公告)号：US20090007283A1
公开(公告)日：2009-01-01
申请号：US10573926
申请日：2004-10-04
申请人： John W. Hess , Robert J. Gould , Douglas J. Pettibone , Thomas F. Vogt , Richard Z. Chen
发明人： John W. Hess , Robert J. Gould , Douglas J. Pettibone , Thomas F. Vogt , Richard Z. Chen
IPC分类号： A01K67/027
CPC分类号： A01K67/0275 , A01K2207/15 , A01K2217/00 , A01K2217/072 , A01K2227/105 , A01K2267/03 , C07K14/705 , C12N15/8509
摘要： Non-human transgenic animals, such as transgenic mice, are generated which incorporate the a non-native form of the bradykinin B1 receptor gene against a null phenotype for the native form of the bradykinin B1 receptor. An exemplified portion of the invention disclosed a transgenic mouse wherein a targeting construct containing a transgene encoding the human B1 bradykinin receptor gene is inserted downstream of and operatively linked to the native mice bradykinin B1 promoter. This targeting construct also contains a fluxed neomycin resistance gene. The resulting transgenic animals are “humanized” for the bradykinin B1 receptor and are effectively on a null background for native, functional B1 receptor activity. These animals may be crossed with a Cre-deleter strain to generate transgenic offspring which absent of the floxed marker gene. The transgenic animals described herein provide for a model to The transgenic mice of the present invention provide for an animal model enabling the analysis of compounds that are selective for the human B1 bradykinin receptor, relative to the rodent (e.g., rat or mouse) B1 bradykinin receptor.
摘要翻译：产生非人转基因动物，例如转基因小鼠，其掺入缓激肽B1受体基因的非天然形式针对天然形式的缓激肽B1受体的无效表型。本发明的示例性部分公开了一种转基因小鼠，其中含有编码人B1缓激肽受体基因的转基因的靶向构建体插入天然小鼠缓激肽B1启动子的下游并与之有效连接。该靶向构建体还含有一种助溶的新霉素抗性基因。所得到的转基因动物对于缓激肽B1受体是“人源化的”，并且对于天然的功能性B1受体活性而言，其无效背景是有效的。这些动物可以与Cre-去除菌株杂交以产生不含斑点标记基因的转基因后代。本文所述的转基因动物提供了本发明的转基因小鼠相对于啮齿动物（例如大鼠或小鼠）B1缓激肽提供能够分析对人B1缓激肽受体有选择性的化合物的动物模型的模型受体。

9. 发明授权

US06538112B2 Hybridomas and monoclonal antibodies for an anticoagulant test 失效
标题翻译：用于抗凝血试验的杂交瘤和单克隆抗体
公开(公告)号：US06538112B2
公开(公告)日：2003-03-25
申请号：US09823444
申请日：2001-03-30
申请人： Bohumil Bednar , Daniel M. Bollag , Robert J. Gould
发明人： Bohumil Bednar , Daniel M. Bollag , Robert J. Gould
IPC分类号： C07K1600
CPC分类号： C07K16/2848 , A61K38/00 , C07K2317/24 , G01N33/68 , G01N33/6893 , G01N2333/70557
摘要： The present invention is a method for diagnosing a patient at risk to thrombocytopenia induced by administration of a GP IIb/IIIa receptor antagonist, which comprises combining i) a plasma sample of the patient; ii) detectable monoclonal antibody which recognizes induced binding sites formed on the GP IIb/IIIa receptor following association of a fibrinogen receptor antagonist with the GP IIb/IIIa receptor; and iii) GP IIb/IIIa receptor:GP IIb/III receptor antagonist complex, and determining association of the detectable monoclonal antibody with the complex in the presence of the plasma.
摘要翻译：本发明是一种用于诊断通过给予GP IIb / IIIa受体拮抗剂诱导的血小板减少症的患者的方法，所述方法包括组合患者的血浆样品; ii）识别诱导结合位点上形成的诱导结合位点的可检测单克隆抗体 GP IIb / IIIa受体与纤维蛋白原受体拮抗剂与GP IIb / IIIa受体结合后，和ii）GP IIb / IIIa受体：GP IIb / III受体拮抗剂复合物，以及在血浆存在下确定可检测单克隆抗体与复合物的缔合。

10. 发明授权

US6063584A Anticoagulant test 失效
标题翻译：抗凝血试验
公开(公告)号：US6063584A
公开(公告)日：2000-05-16
申请号：US975312
申请日：1997-11-21
申请人： Bohumil Bednar , Robert J. Gould
发明人： Bohumil Bednar , Robert J. Gould
IPC分类号： G01N33/566 , G01N33/86
CPC分类号： G01N33/566 , G01N33/86
摘要： The present invention is a method for identifying a patient at risk to developing fibrinogen receptor antagonist-induced thrombocytopenia which comprises incubating patient plasma with a GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist complex to form a GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody complex, incubating the GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody complex with a secondary anti-human detectable antibody to form a GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody:secondary anti-human detectable antibody complex, and detecting the presence of the secondary anti-human detectable antibody in the GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody:secondary anti-human detectable antibody complex.
摘要翻译：本发明是用于鉴定处于发展纤维蛋白原受体拮抗剂诱发的血小板减少症的风险的患者的方法，其包括将患者血浆与GPIIb / IIIa受体：GPIIb / IIIa受体拮抗剂复合物孵育以形成GPIIb / IIIa受体：GPIIb / IIIa受体拮抗剂：血浆抗体复合物，培养GPIIb / IIIa受体：GPIIb / IIIa受体拮抗剂：血浆抗体复合物与第二抗人可检测抗体形成GPIIb / IIIa受体：GPIIb / IIIa受体拮抗剂：血浆抗体：人类可检测的抗体复合物，并检测GPIIb / IIIa受体中二级抗人可检测抗体的存在：GPIIb / IIIa受体拮抗剂：血浆抗体：第二抗人可检测抗体复合物。

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