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31. 发明申请

WO0234776A3 EPITOPES OF PAI-1 审中-公开
标题翻译： PAI-1的抗体
公开(公告)号：WO0234776A3
公开(公告)日：2004-01-08
申请号：PCT/BE0100186
申请日：2001-10-25
申请人： LEUVEN K U RES & DEV , DECLERCK PAUL , STASSEN JEAN-MARIE , BIJNENS ANN-PASCAL , GILS ANN , NGO THU HOA
发明人： DECLERCK PAUL , STASSEN JEAN-MARIE , BIJNENS ANN-PASCAL , GILS ANN , NGO THU HOA
IPC分类号： A61K38/00 , C07K14/81 , C12N15/15 , A61K39/395 , C07K16/38 , G01N33/53
CPC分类号： C07K14/8132 , A61K38/00
摘要： The invention belongs to the field of cardiovascular and thromboembolic diseases or cancer and related diseases. The invention relates to proteins, peptides comprising specified epitopes of plasminogen activator inhibitor type-1 (PAI-1) and nucleic acids encoding said proteins or peptides. The invention further relates to methods of screening for substances capable of inhibiting said PAI-1, substances identifiable with said method and pharmaceutical compositions comprising said substances.
摘要翻译：本发明属于心血管和血栓栓塞性疾病或癌症及相关疾病领域。本发明涉及包含纤溶酶原激活物抑制剂1型（PAI-1）的特定表位的蛋白质和编码所述蛋白质或肽的核酸的肽。本发明还涉及筛选能够抑制所述PAI-1的物质的方法，所述方法可鉴定的物质和包含所述物质的药物组合物。

32. 发明申请

WO2003071267A1 THERAPEUTIC METHODS EMPLOYING PAI-1 INHIBITORS AND TRANSGENIC NON-HUMAN ANIMAL FOR SCREENING CANDIDATE PAI-1 INHIBITORS 审中-公开
标题翻译：使用PAI-1抑制剂和转基因非人动物筛选候选PAI-1抑制剂的治疗方法
公开(公告)号：WO2003071267A1
公开(公告)日：2003-08-28
申请号：PCT/US2003/005008
申请日：2003-02-19
申请人： VANDERBILT UNIVERSITY , DECLERCK, Paul, J. , VAUGHAN, Douglas, E. , EREN, Mesut
发明人： DECLERCK, Paul, J. , VAUGHAN, Douglas, E. , EREN, Mesut
IPC分类号： G01N33/00
CPC分类号： C12N15/873 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0312 , C07K14/8132 , C12N15/8509 , C12Q1/56 , G01N33/566 , G01N33/68 , G01N33/6893 , G01N33/6896 , G01N33/86 , G01N2333/8132 , G01N2500/00
摘要： A method of treating a warm-blooded vertebrate animal having a medical condition in need of treatment with a composition that exhibits PAI-1 inhibition activity is disclosed. The method includes the steps of administering a treatment effective amount of the composition to a warmblooded vertebrate animal having a medical condition selected from the group consisting of alopecia, undesired weight loss, Alzheimer's Disease, systemic amyloidosis, myelofibrosis, male pattern baldness, glomerulosclerosis, and combinations thereof; and observing an improvement in the medical condition in the warm-blooded vertebrate animal having the medical condition. A method of testing a candidate composition for PAI-1 inhibition activity is also disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer overexpression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful is such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.
摘要翻译：公开了一种治疗需要用表现出PAI-1抑制活性的组合物治疗的具有医学病症的温血脊椎动物的方法。该方法包括以下步骤：将治疗有效量的组合物施用于具有选自脱发，不希望的体重减轻，阿尔茨海默病，全身淀粉样变性，骨髓纤维化，男性型秃发，肾小球硬化和其组合; 并观察具有医疗状况的温血脊椎动物的医疗状况的改善。还公开了测试候选组合物用于PAI-1抑制活性的方法。该方法包括以下步骤：获得在其基因组中掺入了编码生物活性PAI-1多肽的PAI-1基因的转基因非人类温血脊椎动物，所述PAI-1基因以有效的拷贝数存在于基因组中以在PAI-1多肽的转基因非人动物中赋予过表达; 将所述组合物施用于所述转基因非人动物; 并观察转基因非人动物以测定表达PAI-1活性抑制的转基因非人动物的变化。还公开了一种有用的转基因非人动物，编码可用于制备转基因非人动物的生物活性PAI-1多肽的PAI-1转基因构建体也是公开的。

33. 发明申请

WO03059946A2 GENETIC POLYMORPHISMS PREDICTING CARDIOVASCULAR DISEASE AND MEDICATION EFFICACY 审中-公开
标题翻译：遗传多态性预测心血管疾病和药物效能
公开(公告)号：WO03059946A2
公开(公告)日：2003-07-24
申请号：PCT/EP0300161
申请日：2003-01-10
申请人： BAYER AG , STROPP UDO , SCHWERS STEPHAN , KALLABIS HARALD , SCHMITZ GERD
发明人： STROPP UDO , SCHWERS STEPHAN , KALLABIS HARALD , SCHMITZ GERD
IPC分类号： A61K38/00 , A61K38/17 , C07K14/47 , C07K14/49 , C07K14/52 , C07K14/535 , C07K14/775 , C07K14/81 , C12Q1/68
CPC分类号： C12Q1/6883 , A61K38/00 , C07K14/4702 , C07K14/49 , C07K14/52 , C07K14/535 , C07K14/775 , C07K14/8132 , C12Q2600/156
摘要： The present invention relates to isolated polynucleotides encoding a cardiovascular associated CA gene polypeptide useful in methods to identify therapeutic agents and useful for preparation of a medicament to treat cardiovascular disease, the polynucleotide is selected from the group comprising:SEQ ID 1, 2, 3, 4, 5, 6 with allelic variation as indicated in the sequences section contained in a functional surrounding like full length cDNA for CA gene polypeptide and with or without the CA gene promoter sequence.The invention also provides diagnostic methods and kits including antibodies determining whether a human subject is at risk for a cardiovascular disease. The invention provides further polymorphic sequences and other genes.
摘要翻译：本发明涉及编码心血管相关CA基因多肽的分离的多核苷酸，其用于鉴定治疗剂并可用于制备治疗心血管疾病的药物的方法中，所述多核苷酸选自SEQ ID No.1,2,3， 4,5,6等位基因变异，如包含在功能性周围的序列部分中所示，如CA基因多肽的全长cDNA和具有或不具有CA基因启动子序列。本发明还提供诊断方法和试剂盒，其包括确定是否人类受试者面临心血管疾病的风险。本发明提供了更多的多态序列和其他基因。

34. 发明申请

WO03053921A2 MUTANT PROTEINASE INHIBITORS AND USES THEREOF 审中-公开
标题翻译：突变型蛋白酶抑制剂及其用途
公开(公告)号：WO03053921A2
公开(公告)日：2003-07-03
申请号：PCT/US0222822
申请日：2002-07-18
申请人： AMERICAN NAT RED CROSS , LAWRENCE DANIEL A , GORLATOVA NATALIA , CRANDALL DAVID L
发明人： LAWRENCE DANIEL A , GORLATOVA NATALIA , CRANDALL DAVID L
IPC分类号： G01N33/50 , A61K45/00 , A61P43/00 , C07K14/81 , C07K16/38 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N15/09 , C12P21/02 , C12Q1/37 , G01N33/15 , G01N33/53 , G01N33/566 , C07D
CPC分类号： C07K14/8121 , C07K14/81 , C07K14/8132 , C07K16/38 , C12Q1/37 , G01N2333/81 , G01N2500/04
摘要： A library of mutants of metastable proteins, such as proteinase inhibitors, can be screened for the specific loss of a wild-type capability to bind an antibody, yielding valuable drug-design information which otherwise is unavailable. By this approach, for example, a mutant proteinase inhibitor can be obtained that has the amino acid sequence of a wild-type protein, or an active fragment therof, save for the presence of one or more mutations in at least one epitope, thereby altering interaction of the mutant with an anti-proteinase inhibitor antibody.
摘要翻译：可以筛选亚稳态蛋白质突变体的文库，例如蛋白酶抑制剂，以便特异性丧失结合抗体的野生型能力，产生否则不可用的有价值的药物设计信息。通过该方法，例如，可以获得具有野生型蛋白质的氨基酸序列或活性片段的突变蛋白酶抑制剂，除了在至少一个表位中存在一个或多个突变，从而改变突变体与抗蛋白酶抑制剂抗体的相互作用。

35. 发明申请

WO2002060952A1 SERPIN VARIANTS AND USES THEREOF 审中-公开
标题翻译： SERPIN VARIANTS及其用途
公开(公告)号：WO2002060952A1
公开(公告)日：2002-08-08
申请号：PCT/GB2002/000405
申请日：2002-01-30
申请人： CAMBRIDGE UNIVERSITY TECHNICAL SERVICES LIMITED , CARRELL, Wayne, Robin , HUNTINGTON, James, Andrew , ZHOU, Aiwu
发明人： CARRELL, Wayne, Robin , HUNTINGTON, James, Andrew , ZHOU, Aiwu
IPC分类号： C07K14/81
CPC分类号： C07K14/8121 , A61K38/00 , C07K14/8125 , C07K14/8132
摘要： The present invention relates to generation and use of protein variants of serpins (SerineProteaseInhibitors). Serpins bind and inhibit serine proteases and both serpins and serine proteases are highly conserved structurally. The amino acid sequences of various different serpins may be altered, in each case creating a serpin variant, with the effect of generating a protein that forms a complex with target serine protease then releases the protease over time - intact and active. This contrasts with the natural activity of serpins which is to bind the target serine protease and irreversibly inhibit it, destroying activity and ultimately targeting the protease for destruction. Polypeptides, methods and means related to these serpin variants are provided.
摘要翻译：本发明涉及丝氨酸蛋白酶（SerineProteaseInhibitors）的蛋白质变体的产生和应用。丝氨酸蛋白酶结合并抑制丝氨酸蛋白酶，丝氨酸蛋白酶和丝氨酸蛋白酶在结构上是高度保守的。可以改变各种不同丝氨酸蛋白酶的氨基酸序列，在每种情况下产生丝氨酸蛋白酶变体，其产生与靶丝氨酸蛋白酶形成复合物的蛋白质，随后随着时间的推移释放蛋白酶 - 完整和活性。这与丝氨酸蛋白酶的自然活性形成对比，其是与靶丝氨酸蛋白酶结合并且不可逆地抑制它，破坏活性并最终靶向蛋白酶进行破坏。提供了与这些丝氨酸蛋白酶抑制剂变体相关的多肽，方法和方法。

36. 发明申请

WO02034776A2 EPITOPES OF PAI-1 审中-公开
标题翻译： PAI-1的抗体
公开(公告)号：WO02034776A2
公开(公告)日：2002-05-02
申请号：PCT/BE2001/000186
申请日：2001-10-25
IPC分类号： A61K38/00 , C07K14/81 , C12N15/15 , C07K14/47
CPC分类号： C07K14/8132 , A61K38/00
摘要： The invention belongs to the field of cardiovascular and thromboembolic diseases or cancer and related diseases. The invention relates to proteins, peptides comprising specified epitopes of plasminogen activator inhibitor type-1 (PAI-1) and nucleic acids encoding said proteins or peptides. The invention further relates to methods of screening for substances capable of inhibiting said PAI-1, substances identifiable with said method and pharmaceutical compositions comprising said substances.
摘要翻译：本发明属于心血管和血栓栓塞性疾病或癌症及相关疾病领域。本发明涉及包含纤溶酶原激活物抑制剂1型（PAI-1）的特定表位的蛋白质和编码所述蛋白质或肽的核酸的肽。本发明还涉及筛选能够抑制所述PAI-1的物质的方法，所述方法可鉴定的物质和包含所述物质的药物组合物。

37. 发明申请

WO01070962A1 A NOVEL POLYPEPTIDE, A HUMAN PLASMINOGEN ACTIVATOR INHIBITOR 10 AND THE POLYNUCLEOTIDE ENCODING THE POLYPEPTIDE 审中-公开
公开(公告)号：WO01070962A1
公开(公告)日：2001-09-27
申请号：PCT/CN2001/000373
申请日：2001-03-19
IPC分类号： C07K14/81 , C12N15/12 , A61K38/17 , C07K14/435
CPC分类号： C07K14/8132
摘要： The present invention discloses a novel polypeptide, a human plasminogen activator inhibitor 10, the polynucleotide encoding the polypeptide and the method for producing the plypetide by DNA recombinant technology. The invention also discloses the uses of the polypeptide in methods for treating various diseases, such as hemorrhagic illness, thrombopoies, cerebral, infarction, myocardial infarction, various tumour, inflammation, inflammatory repair abnormality relative illness, embryonic development disorder, hemopathy, HIV infection, etc. The invention also discloses the agonists against the polyptide and the therapeutic action tereof. The invention also discloses the uses of the polynucleotide encoding the novel human plasminogen activator inhibitor 10.

38. 发明申请

WO1997039028A1 MUTANT PLASMINOGEN ACTIVATOR-INHIBITOR TYPE 1 (PAI-1) AND USES THEREOF 审中-公开
标题翻译：突变型PLASMINOGEN激活剂抑制剂1型（PAI-1）及其用途
公开(公告)号：WO1997039028A1
公开(公告)日：1997-10-23
申请号：PCT/US1997006071
申请日：1997-04-11
申请人： AMERICAN NATIONAL RED CROSS
发明人： AMERICAN NATIONAL RED CROSS , LAWRENCE, Daniel, A. , STEFANSSON, Steingrimur, P.
IPC分类号： C07K14/00
CPC分类号： C07K16/28 , A61K38/00 , C07K14/8132 , C07K2317/77
摘要： Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells. Such conditions include atherosclerosis, post angioplasty restenosis, fibrosis associated with chronic inflammation or chemotherapy, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. Also disclosed are peptides of such mutant proteins, mutant-specific antibodies, nucleic acid molecules, particularly DNA, encoding the mutant protein and host cells transformed by such nucleic acids.
摘要翻译：描述了人PAI-1蛋白的突变体，其是嗜中性粒细胞弹性蛋白酶抑制剂或玻连蛋白（Vn）依赖性细胞迁移的抑制剂。这些突变体优选在PAI-1的反应中心环中，特别是成熟蛋白的位置331和346处包含一个或两个氨基酸取代。这些突变体在抵抗对Vn具有高亲和力的弹性蛋白酶的失活或两种性质方面是显着的。这些作为药物组合物的突变蛋白质用于抑制受试者中的弹性蛋白酶，从而治疗与弹性蛋白酶活性相关的许多障碍，特别是肺气肿，ARDS，炎症性肺损伤和囊性纤维化。与Vn相互作用的突变体用于抑制受试者中的细胞迁移，从而治疗与不期望的细胞迁移和增殖相关的疾病或病症，特别是平滑肌细胞的增殖。这些病症包括动脉粥样硬化，血管成形术后再狭窄，与慢性炎症或化学疗法相关的纤维化，肿瘤浸润和转移以及血管发生是致病性的病症。还公开了这样的突变蛋白质，突变体特异性抗体，核酸分子，特别是DNA，编码由这种核酸转化的突变蛋白质和宿主细胞的肽。

39. 发明申请

WO1996021416A2 METHODS AND COMPOSITIONS FOR TREATMENT OF SOLID TUMORS IN VIVO 审中-公开
标题翻译：用于治疗体内实体肿瘤的方法和组合物
公开(公告)号：WO1996021416A2
公开(公告)日：1996-07-18
申请号：PCT/US1995016855
申请日：1995-12-22
申请人： CHIRON VIAGENE, INC.
发明人： CHIRON VIAGENE, INC. , BURROWS, Francis, J. , FONG, Timothy, C , POLO, John, M. , DUBENSKY, Thomas, W., Jr. , JOLLY, Douglas, J.
IPC分类号： A61K00/00
CPC分类号： C12N9/0069 , A61K38/00 , A61K48/00 , C07K14/57 , C07K14/705 , C07K14/745 , C07K14/8132 , C07K14/8146 , C12N9/1211 , C12N9/6491 , C12N2799/021 , C12N2799/027
摘要： The present invention provides compositions and methods for treatment of solid tumors with gene therapy utilizing recombinant viral vectors that express polypeptides which selectively initiate irreversible coagulation of blood in the tumor vasculature, inhibit tumor neovascularization, are capable of activating a non-toxic agent into a toxic agent within the tumor vascular wall causing destruction of the vascular bed and absorb or metabolize nutrients in the blood being supplied to the tumor. The production of these polypeptides by transduced cells in or adjacent to the blood vessels of the tumor result in the death of tumor cells.
摘要翻译：本发明提供了使用重组病毒载体的基因治疗用于治疗实体瘤的组合物和方法，所述重组病毒载体表达选择性地启动肿瘤脉管系统中的血液不可逆凝结，抑制肿瘤新生血管形成，能够将无毒物质活化成毒性的多肽肿瘤血管壁内的药剂导致血管床的破坏并吸收或代谢供应到肿瘤的血液中的营养物质。这些多肽通过在肿瘤血管中或邻近的转导细胞的产生导致肿瘤细胞的死亡。

40. 发明申请

WO1988001273A1 DIAGNOSTIC ASSAY FOR INHIBITOR OF TISSUE-TYPE AND UROKINASE-TYPE PLASMINOGEN ACTIVATORS, AND GENE CODING FOR THE INHIBITOR 审中-公开
标题翻译：用于组织型和尿激酶型PLASMINOGEN激活剂的抑制剂的诊断测定和抑制剂的基因编码
公开(公告)号：WO1988001273A1
公开(公告)日：1988-02-25
申请号：PCT/US1987002053
申请日：1987-08-19
申请人： SCRIPPS CLINIC AND RESEARCH FOUNDATION
发明人： SCRIPPS CLINIC AND RESEARCH FOUNDATION , LOSKUTOFF, David, J. , NY, Tor , SAWDEY, Michael
IPC分类号： C07H17/00
CPC分类号： G01N33/86 , C07K14/005 , C07K14/8132 , C07K2319/00 , C07K2319/02 , C07K2319/33 , C07K2319/61 , C12N15/81 , C12N15/85 , C12N2710/16622 , G01N2333/8132 , G01N2333/9723 , G01N2333/9726
摘要： A biological reagent and diagnostic system for the detection and quantitation of endothelial plasminogen activator inhibitor (PAI), as are substantially pure, recombinant human endothelial PAI, its biologically pure gene and a vector for cloning the gene and expressing a gene product.
摘要翻译：用于检测和定量内皮纤溶酶原激活物抑制剂（PAI）的生物试剂和诊断系统，基本上是纯的，重组人内皮PAI，其生物学纯基因和用于克隆基因并表达基因产物的载体。

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