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1. 发明申请

WO2008018084A3 PEPTIDES DERIVED FROM PLASMINOGEN ACTIVATOR INHIBITOR FOR PREVENTING NEURONAL DAMAGE 审中-公开
标题翻译：从PLASMINOGEN激活剂抑制剂衍生的预防神经损伤的肽
公开(公告)号：WO2008018084A3
公开(公告)日：2009-05-07
申请号：PCT/IL2007001007
申请日：2007-08-12
申请人： THROMBOTECH LTD , UNIV PENNSYLVANIA , HIGAZI ABD AL-ROOF , CINES DOUGLAS B
发明人： HIGAZI ABD AL-ROOF , CINES DOUGLAS B
IPC分类号： A61K38/00
CPC分类号： A61K38/08
摘要： The present invention relates to therapeutic uses of peptides comprising six amino acid residues derived from amino acids 350-355 of human plasminogen activator inhibitor 1 (PAI-1) for preventing neuronal damage due particularly to hypoxic or thromboembolic stroke and brain injury.
摘要翻译：本发明涉及包含衍生自人纤溶酶原激活物抑制剂1（PAI-1）的氨基酸350-355的六个氨基酸残基的肽用于预防特别是缺氧或血栓栓塞性卒中和脑损伤的神经元损伤的肽的治疗用途。

2. 发明申请

WO0197752A3 COMPOSITIONS COMPRISING UROKINASE FOR MODULATING MUSCLE CONTRACTILITY AND ANGIOGENISIS 审中-公开
标题翻译：包含用于调节肌肉收缩和血管生成的尿激酶的组合物
公开(公告)号：WO0197752A3
公开(公告)日：2002-06-27
申请号：PCT/US0118976
申请日：2001-06-13
申请人： UNIV PENNSYLVANIA , CINES DOUGLAS B , HIGAZI ABD AL-ROOF
发明人： CINES DOUGLAS B , HIGAZI ABD AL-ROOF
IPC分类号： A61K38/00 , A61K38/49 , C12N9/72 , A61K38/16 , A61K38/43 , C07H21/04 , C07K14/00 , C12Q1/37
CPC分类号： A61K38/49 , C12N9/6462 , C12Y304/21073 , A61K2300/00
摘要： The present invention relates to compositions and methods comprising one or more domains of urokinase-type plasminogen activator (uPA) in an amount effective to modulate one or more of the contractility and angiogenic activity of a mammalian muscle or endothelial cell or tissue for use in the treatment of a disease or condition having as a symptom thereof one or more of abnormal muscle cell or tissue contractility and abnormal angiogenic activity. The one or more domains of uPA can be present in the inventive compositions and methods either as part of the full uPA molecule in either single chain or two chain form (scuPA or tcuPA), or as an isolated polypeptide, or a fragment of the uPA molecule (e.g., the amino terminal fragment "ATF"), or a deletion mutant of the uPA molecule. The inventive methods comprise administering to a mammal afflicted with such a disease or condition the inventive composition, and modulating one or more of the contractility and the angiogenic activity of the muscle or endothelial cell or tissue, thereby treating the disease or condition. Kits for treating such diseases are also included.
摘要翻译：本发明涉及组合物和方法，其包含一种或多种尿激酶型纤溶酶原激活物结构域（uPA），其量有效调节哺乳动物肌肉或内皮细胞或组织的一种或多种收缩性和血管生成活性，以用于治疗作为其症状的一种或多种异常肌细胞或组织收缩力和异常血管生成活性的疾病或病症。 uPA的一个或多个结构域可以存在于本发明的组合物和方法中，作为单链或两链形式（scuPA或tcuPA）中的完整uPA分子的一部分，或作为分离的多肽或uPA的片段分子（例如，氨基末端片段“ATF”）或uPA分子的缺失突变体。本发明的方法包括给患有这种疾病或疾病的哺乳动物施用本发明的组合物，并调节肌肉或内皮细胞或组织的一种或多种收缩性和血管生成活性，从而治疗疾病或病症。也包括用于治疗这些疾病的药盒。

3. 发明申请

WO2008039206A3 FUSION PROTEINS FOR INHIBITION AND DISSOLUTION OF COAGULATION 审中-公开
标题翻译：用于抑制和溶解凝血酶的融合蛋白
公开(公告)号：WO2008039206A3
公开(公告)日：2008-09-18
申请号：PCT/US2006038989
申请日：2006-10-05
申请人： UNIV PENNSYLVANIA , GOTTSTEIN CLAUDIA , MUZYKANTOV VLADIMIR R , DING BI-SEN , CINES DOUGLAS B
发明人： GOTTSTEIN CLAUDIA , MUZYKANTOV VLADIMIR R , DING BI-SEN , CINES DOUGLAS B
IPC分类号： A61K39/00
CPC分类号： C07K16/2803 , A61K2039/505 , C07K2317/622 , C07K2319/20
摘要： Fusion proteins containing a ligand which specifically binds to a selected vascular bed linked to an anti- thrombotic molecule are provided. Also provided are methods for use of these fusion proteins to prevent coagulation, to dissolve blood clots and to protect against the risk of iatrogenic side effects including those arising from cancer therapy and specific vascular occluding agents.
摘要翻译：提供了含有特异性结合至与抗血栓形成分子连接的选定血管床的配体的融合蛋白质。还提供了使用这些融合蛋白以防止凝血，溶解血块和防止医源性副作用（包括由癌症治疗和特异性血管闭塞剂引起的副作用）的风险的方法。

4. 发明申请

WO2013165969A3 METHODS AND KITS FOR DIAGNOSING HEPARIN-INDUCED THROMBOCYTOPENIA 审中-公开
标题翻译：用于诊断HEPARIN诱导的血栓形成的方法和试剂盒
公开(公告)号：WO2013165969A3
公开(公告)日：2014-01-23
申请号：PCT/US2013038795
申请日：2013-04-30
申请人： UNIV PENNSYLVANIA
发明人： CINES DOUGLAS B , CUKER ADAM , SACHAIS BRUCE
IPC分类号： C07K16/00 , C07K16/34 , G01N33/50
CPC分类号： G01N33/6854 , G01N33/6893 , G01N2333/522 , G01N2400/40 , G01N2800/222
摘要： Provided herein are methods for diagnosing heparin-induced thrombocytopenia (HIT) in a subject. The methods comprise (a) contacting a PF4-heparin complex with a biological sample from the subject; (b) contacting the composition of part (a) with an HIT-like antibody; and (c) measuring the amount of bound HIT-like antibody. In one embodiment, a significant decrease in the amount of bound HIT-like antibody in the composition of part (b) as compared to a control level is indicative of a diagnosis of HIT in the subject. Also provided are assay kits for performing the methods of the invention.
摘要翻译：本文提供了用于诊断受试者中肝素诱导的血小板减少症（HIT）的方法。方法包括（a）使PF4-肝素复合物与来自受试者的生物样品接触; （b）将部分（a）的组合物与HIT样抗体接触; 和（c）测量结合的HIT样抗体的量。在一个实施方案中，与对照水平相比，部分（b）的组合物中结合的HIT样抗体的量的显着降低指示受试者中HIT的诊断。还提供了用于实施本发明方法的测定试剂盒。

5. 发明申请

WO2007041573A3 CRYSTAL STRUCTURE OF HUMAN UROKINASE PLASMINOGEN ACTIVATOR AMINO TERMINAL FRAGMENT BOUND TO ITS RECEPTOR 审中-公开
标题翻译：人尿激酶型纤溶酶原激活物氨基末端片段与其受体结合的晶体结构
公开(公告)号：WO2007041573A3
公开(公告)日：2007-10-04
申请号：PCT/US2006038608
申请日：2006-10-03
申请人： ATTENUON LLC , BETH ISRAEL HOSPITAL , UNIV PENNSYLVANIA
发明人： MAZAR ANDREW P , HUANG MINGDONG , HUAI QING , PARRY GRAHAM C , CINES DOUGLAS B
IPC分类号： C07K14/745 , C07K16/40
CPC分类号： C07K16/40 , C07K14/705 , C07K2299/00 , C12N9/6462 , C12Y304/21073
摘要： Urokinase-type plasminogen activator (uPA) binds its cellular receptor (uPAR) with high affinity, thus localizing the generation of plasmin from plasminogen on the surface of a variety of cells. Disclosed herein is the structure of suPAR (uPAR 1-277 ) complexed with the amino terminal fragment (ATF) of uPA (uPA 1-143 ) at a resolution of 1.9ú by X-ray crystallography. Three consecutive domains of uPAR (Dl, D2 and D3) form the shape of a thick-walled teacup with a cone shape cavity in the middle, which has a wide opening (25ú) and large depth (14ú). uPA 1-143 inserts into the cavity of uPAR and forms a large interface. The structure provides the basis for high affinity binding between uPA and uPAR and suggests the Dl and D2 domain of uPAR and the GFD domain of uPA (uPA 7-43 ) are primarily responsible for uPA-uPAR binding. This structure presents the first high resolution view of uPA-uPAR interaction, and provides, among other things, a new platform for designing uPA-uPAR inhibitors/antagonists.
摘要翻译：尿激酶型纤溶酶原激活剂（uPA）以高亲和力结合其细胞受体（uPAR），从而使来自各种细胞表面的纤溶酶原的纤溶酶产生定位。本文公开了分辨率为1.9μ的与uPA（uPA1-143）的氨基末端片段（ATF）复合的suPAR（uPAR1-277）的结构通过X射线晶体学。 uPAR的三个连续区域（D1，D2和D3）形成中间具有锥形腔的厚壁茶杯的形状，其具有宽开口（25°）和大深度（14°）。 uPA <1-143 插入uPAR的空腔并形成一个大的界面。该结构为uPA和uPAR之间的高亲和力结合提供了基础，并且表明uPAR的D1和D2结构域和uPA的GFD结构域（uPA 7-43）主要负责uPA-uPAR结合。该结构呈现了uPA-uPAR相互作用的第一个高分辨率视图，并且提供了设计uPA-uPAR抑制剂/拮抗剂的新平台等等。

6. 发明申请

WO2013142330A1 METHODS OF IDENTIFYING HIT-ANTIBODIES AND PF4 ANTAGONISTS AND CELL LINES FOR USE THEREIN 审中-公开
标题翻译：识别HIT抗体和PF4拮抗剂和细胞系的方法
公开(公告)号：WO2013142330A1
公开(公告)日：2013-09-26
申请号：PCT/US2013032100
申请日：2013-03-15
申请人： UNIV PENNSYLVANIA
发明人： WATSON STEVE P , SACHAIS BRUCE , CINES DOUGLAS B
IPC分类号： G01N33/53
CPC分类号： G01N33/5008 , G01N33/5044 , G01N33/6854 , G01N33/6893 , G01N2800/222
摘要： Methods and cells or cell lines for identifying antibodies or fragments thereof that activate heparin-induced thrombocytopenia (HIT) are described. The methods comprise contacting a hematopoietic cell or cell line that comprises, in operative association, the platelet receptor FcyRIIA under the control of a suitable promoter, and a reporter construct comprising a reporter gene under the control of a promoter and transcription factor, which transcription factor is regulated downstream of the signaling cascade of activated FcyRIIA, with a test sample from a mammalian subject; a platelet factor 4 (PF4), a wild-type or variant of PF4 or a fragment thereof; and heparin; and detecting or measuring the level of reporter gene expression.
摘要翻译：描述了用于鉴定激活肝素诱导的血小板减少症（HIT）的抗体或其片段的方法和细胞或细胞系。所述方法包括使造血细胞或细胞系接触，所述造血细胞或细胞系在合适的关联下包含在合适的启动子控制下的血小板受体FcyRIIA，以及包含在启动子和转录因子控制下的报告基因的报道构建体，该转录因子在活化的FcyRIIA的信号级联的下游被调节，来自哺乳动物受试者的测试样品; 血小板因子4（PF4），PF4的野生型或变体或其片段; 和肝素; 并检测或测定报告基因表达水平。

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