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1. 发明申请

WO2010045518A1 COMPOSITIONS CONTAINING THROMBOMODULIN DOMAINS AND USES THEREOF 审中-公开
标题翻译：含有酪氨酸蛋白酶域的组合物及其用途
公开(公告)号：WO2010045518A1
公开(公告)日：2010-04-22
申请号：PCT/US2009/060938
申请日：2009-10-16
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , MUZYKANTOV, Vladimir, R. , DING, Bi-Sen , CINES, Douglas, B. , GOTTSTEIN, Claudia , ALBELDA, Steven, M.
发明人： MUZYKANTOV, Vladimir, R. , DING, Bi-Sen , CINES, Douglas, B. , GOTTSTEIN, Claudia , ALBELDA, Steven, M.
IPC分类号： A61K35/14 , A61P7/02 , C07K16/46
CPC分类号： C07K16/2803 , A61K38/366 , A61K2039/505 , C07K14/7455 , C07K2317/622 , C07K2319/00 , C07K2319/33 , C07K2319/74
摘要： Compositions are provided comprising a thrombomodulin domain linked to a targeting moiety that binds to a determinant on the surface of a target endothelial cell or red blood cell, wherein the thrombomodulin domain may be the extracellular domain, the N-terminal lectin-like domain, or an epidermal growth factor (EGF)-like domain. The targeting moiety may be a single chain antigen-binding domain (scFv), and the targeting moiety and thrombomodulin domain of the composition may be linked as a continuous polypeptide chain. Methods of delivery and use of a composition described herein are provided, as well as methods of treating or preventing thrombosis, inflammation, tissue ischemia, sepsis, acute lung injury (ALI), acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease is provided.
摘要翻译：提供的组合物包含与靶向部分结合的血栓调节蛋白结构域，所述靶向部分与靶内皮细胞或红细胞表面上的决定簇结合，其中所述血栓调节蛋白结构域可以是细胞外结构域，N末端凝集素样结构域，或表皮生长因子（EGF）样结构域。靶向部分可以是单链抗原结合结构域（scFv），并且组合物的靶向部分和血栓调节蛋白结构域可以作为连续的多肽链连接。提供本文所述的组合物的递送和使用方法，以及治疗或预防血栓形成，炎症，组织缺血，败血症，急性肺损伤（ALI），急性心肌梗塞（AMI），缺血性卒中，脑血管疾病，提供肺栓塞或缺血性外周血管疾病。

2. 发明申请

WO2008039206A2 FUSION PROTEINS FOR INHIBITION AND DISSOLUTION OF COAGULATION 审中-公开
标题翻译：融合蛋白用于凝血抑制和溶解
公开(公告)号：WO2008039206A2
公开(公告)日：2008-04-03
申请号：PCT/US2006/038989
申请日：2006-10-05
申请人： THE TRUSTEES OF THE UNIVERSITY OF 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： A61K39/395
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与抗血栓形成分子连接的选定血管床的配体的融合蛋白。还提供了使用这些融合蛋白来防止凝血，溶解血凝块和防止医源性副作用的风险的方法，所述医源性副作用包括由癌症治疗和特定血管闭塞剂引起的那些副作用。

3. 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。

4. 发明申请

WO2008018084A2 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：WO2008018084A2
公开(公告)日：2008-02-14
申请号：PCT/IL2007/001007
申请日：2007-08-12
申请人： THROMBOTECH LTD. , THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , HIGAZI, Abd Al-Roof , CINES, Douglas, B.
发明人： HIGAZI, Abd Al-Roof , CINES, Douglas, B.
IPC分类号： A61K38/08
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。

5. 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。

6. 发明申请

WO2016073747A1 ATOMIC DESCRIPTION OF IMMUNE COMPLEX THAT CAUSES HEPARIN-INDUCED THROMBOCYTOPENIA 审中-公开
标题翻译：导致HEPARIN诱导的血栓形成的免疫复合物的原理描述
公开(公告)号：WO2016073747A1
公开(公告)日：2016-05-12
申请号：PCT/US2015/059283
申请日：2015-11-05
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , GREENE, Mark, I. , CINES, Douglas, B. , CAI, Zheng , ZHU, Zhiqiang
发明人： GREENE, Mark, I. , CINES, Douglas, B. , CAI, Zheng , ZHU, Zhiqiang
IPC分类号： G01N33/577 , G01N33/53 , C07K16/18
CPC分类号： G01N33/6863 , A61K38/195 , A61K39/3955 , A61K2039/505 , C07K14/522 , C07K16/24 , G01N33/86 , G01N2333/522 , G01N2400/40 , G01N2800/222 , G01N2800/50 , G01N2800/52
摘要： The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-Ll, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants. The present invention also provides a mutant protein which has the same amino acid sequence of a wild type PF4 monomer except that (i) at least one amino acid of the wild type PF4 monomer has been deleted, (ii) at least one amino acid of the wild type PF4 monomer has been replaced by another amino acid, or (iii) a combination of such changes has been made. The present invention also provides methods of treating or reducing the likelihood of HIT, treating angiogenesis, treating abnormal cell growth, or affecting coagulation pathologies that lead to thrombus formation, by administering such mutant proteins to a patient.
摘要翻译：本发明提供包含（a）人源化轻链的人源化抗体或抗体片段，其包含1）互补决定区（CDR）-L1，其序列与SEQ ID NO：3的序列相同; 2）CDR-L2，其序列与SEQ ID NO：4的序列相同; 和3）CDR-L3，其序列与SEQ ID NO：5的序列相同，和（b）人源化重链，其包含1）CDR-H1，其序列与SEQ ID NO： NO：6; 2）CDR-H2，其序列与SEQ ID NO：7的序列相同; 和3）CDR-H3，其序列与SEQ ID NO：8的序列相同，以及治疗，诊断和监测HIT进展的方法。本发明还提供了评估阴离子抗凝剂的抗原性和引起HIT的能力的方法。本发明还提供了具有与野生型PF4单体相同的氨基酸序列的突变蛋白，除了（i）野生型PF4单体的至少一个氨基酸已经缺失，（ii）至少一个氨基酸野生型PF4单体已被另一种氨基酸取代，或（iii）已经进行了这种变化的组合。本发明还提供了通过向患者施用这种突变蛋白来治疗或降低HIT的可能性，治疗血管发生，治疗异常细胞生长或影响导致血栓形成的凝血病理学的方法。

7. 发明申请

WO2009086552A1 TARGETING RECOMBINANT THERAPEUTICS TO CIRCULATING RED BLOOD CELLS 审中-公开
标题翻译：指导重组治疗方法循环红细胞
公开(公告)号：WO2009086552A1
公开(公告)日：2009-07-09
申请号：PCT/US2008/088632
申请日：2008-12-31
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , MUZYKANTOV, Vladimir, R. , ZAITSEV, Sergei, V. , DING, Bi-sen , CINES, Douglas, B.
发明人： MUZYKANTOV, Vladimir, R. , ZAITSEV, Sergei, V. , DING, Bi-sen , CINES, Douglas, B.
IPC分类号： A61K39/00
CPC分类号： C07K16/18 , A61K2039/505 , C07K16/28 , C07K2317/622 , C07K2319/01 , C07K2319/50
摘要： Fusion proteins comprising an single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.
摘要翻译：提供了包含与抗血栓形成剂，抗炎剂或其前体药物连接的单克隆抗体的单链抗原结合结构域（scFv）的融合蛋白，其中多肽与结合位点（抗原）在红细胞的表面上以每个红细胞大于5,000拷贝的密度表达。包含这些融合蛋白的药物组合物，以及通过这些融合蛋白的递送将抗血栓形成剂递送到红细胞表面的方法，以及治疗或预防血栓形成，组织缺血，急性心肌梗塞（AMI），缺血性还提供了通过施用融合蛋白或包含其的组合物的中风，脑血管疾病，肺栓塞或缺血性外周血管疾病。

8. 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。

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