利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

58 条记录 (耗时 0.033 秒)

    Protease Activated Receptor-1 (PAR1) Derived Cytoprotective Polypeptides and Related Methods
    12.
    发明授权
    Protease Activated Receptor-1 (PAR1) Derived Cytoprotective Polypeptides and Related Methods 有权

    公开(公告)号：US09605046B2

    公开(公告)日：2017-03-28

    申请号：US14356692

    申请日：2012-11-07

    申请人： THE SCRIPPS RESEARCH INSTITUTE ,  Laurent O. Mosnier ,  John H. Griffin

    发明人： Laurent O. Mosnier ,  John H. Griffin

    IPC分类号： A61K38/00 ,  A61P5/00 ,  C07K14/705 ,  A61K38/17

    CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K38/177

    摘要： The present invention provides novel PAR 1 derived cytoprotective oligopeptides or polypeptides which typically contain at least the first 4 N-terminal residues that are substantially identical to the corresponding N-terminal residues of Met1-Arg46 deleted human PAR 1 sequence. These cytoprotective oligopeptides or polypeptides are capable of activating PAR 1 and promoting PAR 1 cytoprotective signaling activities. The invention also provides engineered cells or transgenic non-human animals which harbor in their genome an altered PAR 1 gene that is resistant to cleavage at Arg41 and/or Arg46 residues. Additionally provided in the invention are methods of screening candidate compounds to identity additional cytoprotective compounds or cytoprotective proteases. The invention further provides therapeutic use or methods of employing a PAR 1 derived cytoprotective oligopeptide or polypeptide to treat conditions associated with tissue injuries or undesired apoptosis.

    ACTIVATED PROTEIN C VARIANTS WITH NORMAL CYTOPROTECTIVE ACTIVITY BUT REDUCED ANTICOAGULANT ACTIVITY
    13.
    发明申请
    ACTIVATED PROTEIN C VARIANTS WITH NORMAL CYTOPROTECTIVE ACTIVITY BUT REDUCED ANTICOAGULANT ACTIVITY 审中-公开
    具有正常CYTOPROTECTIVE活性的活化蛋白C变体，但降低抗血小板活性

    公开(公告)号：US20100028910A1

    公开(公告)日：2010-02-04

    申请号：US12391082

    申请日：2009-02-23

    申请人： John H. Griffin ,  Laurent O. Mosnier ,  Andrew J. Gale

    发明人： John H. Griffin ,  Laurent O. Mosnier ,  Andrew J. Gale

    IPC分类号： G01N33/53 ,  C12Q1/37 ,  C12N9/50

    CPC分类号： C12Y304/21069 ,  A61K38/4866 ,  C12N9/6464

    摘要： Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Two examples of such recombinant APC mutants are KKK191-193AAA-APC and RR229/230AA-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apopotosis. At risk patients include, for example, those suffering (severe) sepsis, ischemia/reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative diseases, or those undergoing organ transplantation or chemotherapy, among other conditions. Methods of screening for variants of recombinant protein C or APC that are useful in accordance with the invention are also provided.

    摘要翻译： 提供重组活化蛋白C（APC）或重组蛋白C（前体药物，能够转化为APC）的变体（突变体），其具有显着降低抗凝血活性，但保持正常水平的抗凋亡活性。 这些重组APC突变体的两个实例是KKK191-193AAA-APC和RR229 / 230AA-APC。 本发明的APC变体和前药具有细胞保护性（抗凋亡作用）的期望性质，同时具有显着降低的出血风险。 本发明还提供了使用本发明的APC变体或前药来治疗受益于APC的细胞保护活性而不受APC抗凝活性影响的受试者的方法。 这些受试者包括至少部分由凋亡引起的各种器官中血管或组织损伤风险的患者。 在危险中，患者包括例如患有（严重）败血症，缺血/再灌注损伤，缺血性卒中，急性心肌梗死，急性或慢性神经变性疾病或经历器官移植或化疗的患者等。 还提供了筛选根据本发明有用的重组蛋白C或APC的变体的方法。

    Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity
    19.
    发明授权
    Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity 有权
    具有正常细胞保护活性但具有降低的抗凝血活性的活化蛋白C变体

    公开(公告)号：US09192657B2

    公开(公告)日：2015-11-24

    申请号：US11589371

    申请日：2006-10-30

    申请人： John H. Griffin ,  Laurent O. Mosnier ,  Andrew J. Gale

    发明人： John H. Griffin ,  Laurent O. Mosnier ,  Andrew J. Gale

    IPC分类号： A61K38/48 ,  C12N9/64

    CPC分类号： A61K38/4866 ,  C12N9/6464 ,  C12Y304/21069

    摘要： Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Three examples of such recombinant APC mutants are KKK191-193AAA-APC, RR229/230AA-APC, and RR229/230AA plus KKK191-193AAA-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis. At risk patients include, for example, those suffering (severe) sepsis, ischemia/reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative diseases, or those undergoing organ transplantation or chemotherapy, among other conditions. Methods of screening for variants of recombinant protein C or APC that are useful in accordance with the invention are also provided.

    摘要翻译： 提供重组活化蛋白C（APC）或重组蛋白C（前体药物，能够转化为APC）的变体（突变体），其具有显着降低抗凝血活性，但保持正常水平的抗凋亡活性。 这些重组APC突变体的三个实例是KKK191-193AAA-APC，RR229 / 230AA-APC和RR229 / 230AA加上KKK191-193AAA-APC。 本发明的APC变体和前药具有细胞保护性（抗凋亡作用）的期望性质，同时具有显着降低的出血风险。 本发明还提供了使用本发明的APC变体或前药来治疗受益于APC的细胞保护活性而不受APC抗凝活性影响的受试者的方法。 这些受试者包括至少部分地通过细胞凋亡而导致各种器官的血管损伤或组织损伤风险的患者。 在危险中，患者包括例如患有（严重）败血症，缺血/再灌注损伤，缺血性卒中，急性心肌梗死，急性或慢性神经变性疾病或经历器官移植或化疗的患者等。 还提供了筛选根据本发明有用的重组蛋白C或APC的变体的方法。

    Protein S protects the nervous system from injury
    20.
    发明授权
    Protein S protects the nervous system from injury 失效
    蛋白S可保护神经系统免受伤害

    公开(公告)号：US07968515B2

    公开(公告)日：2011-06-28

    申请号：US10529748

    申请日：2003-09-30

    申请人： Berislav V. Zlokovic ,  John H. Griffin

    发明人： Berislav V. Zlokovic ,  John H. Griffin

    IPC分类号： A61K38/36

    CPC分类号： C07K14/8128 ,  A61K38/36 ,  G01N2500/10 ,  G01N2510/00

    摘要： Protein S is a significant neuroprotectant when administered after focal ischemic stroke and prevents hypoxic/re-oxygenation injury. Purified human plasma-derived or recombinant protein S improves motor neurological function after stroke, and reduced brain infarction and edema. Protein S also enhances post-ischemic reperfusion and reduced brain fibrin and neutrophil deposition. Cortical neurons are protected from hypoxia/re-oxygenation-induced apoptosis. Thus, protein S and variants thereof are prototypes of a class of agents for preventing injury of the nervous system. In particular, a disease or other pathological condition (e.g., stroke) may be treated with such agents having one or more protein S activities (e.g., anti-thrombotic and anti-inflammatory activities, direct cellular neuronal protective effects) although the latter activities are not be required.

    摘要翻译： 当局部缺血性中风后施用时，蛋白S是一种显着的神经保护剂，可预防缺氧/再氧合损伤。 纯化的人血浆来源或重组蛋白S改善中风后的运动神经功能，减少脑梗塞和水肿。 蛋白S还增强了缺血后再灌注并减少了脑纤维蛋白和嗜中性粒细胞沉积。 皮质神经元被保护免受缺氧/再氧合诱导的细胞凋亡。 因此，蛋白质S及其变体是用于预防神经系统损伤的一类试剂的原型。 特别地，可以用具有一种或多种蛋白S活性（例如，抗血栓形成和抗炎活性，直接细胞神经元保护作用）的药物治疗疾病或其它病理状况（例如中风），尽管后一种活性是 不需要。