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59 条记录 (耗时 0.033 秒)

    ACTIVATED PROTEIN C VARIANTS WITH NORMAL CYTOPROTECTIVE ACTIVITY BUT REDUCED ANTICOAGULANT ACTIVITY
    11.
    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。

    Protease Activated Receptor-1 (PAR1) Derived Cytoprotective Polypeptides and Related Methods
    18.
    发明申请
    Protease Activated Receptor-1 (PAR1) Derived Cytoprotective Polypeptides and Related Methods 审中-公开

    公开(公告)号：US20170275350A1

    公开(公告)日：2017-09-28

    申请号：US15470117

    申请日：2017-03-27

    申请人： Laurent O. Mosnier ,  John H. Griffin

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

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

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

    摘要： The present invention provides novel PAR1 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 PAR1 sequence. These cytoprotective oligopeptides or polypeptides are capable of activating PAR1 and promoting PAR1 cytoprotective signaling activities. The invention also provides engineered cells or transgenic non-human animals which harbor in their genome an altered PAR1 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 PAR1 derived cytoprotective oligopeptide or polypeptide to treat conditions associated with tissue injuries or undesired apoptosis.

    METHODS FOR THE DETECTION OF CIRCULATING TUMOR CELLS
    19.
    发明申请
    METHODS FOR THE DETECTION OF CIRCULATING TUMOR CELLS 有权
    检测循环肿瘤细胞的方法

    公开(公告)号：US20100247492A1

    公开(公告)日：2010-09-30

    申请号：US12553733

    申请日：2009-09-03

    申请人： Peter Kuhn ,  John H. Griffin ,  Kelly Bethel ,  Dena Marrinucci

    发明人： Peter Kuhn ,  John H. Griffin ,  Kelly Bethel ,  Dena Marrinucci

    IPC分类号： A61K35/12 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/53 ,  A61P35/00

    CPC分类号： G01N33/57492 ,  G01N33/57488 ,  G01N2800/52

    摘要： The present invention provides methods for revealing, detecting, and analyzing circulating tumor cells in the blood of a subject. Revealing detectable circulating tumor cells allows for early stage detection and diagnosis in addition to long term prognosis in subjects with cancer. Additionally, enrichment allows for robust detection and clinically meaningful analysis of low volume samples for use in clinical settings as well as innovative methods for the treatment of cancers.

    摘要翻译： 本发明提供用于揭示，检测和分析受试者血液中的循环肿瘤细胞的方法。 揭示可检测的循环肿瘤细胞除了癌症患者的长期预后之外，还允许进行早期检测和诊断。 此外，富集可以对临床环境中使用的低体积样品进行强大的检测和临床意义的分析，以及治疗癌症的创新方法。

    Oncokinase fusion polypeptides associated with hyperproliferative and related disorders, nucleic acids encoding the same and methods for detecting and identifying the same
    20.
    发明授权
    Oncokinase fusion polypeptides associated with hyperproliferative and related disorders, nucleic acids encoding the same and methods for detecting and identifying the same 有权
    与过度增殖和相关病症相关的肿瘤酶融合多肽，编码其的核酸以及用于检测和鉴定相同的方法

    公开(公告)号：US07585653B2

    公开(公告)日：2009-09-08

    申请号：US11706519

    申请日：2007-02-15

    申请人： Roger Briesewitz ,  John H. Griffin

    发明人： Roger Briesewitz ,  John H. Griffin

    IPC分类号： C12N9/12 ,  C12N15/00 ,  C12N1/20 ,  C07H21/04

    CPC分类号： C07K14/71 ,  C07K2319/00

    摘要： Oncokinase fusion polypeptides associated with hyperproliferative disorders and the polynucleotides encoding for such fusion polypeptides are provided. The fusion polypeptides have a C-terminal tyrosine kinase domain fused to an N-terminal domain that is not normally fused to the C-terminal tyrosine kinase domain and they possess constitutively activated tyrosine kinase activity. Also provided are methods for detecting and identifying the fusion polypeptides and polynucleotides and methods of diagnosing disease conditions associated with the fusion polypeptides and polynucleotides. In addition, screening assays for identifying agents useful for treating disease conditions associated with such fusion polypeptides and polynucleotides are provided. Furthermore, methods of treating disease conditions associated with the presence of the fusion polypeptides are provided.

    摘要翻译： 提供了与过度增殖性病症相关的肿瘤酶融合多肽和编码这种融合多肽的多核苷酸。 融合多肽具有与N末端结构域融合的C-末端酪氨酸激酶结构域，其通常不与C末端酪氨酸激酶结构域融合，并且它们具有组成型激活的酪氨酸激酶活性。 还提供了用于检测和鉴定融合多肽和多核苷酸的方法以及诊断与融合多肽和多核苷酸相关的疾病状况的方法。 此外，提供了用于鉴定用于治疗与这种融合多肽和多核苷酸相关的疾病病症的试剂的筛选试验。 此外，提供了治疗与融合多肽存在相关的疾病状态的方法。