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    • 7. 发明授权
    • 사람활성화단백질C제제및이의제조방법
    • 사람활성화단백질Ç제제및이의제조방법
    • KR100383063B1
    • 2003-07-07
    • KR1019960702106
    • 1994-10-27
    • 잇빤 자이단호진 가가쿠오요비겟세이료호겐쿠쇼테이진 가부시키가이샤
    • 오가타요이치노우치토시노부나카히라신지
    • C12N9/64
    • C12N9/6464C12Y304/21069Y10S530/83Y10S530/856
    • A human Activated Protein C preparation with a high specific activity being substantially free from thrombin or an equivalent protease and/or Protein C not being subjected to activation and a process for preparing the same are provided. A human Activated Protein C preparation which shows specific activity of 3500 U/mg or more, the unit of specific activity being defined as an amount of APC which prolongs twice an activated thromboplastin time (APTT) of normal human plasma, and is substantially free from thrombin or an equivalent protease and/or Protein C not being subjected to activation. Said preparation is prepared by a process for purification of human Activated Protein C which comprises, after activation of Protein C with thrombin or an equivalent protease, contacting a solution containing human Activated Protein C with a cation exchanger to allow for adsorption of thrombin and Activated Protein C to the exchanger, and then eluting human Activated Protein C alone.
    • 提供具有高比活性的人活化蛋白C制剂基本不含凝血酶或未经活化的等同蛋白酶和/或蛋白质C及其制备方法。 表现出3500U / mg或更高的比活性的人活化蛋白C制剂,比活性单位被定义为延长正常人血浆活化凝血活酶时间(APTT)两倍的APC量,并且基本上不含 凝血酶或相当的蛋白酶和/或蛋白质C未受激活。 所述制剂通过纯化人活化蛋白C的方法制备,所述方法包括在用凝血酶或等效蛋白酶活化蛋白C后,使含有人活化蛋白C的溶液与阳离子交换剂接触以允许吸附凝血酶和活化蛋白 C加入交换器中,然后单独洗脱人活化蛋白C.
    • 9. 发明公开
    • 정상의 세포보호 활성 및 저하된 항응고 활성을 지닌활성화 단백질 C 변이체
    • 具有正常CYTOPROTECTIVE活性的活化蛋白C变体,但降低抗血小板活性
    • KR1020060111442A
    • 2006-10-27
    • KR1020067000567
    • 2004-07-08
    • 더 스크립스 리서치 인스티튜트
    • 그리핀,존,에이치.모스니어,로렌트,오.게일,앤드류,제이.
    • A61K38/36
    • C12Y304/21069A61K38/4866C12N9/6464
    • 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 3K3A-APC and 229/230-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.
    • 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3K3A-APC和229/230-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。