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公开(公告)号：US5219569A
公开(公告)日：1993-06-15
申请号：US766858
申请日：1985-08-16
IPC分类号： A61K38/00 , C07H21/04 , C12N20060101 , C12N5/10 , C12N9/00 , C12N9/72 , C12N15/00 , C12N15/10 , C12N15/58 , C12N15/67 , C12N15/70 , C12N15/71 , C12P21/02 , C12Q1/00
CPC分类号： C12N9/6462 , C12N15/102 , C12N15/67 , C12N15/71 , C12N9/6459 , C12Y304/21069 , C12Y304/21073 , A61K38/00
摘要： Novel single-chain protease resistant urokinase derivatives are provided. In particular, derivatives are provided wherein the Lys.sub.135 Lys.sub.136 and Arg.sub.156 to Lys.sub.158 sites are rendered less susceptible to proteolytic cleavage are provided by occluding the sites or by covalently modifying them. Preferred covalent modifications are amino acid sequence variants at the sites where proteolysis of urokinase occurs. These are optimally produced by synthesis of single-chain urokinase mutants in recombinant cell culture. The novel urokinase derivatives herein offer the advantage of avoiding the generation of substantial two-chain urokinase, either in vivo or during recombinant cell culture. However, the derivatives continue function to activate plasminogen in initiating blood clot lysis.
摘要翻译： 提供了新的单链蛋白酶抗尿素激酶衍生物。 特别地，提供衍生物，其中Lys135Lys136和Arg156至Lys158位点对蛋白水解切割的敏感性较低是通过闭塞位点或通过共价修饰而提供的。 优选的共价修饰是在发生尿激酶蛋白水解的位点处的氨基酸序列变体。 这些通过在重组细胞培养物中合成单链尿激酶突变体来最佳地产生。 本文中的新型尿激酶衍生物提供了避免在体内或重组细胞培养过程中产生实质的双链尿激酶的优点。 然而，衍生物继续发挥功能以激活纤溶酶原引发血液凝块溶解。
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公开(公告)号：US5112755A
公开(公告)日：1992-05-12
申请号：US221487
申请日：1988-07-19
CPC分类号： C12N9/6462 , C12Y304/21073 , A61K38/00
摘要： Human urokinase is produced using recombinant DNA techniques. The invention disclosed thus enables the production of urokinase free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.
摘要翻译： 使用重组DNA技术产生人尿激酶。 因此，所公开的本发明能够生产没有与其天然细胞环境通常相关的污染物的尿激酶。 还公开了可用于其生产的方法，表达载体和各种宿主细胞。
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公开(公告)号：US5756093A
公开(公告)日：1998-05-26
申请号：US275335
申请日：1994-07-14
CPC分类号： C12N9/6459 , C12Y304/21069 , A61K38/00
摘要： Biologically active variant tissue plasminogen activators are disclosed. The disclosure focuses on position 276 variants that exhibit enhanced fibrin specificity.
摘要翻译： 公开了生物活性变体组织纤溶酶原激活剂。 本公开集中于显示增强的纤维蛋白特异性的位置276变体。
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4.发明授权Human tissue plasminogen activator substituted at position 275 or at positions 275 and 277 失效在275位或275和277位取代的人组织纤溶酶原激活物
公开(公告)号：US5073494A
公开(公告)日：1991-12-17
申请号：US522480
申请日：1990-05-11
CPC分类号： C12N9/6462 , C12N15/102 , C12N15/67 , C12N15/71 , C12N9/6459 , C12Y304/21069 , C12Y304/21073 , A61K38/00
摘要： Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form.
摘要翻译： 公开了生物活性突变组织纤溶酶原激活剂，其中例如双链激活位点的定点诱变使所述突变体对转化为双链形式具有抗性。
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公开(公告)号：US5736134A
公开(公告)日：1998-04-07
申请号：US244773
申请日：1994-08-17
IPC分类号： A61K38/00 , C12N1/21 , C12N9/72 , C12N15/10 , C12N15/67 , C12N15/71 , A61K38/48 , C07H21/04 , C12N9/48
CPC分类号： C12N9/6462 , C12N15/102 , C12N15/67 , C12N15/71 , C12N9/6459 , C12Y304/21069 , C12Y304/21073 , A61K38/00
摘要： Biologically active variant tissue plasminogen activators are disclosed. The disclosure focuses on position 276 variants that exhibit enhanced fibrin specificity.
摘要翻译： PCT No.PCT / US92 / 10677 Sec。 371日期：1994年8月17日 102（e）日期1994年8月17日PCT提交1992年12月14日PCT公布。 出版物WO93 / 12225 日期1994年6月24日公开了生物活性变体组织纤溶酶原激活剂。 本公开集中于显示增强的纤维蛋白特异性的位置276变体。
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公开(公告)号：US5714372A
公开(公告)日：1998-02-03
申请号：US306928
申请日：1994-09-15
CPC分类号： C12N9/6459 , C12Y304/21069 , A61K38/00
摘要： Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form. In addition, mutant tissue plasminogen activators are disclosed which have amino acid substitutions or deletions in the region of positions 274-277, which may or may not be resistant to conversion to the two-chain form, but show enhanced fibrin specificity relative to wild-type tissue plasminogen activator.
摘要翻译： 公开了生物活性突变组织纤溶酶原激活剂，其中例如双链激活位点的定点诱变使所述突变体对转化为双链形式具有抗性。 此外，公开了突变组织纤溶酶原激活剂，其在位置274-277的区域具有氨基酸取代或缺失，其可能或可能不耐转化为双链形式，但相对于野生型的纤维蛋白特异性显示出增强的纤维蛋白特异性， 型组织纤溶酶原激活物。
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7.发明授权Tissue plasminogen activators and derivatives thereof as produced by recombinant means 失效组织纤维蛋白溶酶原激活物及其衍生物，通过重组方法产生
公开(公告)号：US5869314A
公开(公告)日：1999-02-09
申请号：US487456
申请日：1995-06-06
IPC分类号： A61K38/00 , C12N1/21 , C12N9/06 , C12N9/72 , C12N15/58 , C12N15/71 , C12P20060101 , C12N9/64 , A61K38/49
CPC分类号： C12N15/71 , C12N9/003 , C12N9/6459 , C12Y304/21069 , A61K38/00
摘要： Tissue plasminogen activators (t-PAs) and derivatives thereof are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PAs and derivatives thereof via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PAs and derivatives thereof are also disclosed.
摘要翻译： 使用重组DNA技术以有用的量产生组织纤溶酶原激活剂（t-PA）及其衍生物。 具体的衍生物包括氨基酸缺失衍生物和氨基酸取代衍生物。 具有必需的t-PA特征的具体示例是缺少N-末端第68个氨基酸的缺失衍生物。 因此，本发明能够通过重组方法生产t-PA及其衍生物。 还公开了可用于生产所述t-PA及其衍生物的方法，表达载体和各种宿主细胞。
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公开(公告)号：US5618789A
公开(公告)日：1997-04-08
申请号：US829867
申请日：1992-02-03
IPC分类号： A61K38/00 , C07K14/755 , C12N15/10 , C12N15/12 , C12N15/62 , C12N15/85 , C12Q1/68 , A61K38/36 , A61K38/37
CPC分类号： C07K14/755 , C12N15/1034 , C12N15/62 , C12N15/85 , C12Q1/6832 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/80 , C12N2800/108 , C12N2830/00 , C12N2830/55 , C12N2840/105 , C12N2840/44 , Y10S435/948 , Y10S930/10
摘要： Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.
摘要翻译： 重组产生的功能性人因子VIII用于治疗被诊断为缺乏因子VIII凝血活性的人。 还提供了编码功能性人因子VIII的DNA分离物和表达载体，以及通过使用重组DNA技术转化的宿主细胞和用于产生人因子VIII的方法。
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公开(公告)号：USH2181H1
公开(公告)日：2007-02-06
申请号：US07663244
申请日：1991-02-28
申请人： Arthur D. Levinson , Diane Pennica , William J. Kohr , Gordon A. Vehar , David V. Goeddel , Elizabeth M. Yelverton , Christian C. Simonsen
发明人： Arthur D. Levinson , Diane Pennica , William J. Kohr , Gordon A. Vehar , David V. Goeddel , Elizabeth M. Yelverton , Christian C. Simonsen
IPC分类号： C12N15/09
摘要： A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild-type DHFR with methotrexate.
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公开(公告)号：US06284247B1
公开(公告)日：2001-09-04
申请号：US09105681
申请日：1998-06-26
IPC分类号： A61K3848
CPC分类号： C12N15/71 , A61K38/00 , C12N9/003 , C12N9/6459 , C12Y304/21069
摘要： Human tissue plasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.
摘要翻译： 使用重组DNA技术以有用的量产生人组织纤溶酶原激活物（t-PA）。 因此，所公开的发明使得能够生产没有其天然细胞环境中通常相关的污染物的t-PA。 还公开了可用于其生产的方法，表达载体和各种宿主细胞。
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