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    Modified factor VII
    3.
    发明授权
    Modified factor VII 失效
    修饰因子VII

    公开(公告)号：US06168789A

    公开(公告)日：2001-01-02

    申请号：US09189607

    申请日：1998-11-10

    申请人： Kathleen L. Berkner ,  Lars Christian Petersen ,  Charles E. Hart ,  Ulla Hedner ,  Claus Bregengaard

    发明人： Kathleen L. Berkner ,  Lars Christian Petersen ,  Charles E. Hart ,  Ulla Hedner ,  Claus Bregengaard

    IPC分类号： A61K3848

    CPC分类号： C12N9/6437 ,  A61K38/166 ,  A61K38/4846 ,  A61K38/49 ,  C12Y304/21021 ,  Y10S514/802 ,  A61K2300/00

    摘要： The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. Pharmaceutical compositions of the modified Factor VII are used to treat a variety of coagulation-related disorders, including platelet deposition, vascular thrombosis, ischemic reperfusion, acute closure of a coronary artery, vascular restenosis secondary to balloon angioplasty, endarterectomy, reductive atherectomy, stent placement, laser therapy or rotablation.

    摘要翻译： 因子VII的催化活性位点被修饰以产生有效中断凝血级联的化合物。 修饰使得因子VIIa基本上不能激活血浆因子X或IX。 修饰因子VII的药物组合物用于治疗各种凝血相关疾病，包括血小板沉积，血管血栓形成，缺血再灌注，冠状动脉急性闭合，继发于球囊血管成形术的血管再狭窄，内膜切除术，还原性粥样斑块切除术，支架置入 ，激光治疗或旋转消融。

    DNA sequence encoding Factor VII with an amino acid substitution at Avg-152
    6.
    发明授权
    DNA sequence encoding Factor VII with an amino acid substitution at Avg-152 失效
    编码因子VII的DNA序列与Avg-152具有氨基酸取代

    公开(公告)号：US5288629A

    公开(公告)日：1994-02-22

    申请号：US951295

    申请日：1992-09-21

    申请人： Kathleen L. Berkner

    发明人： Kathleen L. Berkner

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/43 ,  A61P7/02 ,  C07K14/745 ,  C12N5/10 ,  C12N9/64 ,  C12N15/06 ,  C12N15/57 ,  C12R1/91 ,  C12N5/00 ,  C07H15/12 ,  C07H17/00 ,  C12N15/00

    CPC分类号： C12N9/6437 ,  C12Y304/21021 ,  A61K38/00

    摘要： Factor VII of the coagulation cascade is modified to act as an anticoagulant. Amino acid modifications are employed to produce a modified Factor VII having a substantially reduced susceptibility to activation by enzymes which typically activate wild-type Factor VII. The modified Factor VII is able to compete with wild-type Factor VII and/or VIIa for binding tissue factor, inhibiting clotting activity. As the modified Factor VII acts specifically to interrupt the coagulation cascade, pharmaceutical compositions of modified Factor VII may be administered in place of, or in conjunction with lower doses of, conventional anticoagulant therapies.

    摘要翻译： 将凝血级联的因子VII修饰为抗凝血剂。 使用氨基酸修饰产生修饰的因子VII，其具有通常激活野生型因子VII的酶对活化的敏感性的显着降低。 修饰的因子VII能够与野生型因子VII和/或VIIa竞争结合组织因子，抑制凝血活性。 由于修饰的因子VII特别地用于中断凝血级联，所以修饰因子VII的药物组合物可以代替常规抗凝血剂治疗或与较低剂量的常规抗凝血剂疗法一起施用。

    Expression of protein C
    7.
    发明授权
    Expression of protein C 失效
    蛋白C的表达

    公开(公告)号：US4959318A

    公开(公告)日：1990-09-25

    申请号：US924462

    申请日：1986-10-29

    申请人： Donald C. Foster ,  Mark J. Murray ,  Kathleen L. Berkner

    发明人： Donald C. Foster ,  Mark J. Murray ,  Kathleen L. Berkner

    IPC分类号： C12N5/10 ,  C12N9/64 ,  C12N9/74 ,  C12N15/09 ,  C12N15/12 ,  C12N15/85 ,  C12P21/02 ,  C12R1/91

    CPC分类号： C12N15/85 ,  C12N9/6429 ,  C12N9/6464 ,  C12N9/647 ,  C12Y304/21005 ,  C12Y304/21069 ,  C07K2319/02 ,  Y10S435/849

    摘要： Genomic and cDNA sequences coding for a protein having substantially the same biological activity as human protein C and recombinant transfer vectors comprising these sequences are disclosed.Methods are disclosed for producing a protein which has substantially the same biological activity as human protein C. The protein, which may be in the form of activated protein C, is produced by mammalian host cells transfected with a plasmid capable of integration in mammalian host cell DNA. The plasmid includes a promoter followed downstream by a nucleotide sequence which encodes a protein having substantially the same structure and/or activity as human protein C, the nucleotide sequence being followed downstream by a polyadenylation signal.

    摘要翻译： 公开了编码具有与人蛋白C基本上相同的生物活性的蛋白质的基因组和cDNA序列以及包含这些序列的重组转移载体。 公开了用于生产具有与人蛋白C基本上相同的生物学活性的蛋白质的方法。可以是活化蛋白C形式的蛋白质由用能够整合在哺乳动物宿主细胞中的质粒转染的哺乳动物宿主细胞产生 脱氧核糖核酸。 该质粒包含下游的启动子，后者是编码具有与人蛋白C基本上相同的结构和/或活性的蛋白质的核苷酸序列，该核苷酸序列在多聚腺苷酸化信号的下游。

    Expression of factor VII and IX activities in mammalian cells
    8.
    发明授权
    Expression of factor VII and IX activities in mammalian cells 失效
    因子VII和IX活性在哺乳动物细胞中的表达

    公开(公告)号：US08603777B1

    公开(公告)日：2013-12-10

    申请号：US07765452

    申请日：1991-09-25

    申请人： Frederick S. Hagen ,  Mark J. Murray ,  Sharon J. Busby ,  Kathleen L. Berkner ,  Margaret Y. Insley ,  Richard G. Woodbury ,  Charles L. Gray

    发明人： Frederick S. Hagen ,  Mark J. Murray ,  Sharon J. Busby ,  Kathleen L. Berkner ,  Margaret Y. Insley ,  Richard G. Woodbury ,  Charles L. Gray

    IPC分类号： C12P21/02 ,  C12N5/10

    CPC分类号： C12N9/644 ,  C07K2319/00 ,  C12N2710/10043

    摘要： Methods are disclosed for producing proteins having biological activity for blood coagulation mediated by Factor VIIa or Factor IX. The proteins are produced by mammalian host cells which have been stably transfected with a DNA construct containing a nucleotide sequence which codes at least partially for either Factor VII or Factor IX. The nucleotide sequence comprises a first nucleotide sequence encoding a calcium binding domain, joined to a second nucleotide sequence positioned downstream of the first sequence. The second sequence encodes a catalytic domain for the serine protease activity of either Factor VIIa or Factor IX. The joined sequences code for proteins having substantially the same biological activity for blood coagulation as either Factor VIIa or Factor IX.

    摘要翻译： 公开了用于产生由因子VIIa或因子IX介导的凝血生物活性的蛋白质的方法。 哺乳动物宿主细胞产生的蛋白质已被含有至少部分为因子VII或因子IX编码的核苷酸序列的DNA构建体稳定转染。 核苷酸序列包含编​​码钙结合结构域的第一核苷酸序列，连接到位于第一序列下游的第二核苷酸序列。 第二个序列编码因子VIIa或因子IX的丝氨酸蛋白酶活性的催化结构域。 连接的序列编码与凝血因子VIIa或因子IX具有基本相同的生物活性的蛋白质。

    Modified factor VII anticoagulant proteins
    10.
    发明授权
    Modified factor VII anticoagulant proteins 失效
    修饰因子VII抗凝血蛋白

    公开(公告)号：US5824639A

    公开(公告)日：1998-10-20

    申请号：US152199

    申请日：1993-11-12

    申请人： Kathleen L. Berkner

    发明人： Kathleen L. Berkner

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/43 ,  A61P7/02 ,  C07K14/745 ,  C12N5/10 ,  C12N9/64 ,  C12N15/06 ,  C12N15/57 ,  C12R1/91 ,  A61K38/36 ,  A61K38/48

    CPC分类号： C12N9/6437 ,  C12Y304/21021 ,  A61K38/00

    摘要： Factor VII of the coagulation cascade is modified to act as an anticoagulant. Amino acid modifications are employed to produce a modified Factor VII having a substantially reduced susceptibility to activation by enzymes which typically activate wild-type Factor VII. The modified Factor VII is able to compete with wild-type Factor VII and/or VIIa for binding tissue factor, inhibiting clotting activity. As the modified Factor VII acts specifically to interrupt the coagulation cascade, pharmaceutical compositions of modified Factor VII may be administered in place of, or in conjunction with lower doses of, conventional anticoagulant therapies.

    摘要翻译： 将凝血级联的因子VII修饰为抗凝血剂。 使用氨基酸修饰产生修饰的因子VII，其具有通常激活野生型因子VII的酶对活化的敏感性的显着降低。 修饰的因子VII能够与野生型因子VII和/或VIIa竞争结合组织因子，抑制凝血活性。 由于修饰的因子VII特别地用于中断凝血级联，所以修饰因子VII的药物组合物可以代替常规抗凝血剂治疗或与较低剂量的常规抗凝血剂疗法一起施用。