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    Mutant plasminogen activator-inhibitor type 1 (PAI-1) and uses thereof
    81.
    发明申请
    Mutant plasminogen activator-inhibitor type 1 (PAI-1) and uses thereof 有权
    突变型纤溶酶原激活物抑制剂1型（PAI-1）及其用途

    公开(公告)号：US20030216321A1

    公开(公告)日：2003-11-20

    申请号：US10259609

    申请日：2002-09-30

    申请人： American Red Cross

    发明人： Daniel A. Lawrence ,  Steingrimor P. Stefansson

    IPC分类号： A61K038/08 ,  A61K038/10

    CPC分类号： C07K16/28 ,  A61K38/00 ,  C07K14/8132 ,  C07K2317/77

    摘要： Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notatably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells. Such conditions include atherosclerosis, post angioplasty restenosis, fibrosis associated with chronic inflammation or chemotherapy, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. Also disclosed are peptides of such mutant proteins, mutant-specific antibodies, nucleic acid molecules, particularly DNA, encoding the mutant protein and host cells transformed by such nucleic acids.

    摘要翻译： 描述了人PAI-1蛋白的突变体，其是嗜中性粒细胞弹性蛋白酶抑制剂或玻连蛋白（Vn）依赖性细胞迁移的抑制剂。 这些突变体优选在PAI-1的反应性中心环中，特别是成熟蛋白的位置331和346处包含一个或两个氨基酸取代。 这些突变体在抵抗对Vn具有高亲和力的弹性蛋白酶的失活或两种性质方面是显着的。 作为药物组合物的这些突变蛋白质用于抑制受试者中的弹性蛋白酶，从而治疗与弹性蛋白酶活性，大多数不明显的肺气肿，ARDS，炎症性肺损伤和囊性纤维化相关的许多病症。 与Vn相互作用的突变体用于抑制受试者中的细胞迁移，从而治疗与不期望的细胞迁移和增殖相关的疾病或病症，特别是平滑肌细胞的增殖。 这些病症包括动脉粥样硬化，血管成形术后再狭窄，与慢性炎症或化学疗法相关的纤维化，肿瘤浸润和转移以及血管发生是致病性的病症。 还公开了这样的突变蛋白质，突变体特异性抗体，核酸分子，特别是DNA，编码由这种核酸转化的突变蛋白质和宿主细胞的肽。

    Process for the production of proteins
    82.
    发明授权
    Process for the production of proteins 有权
    蛋白质生产工艺

    公开(公告)号：US06284520B1

    公开(公告)日：2001-09-04

    申请号：US09305723

    申请日：1999-05-05

    申请人： Bernd Meyhack ,  Michael Bröker

    发明人： Bernd Meyhack ,  Michael Bröker

    IPC分类号： C12N119

    CPC分类号： C12N15/81 ,  C07K14/555 ,  C07K14/8132

    摘要： The invention pertains to the field of recombinant DNA technology and concerns a method for the production of a protein heterologous to yeast in a homogenous form with the aid of Saccharomyces cerevisiae strain HT393 or a derivative thereof carrying a hybrid vector containing the genes for said protein.

    摘要翻译： 本发明涉及重组DNA技术领域，涉及一种以酿酒酵母菌株HT393或其携带含有所述蛋白质基因的杂交载体的衍生物，以同质形式产生与酵母异源的蛋白质的方法。

    PAI-1 determination and use thereof
    83.
    发明授权
    PAI-1 determination and use thereof 失效
    PAI-1测定及其应用

    公开(公告)号：US06271352B1

    公开(公告)日：2001-08-07

    申请号：US08466965

    申请日：1995-06-06

    申请人： Lars S. Nielsen ,  Peter Andreasen ,  Keld Dano ,  Nils Brunner

    发明人： Lars S. Nielsen ,  Peter Andreasen ,  Keld Dano ,  Nils Brunner

    IPC分类号： C07K100

    CPC分类号： C07K16/38 ,  C07K14/8132 ,  G01N33/577 ,  G01N33/86 ,  G01N2333/8132

    摘要： a monoclonal antibody which binds a human endothelial type plasminogen activator inhibitor (PAI-1) produced by dexamethasone-treated human HT-1080 fibrosarcoma cells may be used, inter alia, for determining PAI-1 protein abundance in tumor tissue or a sample of a body fluid. Measurements of this parameter may be useful in predicting the presence or metastasis of a tumor, or of predicting the progression of a known malignant tumor.

    摘要翻译： 可以使用结合由地塞米松处理的人HT-1080纤维肉瘤细胞产生的人内皮型纤溶酶原激活物抑制剂（PAI-1）的单克隆抗体，尤其用于测定肿瘤组织中的PAI-1蛋白丰度或 体液。 该参数的测量可用于预测肿瘤的存在或转移，或预测已知恶性肿瘤的进展。

    Mutant plasminogen activator-inhibitor type 1 (PAI-1) and uses thereof
    84.
    发明授权
    Mutant plasminogen activator-inhibitor type 1 (PAI-1) and uses thereof 失效
    突变型纤溶酶原激活物抑制剂1型（PAI-1）及其用途

    公开(公告)号：US6103498A

    公开(公告)日：2000-08-15

    申请号：US840204

    申请日：1997-04-11

    申请人： Daniel A. Lawrence ,  Steingrimur P. Stefansson

    发明人： Daniel A. Lawrence ,  Steingrimur P. Stefansson

    IPC分类号： A61K38/00 ,  C07K14/81 ,  C07K16/28 ,  C12P21/06 ,  C07H21/04 ,  C07K1/00 ,  C12N9/66

    CPC分类号： C07K16/28 ,  C07K14/8132 ,  A61K38/00 ,  C07K2317/77

    摘要： Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells. Such conditions include atherosclerosis, post angioplasty restenosis, fibrosis associated with chronic inflammation or chemotherapy, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. Also disclosed are peptides of such mutant proteins, mutant-specific antibodies, nucleic acid molecules, particularly DNA, encoding the mutant protein and host cells transformed by such nucleic acids.

    摘要翻译： 描述了人PAI-1蛋白的突变体，其是嗜中性粒细胞弹性蛋白酶抑制剂或玻连蛋白（Vn）依赖性细胞迁移的抑制剂。 这些突变体优选在PAI-1的反应性中心环中，特别是成熟蛋白的位置331和346处包含一个或两个氨基酸取代。 这些突变体在抵抗对Vn具有高亲和力的弹性蛋白酶的失活或两种性质方面是显着的。 这些作为药物组合物的突变蛋白质用于抑制受试者中的弹性蛋白酶，从而治疗与弹性蛋白酶活性相关的许多病症，最明显的是肺气肿，ARDS，炎性肺损伤和囊性纤维化。 与Vn相互作用的突变体用于抑制受试者中的细胞迁移，从而治疗与不期望的细胞迁移和增殖相关的疾病或病症，特别是平滑肌细胞的增殖。 这些病症包括动脉粥样硬化，血管成形术后再狭窄，与慢性炎症或化学疗法相关的纤维化，肿瘤浸润和转移以及血管发生是致病性的病症。 还公开了这样的突变蛋白质，突变体特异性抗体，核酸分子，特别是DNA，编码由这种核酸转化的突变蛋白质和宿主细胞的肽。

    Variants of PAI-2
    88.
    发明授权
    Variants of PAI-2 失效
    PAI-2的变体

    公开(公告)号：US5444153A

    公开(公告)日：1995-08-22

    申请号：US768286

    申请日：1991-10-11

    申请人： Neil H. Goss ,  Michael A. Richardson

    发明人： Neil H. Goss ,  Michael A. Richardson

    IPC分类号： G01N33/53 ,  A61K38/55 ,  A61K39/395 ,  A61K49/00 ,  A61K51/00 ,  A61P7/04 ,  A61P29/00 ,  A61P35/00 ,  C07K14/00 ,  C07K14/81 ,  C07K16/00 ,  C07K19/00 ,  C12N1/21 ,  C12N5/10 ,  C12N9/99 ,  C12N15/09 ,  C12N15/15 ,  C12P21/02 ,  C12P21/08 ,  C12R1/19 ,  G01N33/577 ,  C12Q1/00

    CPC分类号： C07K14/8132

    摘要： Variants of the plasminogen activator inhibitor PAI-2 in which the 66-98 amino acid residue region has been altered to eliminate at least one protease sensitive site are provided. The variants of the invention maintain the biological activity of PAI-2 and amino acids up to 65 and from 99 of PAI-2 in frame. The PAI-2 variants of the invention in labelled form, as well as DNA molecules encoding the variants of the invention, transformed host cells expressing the variants of the invention compositions and diagnostic kits comprising the variants of the invention, antibodies against the variants of the invention and processes for the production of the variants, DNA molecules, transformed hosts, compositions and antibodies of the invention are also described.

    摘要翻译： PCT No.PCT / AU90 / 00603 Sec。 371日期1991年10月11日 102（e）日期1991年10月11日PCT 1990年12月20日PCT PCT。 出版物WO91 / 09124 日期：1991年6月27日。提供其中66-98个氨基酸残基区被改变以消除至少一个蛋白酶敏感位点的纤溶酶原激活物抑制剂PAI-2的变体。 本发明的变体在框架中保持PAI-2和PAI-2的最高65和99的氨基酸的生物活性。 标记形式的本发明的PAI-2变体以及编码本发明变体的DNA分子转化表达本发明变体的宿主细胞组合物和包含本发明变体的诊断试剂盒， 还描述了用于生产本发明的变体，DNA分子，转化宿主，组合物和抗体的发明和方法。

    Process for the purification of plasminogen activator inhibitor 2 (PAI-2)
    90.
    发明授权
    Process for the purification of plasminogen activator inhibitor 2 (PAI-2) 失效
    纯化激活剂抑制剂2（PAI-2）的方法

    公开(公告)号：US5204256A

    公开(公告)日：1993-04-20

    申请号：US892634

    申请日：1992-06-02

    申请人： Klaus-Peter Radtke ,  Norbert Heimburger ,  Karlheinz Wenz

    发明人： Klaus-Peter Radtke ,  Norbert Heimburger ,  Karlheinz Wenz

    IPC分类号： C07K14/81

    CPC分类号： C07K14/8132 ,  Y10S435/814

    摘要： A process for the purification of plasminogen activator inhibitor 2 (PAI-2) including the steps of preincubating a PAI-2-containing solution with a compound which cleaves disulfide linkages, mixing the solution with a water-soluble acridine or quinoline base to precipitate impurities in the solution, and separating the precipitated impurities to obtain PAI-2 in purified form.

    摘要翻译： 一种用于纯化纤溶酶原激活物抑制剂2（PAI-2）的方法，包括以下步骤：将含PAI-2的溶液与切割二硫键的化合物预孵育，将溶液与水溶性吖啶或喹啉碱混合以沉淀杂质 在溶液中，分离析出的杂质，得到纯化形式的PAI-2。