Methods for modulating angiogenesis
    1.
    发明授权
    Methods for modulating angiogenesis 有权
    调节血管生成的方法

    公开(公告)号:US07510714B2

    公开(公告)日:2009-03-31

    申请号:US11668663

    申请日:2007-01-30

    IPC分类号: A61K38/16 A61K38/17

    CPC分类号: A61K38/57

    摘要: Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.

    摘要翻译: 描述了缺乏反应中心环并含有完整的肝素结合结构域或缺乏至少一部分肝素结合结构域的重组纤溶酶原激活物抑制剂-1(PAI-1)异构体。 本文公开的rPAI-1同种型可用于通过从VEGF-肝素复合物阻断VEGF的释放来调节血管生成。 此外,rPAI-1蛋白可用于抑制细胞增殖和迁移,诱导细胞凋亡,并产生对应于血管抑素三酮1-3和三环1-4的蛋白水解片段。 还提供了34kDa的截短的蛋白水解纤溶酶蛋白。

    Methods for modulating angiogenesis via VEGF
    2.
    发明授权
    Methods for modulating angiogenesis via VEGF 有权
    通过VEGF调节血管生成的方法

    公开(公告)号:US07241446B2

    公开(公告)日:2007-07-10

    申请号:US10506225

    申请日:2003-04-01

    IPC分类号: A61K39/00 A61K38/16 A61K38/17

    CPC分类号: A61K38/57

    摘要: Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1–3 and kringles 1–4.

    摘要翻译: 描述了缺乏反应中心环并含有完整的肝素结合结构域或缺乏至少一部分肝素结合结构域的重组纤溶酶原激活物抑制剂-1(PAI-1)异构体。 本文公开的rPAI-1同种型可用于通过从VEGF-肝素复合物阻断VEGF的释放来调节血管生成。 此外,rPAI-1蛋白可用于抑制细胞增殖和迁移,诱导细胞凋亡,并产生对应于血管抑素三酮1-3和三酮酮1-4的蛋白水解片段。

    Phage-display of immunoglobulin heavy chain libraries
    3.
    发明授权
    Phage-display of immunoglobulin heavy chain libraries 失效
    噬菌体展示免疫球蛋白重链文库

    公开(公告)号:US5702892A

    公开(公告)日:1997-12-30

    申请号:US437815

    申请日:1995-05-09

    摘要: One aspect of the invention relates to a phage-display library that expresses single-chain recombinant binding proteins. Inserts in the library comprise immunoglobulin heavy chain framework regions flanking highly divergent, synthetically produced hypervariable regions. A second aspect of the invention relates to the use of single-chain recombinant binding proteins to inhibit the activity of an intracellular constituent. In the exemplary case presented, the activity of intracellular glucose-6-phosphate dehydrogenase was inhibited by intracellular expression of a cloned single-chain recombinant binding protein.

    摘要翻译: 本发明的一个方面涉及表达单链重组结合蛋白的噬菌体展示文库。 文库中的插入片段包含位于高度发散,合成产生的高变区的侧翼的免疫球蛋白重链框架区。 本发明的第二方面涉及使用单链重组结合蛋白来抑制细胞内成分的活性。 在提供的示例性情况下,细胞内葡萄糖-6-磷酸脱氢酶的活性被克隆的单链重组结合蛋白的细胞内表达抑制。

    METHODS FOR INCREASING PLASMIN ACTIVITY AND PROMOTING PLAQUE REGRESSION IN THE TREATMENT OF ATHEROSCLEROSIS
    5.
    发明申请
    METHODS FOR INCREASING PLASMIN ACTIVITY AND PROMOTING PLAQUE REGRESSION IN THE TREATMENT OF ATHEROSCLEROSIS 有权
    方法增加PLASMIN活动和促进骨质疏松症治疗ATHEROSCLEROSIS

    公开(公告)号:US20130310305A1

    公开(公告)日:2013-11-21

    申请号:US13982830

    申请日:2012-02-03

    IPC分类号: A61K38/57

    摘要: The present invention provides the use of recombinant plasminogen activator inhibitor-1 (PAI-1) isoform 23 in methods of increasing plasmin activity, inhibiting angiogenic vasa vasorum, promoting plaque regression and treating atherosclerosis by administering to a subject in need of treatment an effective amount of recombinant plasminogen activator inhibitor type isoform 23 (rPAI-123). In some embodiments, rPAI-123 is set forth in SEQ ID NOs:5-8. In other embodiments, rPAI-123 is administered at a dose in the range of approximately 2.5 μg/kg/day to 20 μg/kg/day. In further embodiments, the effective amount achieves a ratio of rPAI-123 to PAI-1 is in the range of approximately 1:2 to 3:1.

    摘要翻译: 本发明提供重组纤溶酶原激活物抑制剂-1(PAI-1)同种型23在增加纤溶酶活性,抑制血管生成性血管舒张,促进斑块回归和治疗动脉粥样硬化的方法中的用途,其通过对需要治疗的受试者施用有效量 的重组纤溶酶原激活物抑制剂型同种型23(rPAI-123)。 在一些实施方案中,rPAI-123如SEQ ID NO:5-8所示。 在其它实施方案中,rPAI-123以约2.5μg/ kg /天至20ug / kg /天的剂量施用。 在另外的实施方案中,有效量达到rPAI-123与PAI-1的比例在约1:2至3:1的范围内。

    Methods for modulating angiogenesis

    公开(公告)号:US07306803B2

    公开(公告)日:2007-12-11

    申请号:US11403387

    申请日:2006-04-13

    IPC分类号: A61K39/00 A61K38/55 C07K14/81

    CPC分类号: A61K38/57

    摘要: Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.

    Phage-display of immunoglobulin heavy chain libraries for identification
of inhibitors of intracellular constituents
    7.
    发明授权
    Phage-display of immunoglobulin heavy chain libraries for identification of inhibitors of intracellular constituents 失效
    用于鉴定细胞内成分抑制剂的免疫球蛋白重链文库的噬菌体展示

    公开(公告)号:US5824520A

    公开(公告)日:1998-10-20

    申请号:US897040

    申请日:1997-07-19

    摘要: One aspect of the invention relates to a phage-display library that expresses single-chain recombinant binding proteins. Inserts in the library comprise immunoglobulin heavy chain framework regions flanking highly divergent, synthetically produced hypervariable regions. A second aspect of the invention relates to the use of single-chain recombinant binding proteins to inhibit the activity of an intracellular constituent. In the exemplary case presented, the activity of intracellular glucose-6-phosphate dehydrogenase was inhibited by intracellular expression of a cloned single-chain recombinant binding protein.

    摘要翻译: 本发明的一个方面涉及表达单链重组结合蛋白的噬菌体展示文库。 文库中的插入片段包含位于高度发散,合成产生的高变区的侧翼的免疫球蛋白重链框架区。 本发明的第二方面涉及使用单链重组结合蛋白来抑制细胞内成分的活性。 在提供的示例性情况下,细胞内葡萄糖-6-磷酸脱氢酶的活性被克隆的单链重组结合蛋白的细胞内表达抑制。