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1. 发明授权

US07157556B1 Deglycosylated kringle 1-3 region fragments of plasminogen and methods of use 有权
标题翻译：去糖基化的三环纤维蛋白溶酶原区域片段和使用方法
公开(公告)号：US07157556B1
公开(公告)日：2007-01-02
申请号：US09502176
申请日：2000-02-10
申请人： Steven Pirie-Shepherd , M. Judah Folkman , Kim Lee Sim , Nicholas MacDonald , Hong LiAng
发明人： Steven Pirie-Shepherd , M. Judah Folkman , Kim Lee Sim , Nicholas MacDonald , Hong LiAng
IPC分类号： C07K1/00 , C07K14/00 , C07K17/00 , C07K16/00 , A61K35/14 , A61K38/16 , A01N61/00 , C07H21/02
CPC分类号： A61K38/16 , C12N9/6435 , C12Y304/21007
摘要： Disclosed are deglycosylated fragments of a kringle 1-3 region of plasminogen, nucleotides encoding deglycosylated kringle 1-3 region proteins and antibodies specific for deglycosylated kringle 1-3 region proteins. The compositions of the present invention have increased antiangiogenic activity as compared to previously isolated kringle 1-3 region proteins. Also included in the present invention are methods of treating angiogenesis-associated diseases and conditions such as cancer using the compositions described herein.
摘要翻译：公开了纤溶酶原的三环1-3区的去糖基化片段，编码去糖基化的三环1-3区蛋白的核苷酸和对去糖基化的三环1-3区蛋白特异的抗体。与先前分离的三环1-3区蛋白相比，本发明的组合物具有增加的抗血管生成活性。本发明还包括使用本文所述的组合物治疗血管生成相关疾病和病症如癌症的方法。

2. 发明授权

US06607724B2 Compositions and methods for inhibiting angiogenesis 失效
标题翻译：用于抑制血管发生的组合物和方法
公开(公告)号：US06607724B2
公开(公告)日：2003-08-19
申请号：US09414834
申请日：1999-10-08
申请人： Michael S. O'Reilly , M. Judah Folkman , Steven Pirie-Shepherd
发明人： Michael S. O'Reilly , M. Judah Folkman , Steven Pirie-Shepherd
IPC分类号： A61K3900
CPC分类号： G01N33/5088 , A61K38/57 , A61K48/00 , G01N33/5011 , G01N33/5091 , G01N2500/00
摘要： The invention provides for methods of reducing or inhibiting angiogenesis, tumor growth and endothelial cell proliferation by the administration of compositions containing fragments, conformations, biological equivalent, or derivatives of antithrombin III. The invention also provides for pharmaceutical compositions comprising a fragment, conformation, biological equivalent, or derivative of antithrombin III and methods of identifying novel inhibitors of tumor growth, endothelial cell proliferation, and/or angiogenesis. The invention also relates to compositions and methods for altering angiogenesis in a mammal, as well as to methods of treatment for disorders associated with angiogenesis (e.g., cancer).
摘要翻译：本发明提供了通过施用含有抗凝血酶III的片段，构象，生物学等价物或衍生物的组合物来减少或抑制血管生成，肿瘤生长和内皮细胞增殖的方法。本发明还提供包含抗凝血酶III的片段，构象，生物等价物或衍生物的药物组合物和鉴定肿瘤生长，内皮细胞增殖和/或血管发生的新型抑制剂的方法。本发明还涉及用于改变哺乳动物血管发生的组合物和方法，以及治疗与血管生成相关的病症（例如癌症）的方法。

3. 发明申请

US20080031817A1 Inhibition Of Superoxide Dismutase By Tetrathiomolybdate: Identification Of New Anti-Angiogenic And Antitumor Agents 审中-公开
标题翻译：通过四硫钼酸盐抑制超氧化物歧化酶：鉴定新的抗血管生成和抗肿瘤剂
公开(公告)号：US20080031817A1
公开(公告)日：2008-02-07
申请号：US10590483
申请日：2005-02-24
申请人： Andrew P. Mazar , Steven Pirie-Shepherd , Oscar Betancourt
发明人： Andrew P. Mazar , Steven Pirie-Shepherd , Oscar Betancourt
IPC分类号： A61K31/426 , A61K31/428 , A61K31/554 , A61P35/00 , C12N9/99 , C12Q1/26
CPC分类号： G01N33/5011 , C12Q1/26 , G01N2333/90283 , G01N2500/10
摘要： Though copper is elevated in the tumor tissue and plasma of patients with various malignancies, the molecular targets for copper binding agents in angiogenesis and tumor progression remain poorly understood. It is disclosed that one anti-angiogenic target for the copper binding agent tetrathiomolybdate is intracellular CuZn-superoxide dismutase (SOD1). A second generation tetrathiomolybdate analog, ATN-224, inhibits endothelial cell (EC) proliferation in vitro, binds to SOD1 and inhibits its activity without displacing bound copper ATN-224 can accumulate in ECs and inhibit CuZnSOD activity with an IC50 similar to the IC50 for EC proliferation, resulting in increased generation of intracellular reactive oxygen species. Inhibition of EC proliferation by ATN-224 in vitro is substantially reversed by a synthetic porphyrin SOD mimetic. Similar results were observed in vivo, where inhibition of angiogenesis by ATN-224 in a Matrigel plug model was also reversed by MnTBAP. Thus, a distinct molecular target for copper depletion therapy has been identified and SOD1 is now validated as a target for anti-angiogenesis. Methods for screening, or designing, such SOD1 inhibitors for use as angiogenesis inhibitors and anti-cancer agents are disclosed.
摘要翻译：虽然铜在各种恶性肿瘤患者的肿瘤组织和血浆中升高，但铜结合剂在血管生成和肿瘤进展中的分子靶标仍然知之甚少。公开了四硫钼酸铜结合剂的一种抗血管生成靶是细胞内CuZn超氧化物歧化酶（SOD1）。第二代四硫钼酸盐类似物ATN-224在体外抑制内皮细胞（EC）增殖，结合SOD1并且抑制其活性而不排除结合的铜ATN-224可以积累在EC中并且通过IC 50抑制CuZnSOD活性 / SUB>类似于EC增殖的IC 50，导致细胞内活性氧的产生增加。通过ATN-224体外抑制EC增殖基本上被合成的卟啉SOD模拟物逆转。在体内观察到类似的结果，其中Matrigel塞模型中ATN-224的血管生成抑制也被MnTBAP逆转。因此，已经鉴定了用于铜消耗治疗的不同分子靶标，并且SOD1现在被证实为抗血管生成的靶标。公开了用于筛选或设计用于血管生成抑制剂和抗癌剂的这种SOD1抑制剂的方法。

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