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公开(公告)号：US08852290B2
公开(公告)日：2014-10-07
申请号：US12041651
申请日：2008-03-03
申请人： Adrian P. Rowley , Lucien D. Laude , Mark S. Humayun , James D. Weiland , Atoosa Lotfi , Francis S. Markland, Jr.
发明人： Adrian P. Rowley , Lucien D. Laude , Mark S. Humayun , James D. Weiland , Atoosa Lotfi , Francis S. Markland, Jr.
CPC分类号： A61F2/148 , A61L27/34 , A61L27/50 , A61L2400/18 , A61N1/0543 , A61N1/36 , A61N1/36046 , C08L89/00
摘要： The invention provides a biocompatible silicone implant that can be securely affixed to living tissue through interaction with integral membrane proteins (integrins). A silicone article containing a laser-activated surface is utilized to make the implant. One example is an implantable prosthesis to treat blindness caused by outer retinal degenerative diseases. The device bypasses damaged photoreceptors and electrically stimulates the undamaged neurons of the retina. Electrical stimulation is achieved using a silicone microelectrode array (MEA). A safe, protein adhesive is used in attaching the MEA to the retinal surface and assist in alleviating focal pressure effects. Methods of making and attaching such implants are also provided.
摘要翻译： 本发明提供了一种生物相容的硅氧烷植入物，其通过与整合的蛋白质（整联蛋白）的相互作用可靠地固定在生物体组织上。 使用含有激光激活表面的硅胶制品来制造植入物。 一个例子是用于治疗由视网膜外变性疾病引起的失明的可植入假体。 该装置绕过受损的光感受器并电刺激视网膜的未损伤的神经元。 使用硅微电极阵列（MEA）实现电刺激。 使用安全的蛋白质粘合剂将MEA附着到视网膜表面并有助于减轻焦点压力的影响。 还提供了制造和附接这种植入物的方法。
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2.发明授权Contortrostain (CN) and methods for its use in preventing metastasis and other conditions 失效康帝斯坦（CN）及其用于预防转移和其他病症的方法公开(公告)号：US06710030B1
公开(公告)日：2004-03-23
申请号：US09460295
申请日：1999-12-10
IPC分类号： A61K3800
CPC分类号： A61K38/1703 , C07K14/46
摘要： The amino acid sequence of native contortrostatin was used in a cloning strategy to obtain full-length cDNA and deduced amino acid sequences for a contortrostatin precursor. The precursor includes pro-protein, metalloproteinase, and disintegrin (contortrostatin) regions of the multidomain protein. The sequences can be used produce recombinant DNA molecules which code on expression for contortrostatin proteins, including biologically active variants and fragments. When formulated as a pharmaceutically acceptable composition, the proteins can be used to treat patients by inhibiting disease processes associated with an integrin binding to an integrin receptor.
摘要翻译： 使用天然扭蛋白的氨基酸序列进行克隆策略，以获得全长cDNA并推导出抗雄激素前体的氨基酸序列。 前体包括多结构域蛋白质的前蛋白质，金属蛋白酶和去整合素（扭蛋白酶）区域。 可以使用这些序列产生重组DNA分子，其编码对于停顿蛋白的表达，包括生物活性变体和片段。 当配制成药学上可接受的组合物时，蛋白质可用于通过抑制与整联蛋白结合整联蛋白受体相关的疾病过程来治疗患者。
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3.发明授权Contortrostatin CN and methods for its use in preventing metastasis and other conditions 失效抗抑郁素CN及其用于预防转移和其他病症的方法公开(公告)号：US07220724B2
公开(公告)日：2007-05-22
申请号：US10712584
申请日：2003-11-12
CPC分类号： C07K14/46 , A61K38/1703
摘要： Contortrostatin, a homodimeric disintegrin, modulates the adhesion, motility, and invasiveness of integrin expressing tumor cells. When formulated as a pharmaceutically acceptable composition, the proteins can be used to treat patients by inhibiting or disrupting disease processes associated with an integrin binding to an αvβ3 or αvβ5 integrin.
摘要翻译： 抗扭蛋白，同二聚体解联蛋白，调节整合素表达肿瘤细胞的粘附，运动和侵袭性。 当配制成药学上可接受的组合物时，蛋白质可用于通过抑制或破坏与整合素结合到α1β1或α2β5整联蛋白相关的疾病过程来治疗患者。
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公开(公告)号：US5731288A
公开(公告)日：1998-03-24
申请号：US632691
申请日：1996-04-15
CPC分类号： A61K38/1703 , C07K14/46
摘要： Contortrostatin is employed as active agent for treatment of thrombotic disease. Preferably, contortrostatin is employed in conjunction with at least one thrombolytic agent. In addition, contortrostatin is useful in compositions and methods for preventing metastases in carcinoma and melanoma patients, treating or preventing osteoporosis and promoting wound healing.
摘要翻译： 抗抑郁药被用作治疗血栓性疾病的活性剂。 优选地，止吐剂与至少一种溶栓剂联合使用。 此外，止吐剂可用于预防癌和黑素瘤患者转移的组合物和方法，治疗或预防骨质疏松症和促进伤口愈合。
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5.发明授权Method of expressing proteins with disulfide bridges with enhanced yields and activity 有权用二硫键表达蛋白质的方法，具有增强的产量和活性公开(公告)号：US08802394B2
公开(公告)日：2014-08-12
申请号：US13127970
申请日：2009-11-12
CPC分类号： C12P21/02 , C07K14/46 , C07K2319/35 , C12N9/0036 , C12Y108/01007 , C12Y108/01009
摘要： Provided herein are methods for expressing proteins with disulfide bridges such as Vicrostatin (VCN), a chimeric variant of native snake venom disintegrin Contortrostatin (CN). The methods include what is believed to be a more efficient natural selection process that results in generating increased amounts of correctly-folded active conformers of proteins with disulfide bridges. In an aspect, this is achieved by growing Origami B cells in a more optimal redox environment during the induction of heterologous recombinant protein production.
摘要翻译： 本文提供了用二硫键表达蛋白质的方法，例如Vicrostatin（VCN），天然蛇毒解嵌合素抗旋转蛋白（CN）的嵌合变体。 这些方法包括被认为是更有效的天然选择过程，其导致蛋白质与二硫键正确折叠的活性构象异构体的量增加。 在一方面，这是通过在诱导异源重组蛋白质生产期间在更优化的氧化还原环境中生长折纸B细胞来实现的。
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6.发明授权Inhibiting integrin receptor binding with non-native monomeric disintegrin or monomeric disintegrin domains 有权抑制整合素受体与非天然单体解体蛋白或单克隆蛋白结合域的结合公开(公告)号：US08338365B2
公开(公告)日：2012-12-25
申请号：US13367267
申请日：2012-02-06
CPC分类号： C12P21/00 , A61K38/1703 , C07K14/245 , C07K2319/00 , C07K2319/21 , C07K2319/50 , C07K2319/90 , C12N9/6418 , C12N9/90 , C12P21/02
摘要： This invention relates to methods of inhibiting binding between a cell expressing integrin receptors specific for one or more integrins selected from the group consisting of αIIbβ3, αvβ3, αvβ5, or α5β1, said method comprising contacting the cell with a monomeric disintegrin or monomeric disintegrin domain which comprises a C-terminal sequence non-native to the disintegrin or disintegrin domain, said C-terminal sequence encoding a functional integrin-binding loop.
摘要翻译： 本发明涉及抑制一种表达整合素受体特异性的细胞与选自αIIb和bgr; 3，αv＆bgr; 3，αv＆bgr; 5或α5和bgr之间的结合的方法，所述方法包括使细胞与 单体的整合素或单体的整合蛋白结构域，其包含非整数酶解整合素结构域的C-末端序列，所述C-末端序列编码功能性整联蛋白结合环。
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公开(公告)号：US07754850B2
公开(公告)日：2010-07-13
申请号：US11351311
申请日：2006-02-09
CPC分类号： C12P21/00 , A61K38/1703 , C07K14/245 , C07K2319/00 , C07K2319/21 , C07K2319/50 , C07K2319/90 , C12N9/6418 , C12N9/90 , C12P21/02
摘要： This invention relates to methods of expressing eukaryotic proteins in prokaryotic hosts, particularly eukaryotic proteins that require formation of disulfide bridges for biological activity. Various approaches are used including fusion to thioredoxin, cytoplasmic expression of disulfide isomerases, deficiencies in thioredoxin and/or glutathione reductases, deficiencies in proteases, and the like. The method is applicable to express monomeric and dimeric forms of the eukaryotic protein with biological activity such as monomeric and dimeric forms of a disintegrin or a disintegrin domain. Included are the vectors, host cells expressing the proteins, the expressed proteins and methods of using the proteins.
摘要翻译： 本发明涉及在原核宿主中表达真核蛋白的方法，特别是需要形成用于生物活性的二硫键的真核蛋白。 使用各种方法，包括硫氧还蛋白的融合，二硫键异构酶的细胞质表达，硫氧还蛋白和/或谷胱甘肽还原酶的缺陷，蛋白酶的缺陷等。 该方法适用于表达具有生物学活性的单核和二聚形式的真核生物蛋白，例如单克隆或二聚体形式的解整合素或去整合素结构域。 包括载体，表达蛋白质的宿主细胞，表达的蛋白质和使用蛋白质的方法。
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公开(公告)号：US4610879A
公开(公告)日：1986-09-09
申请号：US568864
申请日：1984-01-06
CPC分类号： C12N9/6418 , A61K38/00
摘要： A protease moiety having direct fibrinolytic activity which is useful in thrombolytic therapy is isolated from snake venom and shown to comprise a metalloproteinase having a molecular weight of from 25 to 27 kd and an isoelectric point of about 6.5 to 7.0. The moiety is separated from venom by a series of diverse fractionation steps including molecular sieve, ion-exchange and affinity chromatography.
摘要翻译： 具有直接纤维蛋白溶解活性的蛋白酶部分可用于溶血溶解治疗，从蛇毒中分离出来，显示出包含分子量为25〜27kD，等电点为约6.5〜7.0的金属蛋白酶。 该部分通过一系列不同的分级步骤从毒液分离，包括分子筛，离子交换和亲和层析。
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公开(公告)号：US08110542B2
公开(公告)日：2012-02-07
申请号：US12831226
申请日：2010-07-06
IPC分类号： A61K38/00 , A61K38/22 , A61K38/36 , C07K14/515 , A61P35/00
CPC分类号： C12P21/00 , A61K38/1703 , C07K14/245 , C07K2319/00 , C07K2319/21 , C07K2319/50 , C07K2319/90 , C12N9/6418 , C12N9/90 , C12P21/02
摘要： This invention relates to methods of expressing eukaryotic proteins in prokaryotic hosts, particularly eukaryotic proteins that require formation of disulfide bridges for biological activity. Various approaches are used including fusion to thioredoxin, cytoplasmic expression of disulfide isomerases, deficiencies in thioredoxin and/or glutathione reductases, deficiencies in proteases, and the like. The method is applicable to express monomeric and dimeric forms of the eukaryotic protein with biological activity such as monomeric and dimeric forms of a disintegrin or a disintegrin domain. Included are the vectors, host cells expressing the proteins, the expressed proteins and methods of using the proteins.
摘要翻译： 本发明涉及在原核宿主中表达真核蛋白的方法，特别是需要形成用于生物活性的二硫键的真核蛋白。 使用各种方法，包括硫氧还蛋白的融合，二硫键异构酶的细胞质表达，硫氧还蛋白和/或谷胱甘肽还原酶的缺陷，蛋白酶的缺陷等。 该方法适用于表达具有生物学活性的单核和二聚形式的真核生物蛋白，例如单克隆或二聚体形式的解整合素或去整合素结构域。 包括载体，表达蛋白质的宿主细胞，表达的蛋白质和使用蛋白质的方法。
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公开(公告)号：US5951981A
公开(公告)日：1999-09-14
申请号：US753781
申请日：1996-12-02
CPC分类号： A61K47/48246 , A61K47/48023 , C12N9/6418
摘要： This invention provides thrombolytic agents and methods for making and using thrombolytic agents. Specifically, the invention provides thrombolytic agents comprising a thrombolytic proteinase and a specific binding peptide that specifically binds at the site of blood clots and thrombi in vivo. The invention particularly provides chemically crosslinked conjugates of a thrombolytic proteinase and a plurality of specific binding peptide. Methods for producing such chemically crosslinked conjugates and methods for using such conjugates for eliminating thrombi in vivo to alleviate pathological conditions caused thereby are also provided. The preferred thrombolytic proteinase in the conjugate is fibrolase obtainable from Agkistrodon contortrix confortrix venom.
摘要翻译： 本发明提供血栓溶解剂和制造和使用溶栓剂的方法。 具体地，本发明提供溶栓剂，其包含在体内血凝块和血栓位置上特异性结合的溶血栓素蛋白酶和特异性结合肽。 本发明特别提供了溶栓酶蛋白酶和多种特异性结合肽的化学交联的缀合物。 还提供了生产这种化学交联共轭物的方法和使用这种缀合物消除体内血栓以减轻由此引起的病理状况的方法。 缀合物中优选的血栓溶解蛋白酶是可从腱蛇毒混合液中获得的纤维素酶。
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