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81. 发明申请

US20120220015A1 COMPOSITIONS AND METHODS FOR PRODUCTION OF AGLYCOSYLATED PLASMINOGEN 审中-公开
标题翻译：用于生产合成的PLASMINOGEN的组合物和方法
公开(公告)号：US20120220015A1
公开(公告)日：2012-08-30
申请号：US13321719
申请日：2010-05-26
申请人： Lynn F. Dickey , John R. Gasdaska , Kevin M. Cox
发明人： Lynn F. Dickey , John R. Gasdaska , Kevin M. Cox
IPC分类号： C12N9/68 , C12N5/10 , A01H5/00 , C12N15/57 , C12N15/82
CPC分类号： A61K38/168 , C12N9/6435 , C12N15/8257 , C12Y304/21007
摘要： Compositions and methods for producing aglycosylated plasminogen (PLG) polypeptides and fragments and variants thereof are provided. Compositions of the invention include isolated nucleic acid molecules encoding aglycosylated PLG polypeptides in which the asparagine (Asn) residue corresponding to residue Asn-289 of the mature human PLG polypeptide has been substituted with an amino acid residue that does not support N-linked glycosylation at that position of the PLG polypeptide, as well as the aglycosylated PLG polypeptides encoded thereby. Expression constructs comprising these PLG-encoding nucleic acid molecules and transgenic plants comprising these expression constructs are also provided. Methods of the invention comprise introducing a PLG-encoding nucleic acid molecule of the invention into a plant of interest and culturing the plant under conditions to produce the aglycosylated PLG polypeptide. The aglycosylated PLG polypeptide allows for significant increases in production and yield of PLG from a plant-based expression system without comprising the ability of the PLG product to be activated to a polypeptide capable of binding fibrin and having serine protease activity, including biologically active plasmin that is also glycosylated. The activated aglycosylated plasmin is useful to treat diseases or conditions associated with a thrombus.
摘要翻译：提供了用于产生糖基化纤溶酶原（PLG）多肽及其片段和变体的组合物和方法。本发明的组合物包括分离的编码糖基化PLG多肽的核酸分子，其中对应于成熟人PLG多肽的残基Asn-289的天冬酰胺（Asn）残基已被不支持N-连接糖基化的氨基酸残基取代 PLG多肽的位置，以及由此编码的糖基化的PLG多肽。还提供了包含编码这些编码PLG的核酸分子和包含这些表达构建体的转基因植物的表达构建体。本发明的方法包括将本发明的编码PLG的核酸分子引入感兴趣的植物中，并在产生糖苷基化的PLG多肽的条件下培养该植物。糖基化的PLG多肽允许来自基于植物的表达系统的PLG的产量和产量的显着增加，而不包括PLG产物被活化到能够结合纤维蛋白并具有丝氨酸蛋白酶活性的多肽的能力，包括生物活性纤溶酶，也被糖基化。活化的糖基化纤溶酶可用于治疗与血栓相关的疾病或病症。

82. 发明申请

US20100021934A1 Perlecan Fragments as Biomarkers of Bone Stromal Lysis 失效
标题翻译： Perlecan片段作为骨基质裂解的生物标志物
公开(公告)号：US20100021934A1
公开(公告)日：2010-01-28
申请号：US12485640
申请日：2009-06-16
申请人： Mary C. Farach-Carson
发明人： Mary C. Farach-Carson
IPC分类号： G01N33/53 , C12N9/74 , C12N9/68 , C12N9/50 , C07K16/40
CPC分类号： G01N33/53 , C07K14/4725 , C07K16/18 , G01N33/57484 , G01N2333/4722 , Y10S436/811
摘要： A method for the detection in a body fluid of perlecan polypeptide fragments that are biomarkers of tumor metastasis, and antibodies for detecting these fragments are described. An immunoassay kit for detecting the presence of these biomarkers in a body fluid, such as serum or urine, is also described.
摘要翻译：描述了用于检测作为肿瘤转移的生物标志物的perlecan多肽片段的体液的检测方法和用于检测这些片段的抗体。还描述了用于检测体液（例如血清或尿液）中这些生物标志物的存在的免疫测定试剂盒。

83. 发明申请

US20050186649A1 Inhibitors of human plasmin derived from the kunitz domains 失效
标题翻译：人类纤溶酶抑制剂衍生自kunitz结构域
公开(公告)号：US20050186649A1
公开(公告)日：2005-08-25
申请号：US11083742
申请日：2005-03-18
申请人： William Markland , Robert Ladner
发明人： William Markland , Robert Ladner
IPC分类号： C12N15/09 , A61K38/55 , A61K38/57 , A61K51/00 , A61P7/04 , C04B35/593 , C07K14/81 , C12N9/68 , C12Q1/37 , C12Q1/56 , C07H21/04 , C12N9/99
CPC分类号： C04B35/5935 , C07K14/8114
摘要： This invention provides: novel proteins, which are homologous to the first Kunitz domain (K1) of lipoprotein-associated coagulation inhibitor (LACI), and which are capable of inhibiting plasmin; uses of such novel proteins in therapeutic, diagnostic, and clinical methods; and polynucleotides that encode such novel proteins.
摘要翻译：本发明提供了与脂蛋白相关凝血抑制剂（LACI）的第一Kunitz结构域（K1）同源的能够抑制纤溶酶的新型蛋白质; 在治疗，诊断和临床方法中使用这种新型蛋白质; 和编码这种新蛋白质的多核苷酸。

84. 发明授权

US6057122A Antiangiogenic peptides polynucleotides encoding same and methods for inhibiting angiogenesis 失效
标题翻译：编码相同的抗血管生成肽多核苷酸和抑制血管发生的方法
公开(公告)号：US6057122A
公开(公告)日：2000-05-02
申请号：US851350
申请日：1997-05-05
申请人： Donald J. Davidson
发明人： Donald J. Davidson
IPC分类号： C12N15/09 , A61K20060101 , A61K35/14 , A61K38/00 , A61K38/04 , A61K38/48 , A61K39/00 , A61K45/00 , A61K48/00 , A61K101/00 , A61P1/04 , A61P15/18 , A61P17/06 , A61P19/02 , A61P27/02 , A61P29/00 , A61P35/00 , A61P43/00 , C07K1/00 , C07K14/00 , C07K14/47 , C07K14/515 , C07K19/00 , C12N20060101 , C12N9/68 , C12N15/02 , C12N15/57 , C12P21/06
CPC分类号： C12N9/6435 , C12Y304/21007 , A61K38/00 , A61K48/00
摘要： Mammalian kringle 5 fragments and kringle 5 fusion proteins are disclosed as a compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.
摘要翻译：公开了哺乳动物kringle 5片段和kringle 5融合蛋白作为治疗血管生成疾病的化合物。还公开了用于抑制血管生成疾病的方法和组合物。

85. 发明授权

US6010880A Inhibitors of human plasmin derived from the kunitz domains 失效
标题翻译：人类纤溶酶抑制剂衍生自kunitz结构域
公开(公告)号：US6010880A
公开(公告)日：2000-01-04
申请号：US676124
申请日：1997-01-07
申请人： William Markland , Robert Charles Ladner
发明人： William Markland , Robert Charles Ladner
IPC分类号： C12N15/09 , A61K38/55 , A61K38/57 , A61K51/00 , A61P7/04 , C04B35/593 , C07K14/81 , C12N9/68 , C12Q1/37 , C12Q1/56 , C07K1/00 , C07H21/04 , C12N1/20 , C12P21/06
CPC分类号： C04B35/5935 , C07K14/8114
摘要： This invention relates to novel mutants of the first Kunitz domain (K.sub.1) of the human lipoprotein-associated coagulation inhibitor (LACI) which inhibit plasmin. The invention also relates to other modified Kunitz domains that inhibit plasmin and to other plasmin inhibitors.
摘要翻译： PCT No.PCT / US95 / 00298 Sec。 371日期1997年1月7日 102（e）日期1997年1月7日PCT 1995年1月11日PCT PCT。公开号WO95 / 18830 日期1995年7月13日本发明涉及抑制纤溶酶的人脂蛋白相关凝血抑制剂（LACI）的第一Kunitz结构域（K1）的新突变体。本发明还涉及抑制纤溶酶和其它纤溶酶抑制剂的其它修饰的Kunitz结构域。

86. 发明授权

US5981484A Antiangiogenic peptides and methods for inhibiting angiogenesis 失效
标题翻译：抗血管生成肽和抑制血管发生的方法
公开(公告)号：US5981484A
公开(公告)日：1999-11-09
申请号：US832087
申请日：1997-04-03
申请人： Donald J. Davidson
发明人： Donald J. Davidson
IPC分类号： A61K38/00 , A61K48/00 , C12N9/68 , A61K38/04
CPC分类号： C12N9/6435 , C12Y304/21007 , A61K38/00 , A61K48/00
摘要： Mammalian kringle 5 peptide fragments are disclosed for treating angiogenic diseases Methods and compositions for inhibiting angiogenic diseases are also disclosed.
摘要翻译：公开了哺乳动物kringle 5肽片段用于治疗血管生成疾病。还公开了用于抑制血管生成疾病的方法和组合物。

87. 发明授权

US5861372A Aggregate angiostatin and method of use 失效
标题翻译：聚集血管抑素及其使用方法
公开(公告)号：US5861372A
公开(公告)日：1999-01-19
申请号：US605598
申请日：1996-02-22
申请人： M. Judah Folkman , Jie Lin , Michael S. O'Reilly
发明人： M. Judah Folkman , Jie Lin , Michael S. O'Reilly
IPC分类号： A61K38/00 , C12N9/68 , A61K38/16 , C07K14/00
CPC分类号： C12N9/6435 , C12Y304/21007 , A61K38/00
摘要： The present invention comprises an aggregate endothelial inhibitor and method of use therefor. The aggregate endothelial inhibitor comprises a protein having a molecular weight of between approximately 45 kilodaltons and 65 kilodaltons as determined by reducing polyacrylamide gel electrophoresis, and having an amino acid sequence substantially similar to that of a murine plasminogen fragment beginning at amino acid number 98 of a murine plasminogen molecule.
摘要翻译：本发明包括聚集的内皮抑制剂及其使用方法。聚集的内皮抑制剂包含通过还原聚丙烯酰胺凝胶电泳测定的具有约45千道尔顿和65千道尔顿之间的分子量的蛋白质，并且具有基本上类似于从氨基酸序列98开始的鼠纤溶酶原片段的氨基酸序列的氨基酸序列鼠纤溶酶原分子。

88. 发明授权

US5776704A Method of detecting angiogenic protein 失效
标题翻译：检测血管生成蛋白的方法
公开(公告)号：US5776704A
公开(公告)日：1998-07-07
申请号：US452260
申请日：1995-05-26
申请人： Michael S. O'Reilly , M. Judah Folkman
发明人： Michael S. O'Reilly , M. Judah Folkman
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K38/43 , A61K48/00 , A61P9/00 , A61P27/02 , A61P29/00 , A61P35/00 , C07H21/04 , C07K14/47 , C12N5/10 , C12N9/68 , C12N15/57 , C12P21/02 , C12P21/08 , C12Q1/02 , G01N33/15 , G01N33/50 , G01N33/574 , G01N33/68 , G01N33/536 , C07K1/20 , C07K14/435
CPC分类号： G01N33/57407 , C12N9/6435 , C12Y304/21007 , G01N33/574 , G01N33/68 , A61K38/00 , A61K48/00
摘要： The present invention is directed to methods of detecting angiostatin protein which is an endothelial cell inhibitor. The angiostatin protein is a protein isolated from blood or urine that is eluted as single peak from C4-reverse phase high performance liquid chromatography. One method of the present invention includes combining a sample suspected of containing angiostatin protein with an antibody which is specific for angiostatin protein. Another method of the present invention includes isolating the protein and detecting the presence of angiostatin protein by performing an endothelial cell proliferation inhibiting assay.
摘要翻译：本发明涉及检测作为内皮细胞抑制剂的血管生成抑素蛋白的方法。血管抑素蛋白是从血液或尿液中分离的蛋白质，其从C4-反相高效液相色谱法洗脱为单峰。本发明的一种方法包括将怀疑含有血管抑素蛋白的样品与血管抑素蛋白特异的抗体组合。本发明的另一种方法包括通过进行内皮细胞增殖抑制试验来分离蛋白质并检测血管抑素蛋白的存在。

89. 发明授权

US5739281A Interative method of at least three cycles for the refolding of proteins 失效
标题翻译：蛋白质重折叠至少三个循环的交互方法
公开(公告)号：US5739281A
公开(公告)日：1998-04-14
申请号：US469486
申请日：1995-06-06
申请人： Hans Christian Th.o slashed.gersen , Thor Lns Holtet , Michael Etzerodt
发明人： Hans Christian Th.o slashed.gersen , Thor Lns Holtet , Michael Etzerodt
IPC分类号： C12N15/09 , C07D413/14 , C07D471/04 , C07K1/00 , C07K1/04 , C07K1/113 , C07K1/14 , C07K14/005 , C07K14/47 , C07K14/61 , C07K14/705 , C07K14/74 , C07K14/745 , C07K14/81 , C07K16/00 , C07K16/24 , C07K16/46 , C12N9/00 , C12N9/64 , C12N9/68 , C12N15/62 , C12N15/70 , C12P21/02 , C12R1/19 , C07K14/00 , C12P21/00
CPC分类号： C12N9/6435 , C07K1/1136 , C07K1/14 , C07K14/47 , C07K14/61 , C07K14/705 , C07K14/70539 , C07K14/70596 , C07K14/8107 , C07K16/241 , C12N15/62 , C12N15/70 , C12N9/6432 , C12Y304/21006 , C12Y304/21007 , C07K2319/50 , C07K2319/75 , C12N2310/1241 , C12N2310/127
摘要： A novel, generally applicable method for producing correctly folded proteins from a mixture of misfolded proteins, e.g. bacterial inclusion-body aggregates. A major new aspect of the method is that over-all efficiency is achieved by subjecting proteins to a time-sequence of multiple denaturation-renaturation cycles, resulting in gradual accumulation of the correctly folded protein. The method has proven efficient for a variety of recombinant proteins. Also provided are novel encrypted recognition sites for bovine coagulation factor X.sub.a. The encrypted recognition sites described may be activated in vitro by controlled oxidation or by reversible derivatization of cysteine residues and thereby generate new cleavage sites for factor X.sub.a. Two new recombinant serine protease exhibiting narrow substrate specificity for factor X.sub.a recognition sites are also provided. They may replace natural coagulation factor X.sub.a for cleavage of chimeric proteins.
摘要翻译：用于从错误折叠的蛋白质的混合物中产生正确折叠的蛋白质的新颖的，普遍适用的方法，例如。细菌包涵体聚集体。该方法的一个主要新方面是通过使蛋白质经历多个变性 - 复性循环的时间序列来实现全部效率，导致正确折叠的蛋白质的逐渐积累。该方法已被证明对多种重组蛋白有效。还提供了用于牛凝血因子Xa的新型加密识别位点。所描述的加密识别位点可以通过受控氧化或通过半胱氨酸残基的可逆衍生化在体外被激活，从而为因子Xa产生新的切割位点。还提供了两种对因子Xa识别位点具有窄底物特异性的重组丝氨酸蛋白酶。它们可以代替天然凝血因子Xa来切割嵌合蛋白质。

90. 发明授权

US5514572A Method to maintain the activity in polyethylene glycol-modified proteolytic enzymes 失效
标题翻译：保持聚乙二醇修饰蛋白水解酶活性的方法
公开(公告)号：US5514572A
公开(公告)日：1996-05-07
申请号：US256834
申请日：1994-09-19
申请人： Francesco Veronese , Paolo Caliceti , Oddone Schiavon , Sartore Luciana
发明人： Francesco Veronese , Paolo Caliceti , Oddone Schiavon , Sartore Luciana
IPC分类号： C12N9/64 , C12N9/72 , C12N9/76 , C12N9/96 , C12N9/46 , C12N9/48 , C12N9/66 , C12N9/68 , C12N9/70 , C12N9/74
CPC分类号： C12N9/6427 , A61K47/48215 , C07K1/1077 , C12N9/6456 , C12N9/96
摘要： A method for preparing protease-polyethylene glycol adducts is presented wherein the immobilized reversible inhibitor, benzamidine, prevents reaction of activated polyethylene glycol with the active site of the protease. Improved activity against macromolecular substrates is obtained compared to when the benzamidine is in solution during the conjugation reaction.
摘要翻译： PCT No.PCT / EP93 / 00205 Sec。 371日期1994年9月19日 102（e）1994年9月19日PCT 1993年1月29日PCT PCT。公开号WO93 / 15189 日期：1993年8月5日。提出了一种制备蛋白酶 - 聚乙二醇加合物的方法，其中固定的可逆抑制剂苄脒防止活化的聚乙二醇与蛋白酶活性位点的反应。与共轭反应期间苯甲脒在溶液中相比，获得了与大分子底物相反的活性。

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