公开(公告)号：US09448234B2

公开(公告)日：2016-09-20

申请号：US14358116

申请日：2012-11-15

申请人： National University Corporation Hamamatsu University School of Medicine

发明人： Naohiro Kanayama ,  Kazuo Umemura ,  Takayuki Iwaki ,  Tetsumei Urano ,  Kotomi Ikuma

IPC分类号： G01N33/53 ,  G01N33/543 ,  G01N33/68 ,  A61K38/57 ,  C07K14/81

CPC分类号： G01N33/54306 ,  A61K38/57 ,  C07K14/8132 ,  G01N33/689 ,  G01N2333/8132 ,  G01N2800/368

摘要： A method for diagnosing a risk for preterm delivery or miscarriage in a pregnant woman and preventing preterm delivery or miscarriage in the pregnant woman who has been determined to have the risk is provided. The method includes measuring plasminogen activator inhibitor-1 activity or level in plasma isolated from a pregnant woman. The method also includes determining that the pregnant woman has a risk for preterm delivery or miscarriage when the activity or the level is lower than that in the plasma of a normal pregnant woman. The method also includes administering plasminogen activator inhibitor-1 to the pregnant woman who has been determined to have the risk. A kit for the diagnosis of the degree of risk for preterm delivery or miscarriage also is provided. A pharmaceutical composition for the prevention of preterm delivery or miscarriage, comprising plasminogen activator inhibitor-1, also is provided.

摘要翻译： 提供了一种诊断孕妇早产或流产的风险的方法，并预防已确定有风险的孕妇的早产或流产。 该方法包括测量从孕妇分离的血浆中的纤溶酶原激活物抑制剂-1活性或水平。 该方法还包括当活动或水平低于正常孕妇的血浆中时，确定孕妇具有早产或流产的风险。 该方法还包括对已确定有风险的孕妇施用纤溶酶原激活物抑制剂-1。 还提供了用于诊断早产或流产风险程度的试剂盒。 还提供了用于预防早产或流产的药物组合物，其包含纤溶酶原激活物抑制剂-1。

公开(公告)号：US08828686B2

公开(公告)日：2014-09-09

申请号：US13769144

申请日：2013-02-15

申请人： Intrexon Corporation

发明人： Thomas D. Reed ,  Richard E. Peterson ,  Charles E. Reed ,  Joan Mazzarelli Sopczynski ,  Bethany L. Merenick ,  Jonathan Carson ,  Catherine L. Keaty ,  Elena Tasheva

IPC分类号： C12N15/63 ,  C12N1/20 ,  C07K14/00 ,  C07K14/81 ,  C07K14/75 ,  C07K14/78 ,  C12N9/72 ,  C12N9/44

CPC分类号： C07K14/001 ,  C07K14/75 ,  C07K14/78 ,  C07K14/8132 ,  C12N9/2451 ,  C12N9/6459 ,  C12N9/6462 ,  C12Y302/01099 ,  C12Y304/21069 ,  C12Y304/21073

摘要： The invention relates to mammalian PAI-I ligands and modulators. In particular, the invention relates to polypeptides, polypeptide compositions and polynucleotides that encode polypeptides that are ligands and/or modulators of PAI-I. The invention also relates to polyligands that are homopolyligands or heteropolyligands that modulate PAI-I activity. The invention also relates to ligands and polyligands localized to a region of a cell. The invention also relates to localization tethers and promoter sequences that can be used to provide spatial control of the PAI-I ligands and polyligands. The invention also relates to inducible gene switches that can be used to provide temporal control of the PAI-I ligands and polyligands. The invention also relates to methods of treating or preventing atherosclerosis. The invention also relates to methods of treating or preventing fibrosis.

摘要翻译： 本发明涉及哺乳动物PAI-1配体和调节剂。 具体地，本发明涉及编码作为PAI-1的配体和/或调节剂的多肽的多肽，多肽组合物和多核苷酸。 本发明还涉及作为调节PAI-1活性的均聚配体或杂多糖的聚合配体。 本发明还涉及位于细胞区域的配体和聚合配体。 本发明还涉及可用于提供PAI-1配体和聚合配体的空间控制的定位系链和启动子序列。 本发明还涉及可用于提供PAI-1配体和聚合配体的时间控制的可诱导基因开关。 本发明还涉及治疗或预防动脉粥样硬化的方法。 本发明还涉及治疗或预防纤维化的方法。

公开(公告)号：US20100215636A1

公开(公告)日：2010-08-26

申请号：US12670099

申请日：2008-07-24

申请人： Abd Al-Roof Higazi

发明人： Abd Al-Roof Higazi

IPC分类号： A61K38/10 ,  C07K7/08 ,  A61K38/49 ,  A61P25/00 ,  A61P25/28 ,  A61P25/16

CPC分类号： C07K14/8132 ,  A61K38/00

摘要： The present invention relates to isolated 18-mer peptides corresponding to amino acid residues 369-386 of human plasminogen activator inhibitor 1 (PAI-1) and fragments thereof, compositions that include such peptides, and uses of such compositions for treating thromboembolic diseases and pathological conditions associated with neurological damage.

摘要翻译： 本发明涉及对应于人纤溶酶原激活物抑制剂1（PAI-1）的氨基酸残基369-386及其片段的分离的18聚体肽，包括这些肽的组合物，以及这些组合物用于治疗血栓栓塞性疾病和病理学 与神经损伤相关的病症。

公开(公告)号：US20090136421A1

公开(公告)日：2009-05-28

申请号：US12285767

申请日：2008-10-14

申请人： Marie Ranson ,  Barry John Allen ,  Clive Leighton Bunn

发明人： Marie Ranson ,  Barry John Allen ,  Clive Leighton Bunn

IPC分类号： A61K51/08 ,  A61P35/00

CPC分类号： C07K14/8132 ,  A61K38/00

摘要： A method is described for detecting, visualizing, or treating cells, particularly cancerous cells, that express a uPA/uPAR complex. The method employs a PAI-2 conjugate molecule that comprises PAI-2 or a functional derivative, homologue, analogue, chemical equivalent or mimetic thereof, which PAI-2 is bound, linked, or otherwise associated with a toxin or label.

公开(公告)号：US07388074B2

公开(公告)日：2008-06-17

申请号：US10259609

申请日：2002-09-30

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

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

IPC分类号： A61K38/00

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。

公开(公告)号：US20030217371A1

公开(公告)日：2003-11-20

申请号：US10368995

申请日：2003-02-19

申请人： Vanderbilt University

发明人： Douglas E. Vaughan ,  Mesut Eren ,  Paul J. Declerck

IPC分类号： A61K031/00 ,  C12Q001/68 ,  C07H021/04

CPC分类号： C12N15/873 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0312 ,  C07K14/8132 ,  C12N15/8509 ,  C12Q1/56 ,  G01N33/566 ,  G01N33/68 ,  G01N33/6893 ,  G01N33/6896 ,  G01N33/86 ,  G01N2333/8132 ,  G01N2500/00

摘要： A method of treating a warm-blooded vertebrate animal having a medical condition in need of treatment with a composition that exhibits PAI-1 inhibition activity is disclosed. The method includes the steps of administering a treatment effective amount of the composition to a warm-blooded vertebrate animal having a medical condition selected from the group consisting of alopecia, undesired weight loss, Alzheimer's Disease, systemic amyloidosis, myelofibrosis, male pattern baldness, glomerulosclerosis, and combinations thereof; and observing an improvement in the medical condition in the warm-blooded vertebrate animal having the medical condition. A method of testing a candidate composition for PAI-1 inhibition activity is also disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer overexpression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful is such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.

摘要翻译： 公开了一种治疗需要用表现出PAI-1抑制活性的组合物治疗的具有医学病症的温血脊椎动物的方法。 该方法包括以下步骤：向具有选自脱发，不希望的体重减轻，阿尔茨海默病，全身性淀粉样变性，骨髓纤维化，男性型秃发，肾小球硬化的医学病症的温血脊椎动物施用有效量的组合物 ，及其组合; 并观察具有医疗状况的温血脊椎动物的医疗状况的改善。 还公开了测试候选组合物用于PAI-1抑制活性的方法。 该方法包括以下步骤：获得在其基因组中掺入了编码生物活性PAI-1多肽的PAI-1基因的转基因非人类温血脊椎动物，所述PAI-1基因以有效的拷贝数存在于基因组中 以在PAI-1多肽的转基因非人动物中赋予过表达; 将所述组合物施用于所述转基因非人动物; 并观察转基因非人动物以测定表达PAI-1活性抑制的转基因非人动物的变化。 还公开了一种有用的转基因非人动物，编码可用于制备转基因非人动物的生物活性PAI-1多肽的PAI-1转基因构建体也是公开的。

公开(公告)号：US06649738B2

公开(公告)日：2003-11-18

申请号：US09902684

申请日：2001-07-12

申请人： Jian Ni ,  Reiner L. Gentz ,  Steven M. Ruben

发明人： Jian Ni ,  Reiner L. Gentz ,  Steven M. Ruben

IPC分类号： C07K100

CPC分类号： C07K14/81 ,  A61K38/00 ,  A61K48/00 ,  C07K14/8132 ,  C07K2319/00 ,  Y02A50/463

摘要： The present invention relates to a novel member of the plasminogen activator inhibitor protein family. In particular, isolated nucleic acid molecules are provided encoding the pancreas-derived plasminogen activator inhibitor protein. Pancreas-derived plasminogen activator inhibitor polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to methods for treating physiologic and pathologic disease conditions, including breast cancer, and diagnostic methods for detecting pathologic disorders.

公开(公告)号：US20030199463A1

公开(公告)日：2003-10-23

申请号：US10128706

申请日：2002-04-23

发明人： Silviu Itescu

IPC分类号： A61K048/00 ,  C07H021/02

CPC分类号： C12N15/113 ,  A61K38/00 ,  C07K14/8132 ,  C12N15/1137 ,  C12N2310/12 ,  C12N2310/315

摘要： The present invention provides DNAzymes and ribozymes that specifically cleave PAI-1-encoding mRNA. The present invention also provides antisense oligonucleotides that specifically inhibit translation of PAI-1-encoding mRNA. The invention also provides various methods of inhibiting the expression of PAI-1. Finally the invention provides pharmaceutical compositions containing the instant DNAzymes, ribozymes and antisense oligonucleotides as active ingredients.

摘要翻译： 本发明提供了特异性切割编码PAI-1的mRNA的DNA酶和核酶。 本发明还提供了特异性抑制编码PAI-1的mRNA翻译的反义寡核苷酸。 本发明还提供了抑制PAI-1表达的各种方法。 最后，本发明提供含有本发明酶，核酶和反义寡核苷酸作为活性成分的药物组合物。

公开(公告)号：US06489143B1

公开(公告)日：2002-12-03

申请号：US09324494

申请日：1999-06-02

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

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

IPC分类号： C12N1509

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 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的反应性中心环中包含一个或两个氨基酸取代，特别是在 成熟蛋白质的位置331和346。 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。

公开(公告)号：US5985657A

公开(公告)日：1999-11-16

申请号：US483806

申请日：1995-06-07

申请人： Philip E. Auron ,  Charles A. Dinarello ,  Andrew C. Webb ,  Alexander Rich ,  Sheldon M. Wolff

发明人： Philip E. Auron ,  Charles A. Dinarello ,  Andrew C. Webb ,  Alexander Rich ,  Sheldon M. Wolff

IPC分类号： A61K38/00 ,  A61P43/00 ,  C07K14/545 ,  C07K14/81 ,  C12N1/21 ,  C12N15/25 ,  C12N15/58 ,  C12P21/02 ,  C12P21/04 ,  C07H21/04 ,  C12N5/16 ,  C12N15/85

CPC分类号： C12P21/02 ,  C07K14/545 ,  C07K14/8132 ,  A61K38/00 ,  Y10S930/141

摘要： The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes stimulated with bacterial endotoxin. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells.

摘要翻译： 本发明涉及包含编码人白介素-1（IL-1）及其片段的核苷酸序列的核酸，以及获得的多肽和肽。 具体地，本发明包括通过用细菌内毒素刺激的粘附的人单核细胞分离的聚（A）RNA的逆转录合成的cDNA的克隆。 人IL-1可用于通过活化的T细胞诱导IL-2的产生; 它也作用于B细胞和NK细胞。