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1. 发明申请

US20150353899A1 USE OF INOS INHIBITORS TO INCREASE VIRAL YIELD IN CULTURE 审中-公开
标题翻译：使用INOS抑制剂增加文化中的病毒感染
公开(公告)号：US20150353899A1
公开(公告)日：2015-12-10
申请号：US14758785
申请日：2014-01-07
申请人： Peter PECHAN , Jeffery ARDINGER , Abraham SCARIA , Samuel WADSWORTH , GENZYME CORPORATION
发明人： Peter Pechan , Jeffery Ardinger , Abraham Scaria , Samuel Wadsworth
IPC分类号： C12N7/00
CPC分类号： C12N7/00 , C12N2710/16643 , C12N2710/16651
摘要： The use of iNOS inhibitors, including aurintricarboxylic acid, dexamethasone and valproic acid, to increase the yield of a variety of viruses in culture, including recombinant herpesviruses is described.
摘要翻译：描述了使用iNOS抑制剂，包括神经三羧酸，地塞米松和丙戊酸，以增加培养物中多种病毒（包括重组疱疹病毒）的产量。

2. 发明申请

US20080070297A1 REGULATORY ELEMENTS FOR DELIVERY TO THE LIVER 审中-公开
标题翻译：向肝脏递送的法规要素
公开(公告)号：US20080070297A1
公开(公告)日：2008-03-20
申请号：US11938906
申请日：2007-11-13
申请人： David SOUZA , Donna ARMENTANO , Samuel WADSWORTH
发明人： David SOUZA , Donna ARMENTANO , Samuel WADSWORTH
IPC分类号： C12N15/861 , C12N15/11
CPC分类号： C12N15/86 , A61K48/00 , A61K48/0058 , C12N15/85 , C12N2710/10343 , C12N2799/022 , C12N2830/008 , C12N2830/15 , C12N2830/85
摘要： The invention is directed to novel combinations of liver specific enhancers and promoter elements for achieving persistent transgene expression in the liver. The liver specific enhancer elements may be derived from either the human serum albumin, prothrombin, α-1microglobulin or aldolase genes in single copies or in multimerized from linked to elements derived from the cytomegalovirus intermediate early (CMV), α-1-antitrypsin or albumin promoters. In a preferred embodiment of the invention, an adenoviral vector comprising a liver specific enhancer/promoter combination operably linked to a transgene is administered to recipient cells. In other embodiments of the invention, adeno-associated viral vectors, retroviral vectors, lentiviral vectors or a plasmid comprising the liver specific enhancer/promoter combination linked to a transgene is administered to recipient cells. Also within the scope of the invention are promoter elements derived from the human prothrombin gene and the β-fibrinogen gene.
摘要翻译：本发明涉及用于实现肝脏中持续转基因表达的肝特异性增强子和启动子元件的新型组合。肝脏特异性增强子元件可以衍生自单拷贝中的人血清白蛋白，凝血酶原，α-1微球蛋白或醛缩酶基因，或与源自巨细胞病毒中间体早期（CMV），α-1-抗胰蛋白酶或白蛋白的元件连接的多聚化发起人。在本发明的优选实施方案中，向受体细胞施用包含可操作地连接到转基因的肝特异性增强子/启动子组合的腺病毒载体。在本发明的其它实施方案中，将腺相关病毒载体，逆转录病毒载体，慢病毒载体或包含与转基因连接的肝特异性增强子/启动子组合的质粒施用于受体细胞。也在本发明范围内的是源自人凝血酶原基因和β-纤维蛋白原基因的启动子元件。

3. 发明授权

US5811633A Transgenic mouse expressing APP.sub.770 失效
标题翻译：转基因小鼠表达APP770
公开(公告)号：US5811633A
公开(公告)日：1998-09-22
申请号：US482027
申请日：1995-06-07
申请人： Samuel Wadsworth , Benjamin Snyder , Cha-Mer Wei , Paul J. Leibowitz
发明人： Samuel Wadsworth , Benjamin Snyder , Cha-Mer Wei , Paul J. Leibowitz
IPC分类号： A01K67/027 , C07K14/47 , C12N5/00 , C12N5/10 , C12N15/09 , C12N15/85 , C12N15/90 , C12R1/91 , G01N33/48 , C12N15/00
CPC分类号： C12N15/8509 , A01K67/0275 , A01K67/0278 , C07K14/4711 , C12N15/90 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/20 , A01K2227/105 , A01K2267/0312 , C12N2830/008
摘要： The construction of transgenic mouse models for testing potential treatments for Alzheimer's disease are described. The models are characterized by a greater similarity to the conditions existing in naturally occurring Alzheimer's disease, based on expression of all three forms of the .beta.-amyloid precursor protein (APP), APP.sub.695, APP.sub.751, and APP.sub.770), as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, and predicted mutations in the APP gene. The APP gene constructs are prepared using the naturally occurring promoter, as well as inducible promoters such as the mouse metallothionine promoter, which can be regulated by addition of heavy metals such as zinc to the mouse's water or diet, and promoters such as the rat neuron specific enolase promoter, human .beta. actin gene promoter, human platelet derived growth factor B (PDGF-B) chain gene promoter, rat sodium channel gene promoter, mouse myelin basic protein gene promoter, human copper-zinc superoxide dismutase gene promoter, and mammalian POU-domain regulatory gene promoter. The constructs are introduced into mouse embryos using standard techniques such as microinjection. Mouse cells can be isolated from the transgenic mice or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic mice, or mouse cells, are used to screen for compounds altering the pathological course of Alzheimer's Disease as measured by their effect on the amount and histopathology of APP and .beta.-amyloid peptide in the mice, as well as by behavioral alterations.
摘要翻译：描述了用于测试阿尔茨海默病潜在治疗的转基因小鼠模型的构建。基于所有三种形式的β-淀粉样蛋白前体蛋白（APP），APP695，APP751和APP770的表达，模型的特征在于与天然存在的阿尔茨海默病中存在的条件更相似，以及各种点突变基于天然存在的突变，例如在氨基酸717处的伦敦和印第安纳家族性阿尔茨海默氏病（FAD）突变，以及APP基因中的预测突变。 APP基因构建体使用天然存在的启动子以及诱导型启动子如小鼠金属硫蛋白启动子制备，其可以通过向小鼠的水或饮食中加入重金属如锌来调节，以及启动子如大鼠神经元特异性烯醇化酶启动子，人β肌动蛋白基因启动子，人血小板衍生生长因子B（PDGF-B）链基因启动子，大鼠钠通道基因启动子，小鼠髓鞘碱性蛋白基因启动子，人铜 - 锌超氧化物歧化酶基因启动子和哺乳动物POU 域调控基因启动子。使用诸如显微注射的标准技术将构建体引入小鼠胚胎。可以从转基因小鼠中分离小鼠细胞，或者使用具有标准技术如脂质转染或电穿孔的相同构建体来制备小鼠细胞。转基因小鼠或小鼠细胞用于筛选通过其对小鼠中APP和β-淀粉样蛋白肽的量和组织病理学的影响以及通过行为改变测量的改变阿尔茨海默氏病病理过程的化合物。

4. 发明授权

US5604131A cDNA-genomic DNA hybrid sequence encoding APP770 containing a genomic DNA insert of the KI and OX-2 regions 失效
标题翻译：编码APP770的cDNA-基因组DNA杂交序列，其含有KI和OX-2区域的基因组DNA插入片段
公开(公告)号：US5604131A
公开(公告)日：1997-02-18
申请号：US123702
申请日：1993-09-17
申请人： Samuel Wadsworth , Benjamin Snyder , Vermuri B. Reddy , Chamer Wei
发明人： Samuel Wadsworth , Benjamin Snyder , Vermuri B. Reddy , Chamer Wei
IPC分类号： C07K14/47 , C12N15/85 , C12N15/90 , C07H21/04 , C12N15/12 , C12N15/63
CPC分类号： C12N15/8509 , A01K67/0278 , C07K14/4711 , C12N15/90 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/0312
摘要： A nucleic acid construct is described which when expressed in cells, results in the production of APP695, APP751 and APP770. The construct is the cDNA for APP770 with the genomic sequences encoding the KI and OX-2 regions substituting for those regions present in the cDNA.
摘要翻译：描述了当在细胞中表达时产生APP695，APP751和APP770的核酸构建体。该构建体是APP770的cDNA，其具有代替存在于cDNA中的那些区域的编码KI和OX-2区域的基因组序列。

5. 发明申请

US20090286857A1 GENE THERAPY FOR AMYOTROPHIC LATERAL SCLEROSIS AND OTHER SPINAL CORD DISORDERS 有权
标题翻译：脊柱侧凸性脊柱炎及其他脊髓损伤的基因治疗
公开(公告)号：US20090286857A1
公开(公告)日：2009-11-19
申请号：US12417910
申请日：2009-04-03
申请人： Catherine O'Riordan , Samuel Wadsworth
发明人： Catherine O'Riordan , Samuel Wadsworth
IPC分类号： A61K31/711 , C12N15/63
CPC分类号： C12N15/86 , A61K38/1709 , A61K48/005 , A61K48/0075 , C07K2319/00 , C12N2750/14143 , C12N2750/14145 , C12N2810/6027 , C12N2830/002 , C12N2830/15
摘要： This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant viral vector containing the transgene to the spinal cord. The viral vector delivers the transgene which expresses the encoded recombinant viral gene product. The viral gene product comprises HIF1-alpha. Also provided are compositions for delivery of a transgene product to a subject's spinal cord.
摘要翻译：本公开提供了用于治疗影响受试者的运动功能和控制的疾病或损伤的方法和组合物。一方面，本发明通过向脊髓施用含有转基因的重组病毒载体将转基因产物递送至受试者的脊髓。病毒载体递送表达编码的重组病毒基因产物的转基因。病毒基因产物包含HIF1-α。还提供了用于将转基因产物递送至受试者的脊髓的组合物。

6. 发明申请

US20110268735A1 MULTIMERIC CONSTRUCTS 有权
标题翻译：多媒体构造
公开(公告)号：US20110268735A1
公开(公告)日：2011-11-03
申请号：US13019432
申请日：2011-02-02
申请人： Abraham Scaria , Peter Pechan , Samuel Wadsworth
发明人： Abraham Scaria , Peter Pechan , Samuel Wadsworth
IPC分类号： A61K39/395 , C12N5/071 , C12N15/85 , C07K16/22 , A61P11/06 , A61K31/7088 , A61P27/02 , A61P3/10 , A61P19/02 , A61P35/00 , C12P21/00 , C07H21/04
CPC分类号： C07K16/22 , A61K38/00 , C07K14/475 , C07K14/52 , C07K14/705 , C07K2319/30 , C07K2319/32 , C07K2319/735 , C12P21/00
摘要： Multimeric fusion proteins of an Ig-like domain of Flt-1 are rendered functional by inclusion of a linker moiety. Vectors encoding the fusion proteins and host cells expressing the fusion proteins can be used therapeutically to block neovascularization in individuals with pathological conditions related to neovascularization. Such conditions include age-related macular degeneration, cancer, psoriasis, proliferative diabetic retinopathy, asthma, uveitis, osteoarthritis, and rheumatoid arthritis. The same means of multimerization used for an Iglike domain of Flt-1, i.e., a linker and a multimerization domain, can be used for other polypeptides, including extracellular receptors, antibody variable regions, cytokines, chemokines, and growth factors.
摘要翻译： Flt-1的Ig样结构域的多聚体融合蛋白通过包含连接体部分而被赋予功能。编码融合蛋白和表达融合蛋白的宿主细胞的载体可用于治疗性地阻断具有与新血管形成相关的病理状况的个体的新生血管形成。这些病症包括年龄相关性黄斑变性，癌症，牛皮癣，增殖性糖尿病性视网膜病变，哮喘，葡萄膜炎，骨关节炎和类风湿性关节炎。用于Flt-1的Ig型结构域，即接头和多聚化结构域的相同的多聚化方法可用于其它多肽，包括细胞外受体，抗体可变区，细胞因子，趋化因子和生长因子。

7. 发明申请

US20050107318A1 Methods of treating diabetes and other blood sugar disorders 审中-公开
标题翻译：治疗糖尿病和其他血糖障碍的方法
公开(公告)号：US20050107318A1
公开(公告)日：2005-05-19
申请号：US10715976
申请日：2003-11-17
申请人： Samuel Wadsworth , Donna Armentano , Richard Gregory , Geoffrey Parsons
发明人： Samuel Wadsworth , Donna Armentano , Richard Gregory , Geoffrey Parsons
IPC分类号： A61K48/00 , C12N15/861
CPC分类号： C12N15/86 , A61K48/00 , A61K48/005 , C12N2710/10343 , C12N2830/002 , C12N2830/85
摘要： Evidence is emerging that lipid accumulation in the liver and the muscle contributes to insulin resistance in type II diabetes and the metabolic syndrome (1). This has prompted an investigation of the relationship between lipid accumulation in the liver, serum triglyceride levels, and glucose disposal. These studies demonstrate that liver fat positively correlated to fasting triglyceride levels and negatively correlated to glucose diposal (2). Therefore, strategies to prevent lipid accumulation in liver would have therapeutic value for treatment of type II diabetes, metabolic syndrome and non-alcoholic fatty liver disease. The invention described here relates to continuous administration of GLP-1 or its analogs obtained by either gene or cell therapy that results in reduction serum triglycerides and reduction of lipid accumulation in the liver for treatment of type II diabetes, the metabolic syndrome or non-alcoholic fatty liver disease.
摘要翻译：证据表明肝脏和肌肉中的脂质积累有助于II型糖尿病和代谢综合征中的胰岛素抵抗（1）。这有助于调查肝脏脂质积累，血清甘油三酯水平和葡萄糖处置之间的关系。这些研究表明，肝脏脂肪与空腹甘油三酯水平呈正相关，与葡萄糖二次分泌呈负相关（2）。因此，预防肝脏脂质积聚的策略对治疗II型糖尿病，代谢综合征和非酒精性脂肪性肝病具有治疗价值。本文描述的发明涉及通过基因或细胞疗法获得的GLP-1或其类似物的连续施用，其导致血清甘油三酯的降低和肝脏中脂质积聚的减少以用于治疗II型糖尿病，代谢综合征或非酒精性脂肪肝病。

8. 发明授权

US08658602B2 Multimeric constructs 有权
标题翻译：多聚体构建体
公开(公告)号：US08658602B2
公开(公告)日：2014-02-25
申请号：US13019432
申请日：2011-02-02
申请人： Abraham Scaria , Peter Pechan , Samuel Wadsworth
发明人： Abraham Scaria , Peter Pechan , Samuel Wadsworth
IPC分类号： C12P21/04 , C12N15/00 , C12N9/48 , A61K38/17 , C07K14/705 , C07K14/71 , C07H21/04
CPC分类号： C07K16/22 , A61K38/00 , C07K14/475 , C07K14/52 , C07K14/705 , C07K2319/30 , C07K2319/32 , C07K2319/735 , C12P21/00
摘要： Multimeric fusion proteins of an Ig-like domain of Flt-1 are rendered functional by inclusion of a linker moiety. Vectors encoding the fusion proteins and host cells expressing the fusion proteins can be used therapeutically to block neovascularization in individuals with pathological conditions related to neovascularization. Such conditions include age-related macular degeneration, cancer, psoriasis, proliferative diabetic retinopathy, asthma, uveitis, osteoarthritis, and rheumatoid arthritis. The same means of multimerization used for an Iglike domain of Flt-1, i.e., a linker and a multimerization domain, can be used for other polypeptides, including extracellular receptors, antibody variable regions, cytokines, chemokines, and growth factors.
摘要翻译： Flt-1的Ig样结构域的多聚体融合蛋白通过包含连接体部分而被赋予功能。编码融合蛋白和表达融合蛋白的宿主细胞的载体可用于治疗性地阻断具有与新血管形成相关的病理状况的个体的新生血管形成。这些病症包括年龄相关性黄斑变性，癌症，牛皮癣，增殖性糖尿病性视网膜病变，哮喘，葡萄膜炎，骨关节炎和类风湿性关节炎。用于Flt-1的Ig型结构域，即接头和多聚化结构域的相同的多聚化方法可用于其它多肽，包括细胞外受体，抗体可变区，细胞因子，趋化因子和生长因子。

9. 发明申请

US20110034539A1 METHODS FOR TREATING BLOOD COAGULATION DISORDERS 审中-公开
标题翻译：治疗血液凝血障碍的方法
公开(公告)号：US20110034539A1
公开(公告)日：2011-02-10
申请号：US12566831
申请日：2009-09-25
申请人： Samuel WADSWORTH , Abraham SCARIA
发明人： Samuel WADSWORTH , Abraham SCARIA
IPC分类号： A61K31/713 , A61P7/02
CPC分类号： C12N9/6437 , A61K48/00 , C07K2319/02 , C12N2799/021 , C12Y304/21021
摘要： The present invention relates to a method of treating an individual having a blood coagulation defect (e.g., hemophilia A, hemophilia B), comprising administering to the individual an effective amount of a DNA vector encoding modified Factor VII (FVII), wherein the modified Factor VII leads to generation of Factor VIIa in vivo. In a particular embodiment, the invention pertains to a method of treating an individual having a blood coagulation defect comprising administering to the individual an effective amount of a nucleic acid encoding a modified FVII wherein the modified FVII comprises a signal which codes for precursor cleavage by furin at the activation cleavage site of the modified FVII. The invention also relates to a method of treating an individual having a blood coagulation disorder comprising administering to the individual an effective amount of a nucleic acid encoding the light chain of human FVII and a nucleic acid encoding the heavy chain of human FVII operably linked to a leader sequence. Compositions, expression vectors and host cells comprising nucleic acid which encodes a modified Factor VII, wherein the modified Factor VII leads to generation of Factor VIIa in vivo is also encompassed by the present invention.
摘要翻译：本发明涉及一种治疗患有血液凝固缺陷的个体（例如，血友病A，血友病B）的方法，包括向个体施用有效量的编码修饰因子VII（FVII）的DNA载体，其中修饰因子 VII导致体内因子VIIa的产生。在一个具体实施方案中，本发明涉及治疗具有凝血缺陷的个体的方法，其包括向个体施用有效量的编码修饰的FVII的核酸，其中修饰的FVII包含编码弗林蛋白酶前体切割的信号在修饰的FVII的激活切割位点。本发明还涉及一种治疗患有血液凝固病症的个体的方法，包括向个体施用有效量的编码人FVII轻链的核酸和编码人FVII重链的核酸，其可操作地连接到领导序列。包含编码修饰因子VII的核酸的组合物，表达载体和宿主细胞，其中修饰的因子VII导致体内产生因子VIIa也包括在本发明中。

10. 发明授权

US09890394B2 Gene therapy for amyotrophic lateral sclerosis and other spinal cord disorders 有权
公开(公告)号：US09890394B2
公开(公告)日：2018-02-13
申请号：US12417910
申请日：2009-04-03
申请人： Catherine O'Riordan , Samuel Wadsworth
发明人： Catherine O'Riordan , Samuel Wadsworth
IPC分类号： A61K31/70 , C12N15/00 , A61K39/00 , C12N15/86 , A61K38/17 , A61K48/00
CPC分类号： C12N15/86 , A61K38/1709 , A61K48/005 , A61K48/0075 , C07K2319/00 , C12N2750/14143 , C12N2750/14145 , C12N2810/6027 , C12N2830/002 , C12N2830/15
摘要： This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant viral vector containing the transgene to the spinal cord. The viral vector delivers the transgene which expresses the encoded recombinant viral gene product. The viral gene product comprises HIF1-alpha. Also provided are compositions for delivery of a transgene product to a subject's spinal cord.

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