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81. 发明授权

US6013639A G cap-stabilized oligonucleotides 失效
标题翻译： G帽稳定的寡核苷酸
公开(公告)号：US6013639A
公开(公告)日：2000-01-11
申请号：US594452
申请日：1996-01-31
申请人： Anuschirwan Peyman , Eugen Uhlmann
发明人： Anuschirwan Peyman , Eugen Uhlmann
IPC分类号： C12N15/09 , A61K31/70 , A61K31/7088 , A61K38/00 , A61P31/12 , A61P35/00 , C07H21/00 , C07H21/04 , C12N15/113 , A61K48/00 , C12Q1/68
CPC分类号： C12N15/113 , C07H21/00 , C12N15/1132 , C12N15/1133 , C12N15/1135 , C12N15/1136 , C12N15/1138 , A61K38/00 , C12N2310/151 , C12N2310/315
摘要： Oligonucleotides of the formula5'-(CAP)-(Oligo)-(CAP)-3'are disclosed where (oligo) is a nucleotide sequence of from 10 to 40 nucleotides in length, and CAP is G.sub.m, where m is an integer of from zero to ten, the two CAP's which are present in the molecule can be defined independently of each other and must be different in the case where m is zero at the 5' or 3' end and the end of the Oligo sequence is other than guanine. The oligonucleotides can be synthesized chemically. The oligonucleotides are used to diagnose or treat cancer, restenosis, a disease caused by a virus, a disease affected by integrins or cell-cell adhesion receptor or a disease triggered by diffusible factors.
摘要翻译：公开了5' - （CAP） - （Oligo） - （CAP）-3'的寡核苷酸，其中（oligo）是长度为10至40个核苷酸的核苷酸序列，CAP为Gm，其中m为整数分子中存在的两个CAP可以彼此独立地定义，并且在5'或3'端的m为零并且Oligo序列的末端是其它的情况下必须是不同的比鸟嘌呤。寡核苷酸可以化学合成。寡核苷酸用于诊断或治疗癌症，再狭窄，由病毒引起的疾病，受整联蛋白或细胞粘附受体影响的疾病或由可扩散因子引发的疾病。

82. 发明授权

US5952490A Oligonucleotides having a conserved G4 core sequence 失效
标题翻译：具有保守G4核心序列的寡核苷酸
公开(公告)号：US5952490A
公开(公告)日：1999-09-14
申请号：US403888
申请日：1995-06-12
申请人： Ronnie C. Hanecak , Kevin P. Anderson , C. Frank Bennett , Ming-Yi Chiang , Vickie L. Brown-Driver , David J. Ecker , Timothy A. Vickers , Jacqueline R. Wyatt , Jean Louis Imbach
发明人： Ronnie C. Hanecak , Kevin P. Anderson , C. Frank Bennett , Ming-Yi Chiang , Vickie L. Brown-Driver , David J. Ecker , Timothy A. Vickers , Jacqueline R. Wyatt , Jean Louis Imbach
IPC分类号： C12N15/09 , A01N63/00 , A61K31/70 , A61K38/00 , A61P31/12 , A61P31/16 , A61P35/00 , C07H21/00 , C07H21/04 , C12N15/113 , C12N15/115 , C12N15/117 , C12P19/34 , C12Q1/68 , C12Q1/70
CPC分类号： A61K31/70 , C07H21/00 , C12N15/1133 , C12N15/1137 , C12N15/115 , C12N15/117 , C12Q1/701 , C12Y207/07049 , C12Y301/01004 , A61K38/00 , C12N2310/151 , C12N2310/18 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346
摘要： Modified oligonucleotides having a conserved G.sub.4 sequence and a sufficient number of flanking nucleotides to significantly inhibit the activity of a virus such as HSV-1 or phospholipase A.sub.2 or to modulate the telomere length of a chromosome are provided. G.sub.4 quartet oligonucleotide structures are also provided. Methods of prophylaxis, diagnosis and therapeutics for viral-associated diseases and diseases associated with elevated levels of phospholipase A.sub.2 are also provided. Methods of modulating telomere length of a chromosome are also provided; modulation of telomere length is believed to plat a role in the aging process of a cell and in control of malignant cell growth.
摘要翻译： PCT No.PCT / US93 / 09297 Sec。 371日期：1995年6月12日 102（e）日期1995年6月12日PCT 1993年9月29日PCT公布。公开号WO94 / 08053 日期1994年04月14日提供了具有保守的G4序列和足够数目的侧翼核苷酸的改变的寡核苷酸以显着抑制病毒如HSV-1或磷脂酶A2的活性或调节染色体的端粒长度。还提供了G4四重态寡核苷酸结构。还提供了与磷脂酶A2水平升高相关的病毒相关疾病和疾病的预防，诊断和治疗方法。还提供了调节染色体端粒长度的方法; 相信端粒长度的调节在细胞衰老过程中起到控制恶性细胞生长的作用。

83. 发明授权

US5932556A Methods and compositions for regulation of CD28 expression 失效
标题翻译：调节CD28表达的方法和组成
公开(公告)号：US5932556A
公开(公告)日：1999-08-03
申请号：US529878
申请日：1995-09-18
申请人： Robert C Tam
发明人： Robert C Tam
IPC分类号： A61K38/00 , A61K48/00 , C12N15/113 , C12N15/11
CPC分类号： C12N15/1138 , A61K38/00 , A61K48/00 , C12N2310/15 , C12N2310/151 , C12N2310/18 , C12N2310/315
摘要： Methods and compositions are provided for the treatment of immune system-mediated diseases. The compositions of the invention have the property of reducing the expression of CD28 in cells of interest so as to moderate the pathogenic effects on the immune system in an immune system-mediated disease. The compositions of the invention include one or more different oligomers capable of reducing the expression of CD28. One aspect of the invention provides oligomers capable of reducing the expression of CD28 by interfering with its expression. The oligomers may be DNA, RNA, or various analogs thereof, and may include 14-50 base phosphorothioates having at least two sequences of GGGG separated by 3 to 5 bases. Other aspects of the invention provide genetic engineering vectors for the intracellular expression of oligomers of the invention in cells of interest, and formulations comprising one or more different oligomers of the invention. The formulations may be adapted for various forms of administration to the body or administration to cells to be reintroduced into the body. The methods of the invention involve modulating CD28 expression through the use of the oligomers of the invention. The methods may be used to treat immune system-mediated diseases and include methods of treating autoimmune disease, methods of reducing an inflammation response, methods of reducing the production of selected cytokines, methods of inactivating T cells, and methods of immunosuppressing a transplant patient.
摘要翻译：提供了用于治疗免疫系统介导的疾病的方法和组合物。本发明的组合物具有降低感兴趣细胞中CD28表达的性质，以便缓解免疫系统介导的疾病对免疫系统的致病作用。本发明的组合物包括能够降低CD28表达的一种或多种不同的低聚物。本发明的一个方面提供能够通过干扰其表达来降低CD28表达的寡聚体。低聚物可以是DNA，RNA或其各种类似物，并且可以包括具有至少两个分开3至5个碱基的GGGG序列的14-50个硫代磷酸酯。本发明的其它方面为感兴趣的细胞中本发明的寡聚体的细胞内表达提供了遗传工程载体，以及包含一种或多种本发明的不同寡聚体的制剂。制剂可以适用于各种给予身体的形式或施用于待再次引入体内的细胞。本发明的方法涉及通过使用本发明的寡聚体调节CD28表达。所述方法可用于治疗免疫系统介导的疾病，并且包括治疗自身免疫性疾病的方法，减少炎症反应的方法，减少所选细胞因子产生的方法，灭活T细胞的方法以及免疫抑制移植患者的方法。

84. 发明授权

US5567604A Anti-viral guanosine-rich oligonucleotides 失效
标题翻译：抗病毒的富含鸟嘌呤的寡核苷酸
公开(公告)号：US5567604A
公开(公告)日：1996-10-22
申请号：US145704
申请日：1993-10-28
申请人： Robert F. Rando , Susan Fennewald , Joseph G. Zendegui , Joshua O. Ojwang
发明人： Robert F. Rando , Susan Fennewald , Joseph G. Zendegui , Joshua O. Ojwang
IPC分类号： C12N15/09 , A61K31/70 , A61K38/00 , A61P31/12 , C07H21/00 , C07H21/04 , C12N15/113 , C12N7/06
CPC分类号： A61K31/70 , A61K31/711 , A61K31/7115 , A61K31/7125 , C07H21/00 , C12N15/1132 , C12N15/1133 , A61K38/00 , C12N2310/151 , C12N2310/18 , C12N2310/315 , C12N2310/321 , C12N2310/33 , C12N2310/335 , C12N2310/351 , C12N2310/3515
摘要： A method and compositions for treating viral infection in vitro and in vivo using a guanosine-rich oligonucleotides. The oligonucleotides are composed of at least about 50% guanosine nucleotides. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity.
摘要翻译：一种用于使用富含鸟苷的寡核苷酸在体外和体内治疗病毒感染的方法和组合物。所述寡核苷酸由至少约50％的鸟苷核苷酸组成。还提供了富含鸟苷的寡核苷酸和用于治疗人类病毒感染的方法，以及设计具有抗病毒活性的富含鸟苷酸的寡核苷酸的方法。

85. 发明申请

WO2015069906A2 MODIFIED DNA QUADRUPLEX-FORMING OLIGONUCLEOTIDES AND METHODS OF USE 审中-公开
标题翻译：修饰的形成DNA的四倍体寡核苷酸及其使用方法
公开(公告)号：WO2015069906A2
公开(公告)日：2015-05-14
申请号：PCT/US2014064361
申请日：2014-11-06
申请人： ADVANCED CANCER THERAPEUTICS LLC , TAPOLSKY GILLES H
发明人： TAPOLSKY GILLES H
IPC分类号： H01L21/3205 , H01L21/02 , H01L21/285
CPC分类号： C12N15/1135 , C07H21/00 , C12N15/1136 , C12N2310/151 , C12N2310/351
摘要： Oligonucleotides according to the following Formula I are provided herein: 5'-X a -Q-Y b -3' wherein X and Y are each independently selected from the group consisting of a lipid and a polyethylene glycol; Q is a quadruplex-forming guanine-rich promoter gene oligonucleotide (GPGO); a is 0 or 1; and b is 0 or 1, wherein the sum of a + b = 1 or 2. Also provided are compositions including Formula I oligonucleotides and methods of their use in inhibiting cell growth, treating cancer, and treating tumors.
摘要翻译：本文提供了根据下式I的寡核苷酸：5'-X a -Q-Y b -3'其中X和Y各自独立地选自脂质和聚乙二醇; Q是四链体形成富含鸟嘌呤的启动子基因寡核苷酸（GPGO）; a是0或1; 并且b是0或1，其中a + b = 1或2的总和。还提供了包含式I寡核苷酸的组合物及其在抑制细胞生长，治疗癌症和治疗肿瘤中使用的方法。

86. 发明申请

WO2009143476A3 NOVEL INHIBITORS OF RETROVIRAL REVERSE TRANSCRIPTASE 审中-公开
标题翻译：新型抗逆转录酶抑制剂
公开(公告)号：WO2009143476A3
公开(公告)日：2010-04-08
申请号：PCT/US2009045057
申请日：2009-05-22
申请人： UNIV MISSOURI , MICHALOWSKI DANIEL , BURKE-AGUERO DONALD H
发明人： MICHALOWSKI DANIEL , BURKE-AGUERO DONALD H
IPC分类号： C07H21/02 , C07H21/04
CPC分类号： C12N15/115 , C12N2310/151 , C12N2310/17 , C12N2310/3519
摘要： Disclosed are nucleic acid molecules, and methods of their use, which have a specific structure including a double helical domain and a G-quadruplex domain physically connected by a linker domain which may be nucleosidic or non-nucleosidic. These aptamers demonstrate potent inhibition of phylogenetically diverse primate lentiviral reverse transcriptases, which effect is largely independent of aptamer sequence provided that the aptamer has the specified structure.
摘要翻译：公开了核酸分子及其使用方法，其具有包括双螺旋结构域和通过可能是核苷或非核苷酸的接头结构域物理连接的G-四链体结构域的特定结构。这些适体表现出对系统发育不同的灵长类动物慢病毒逆转录酶的有效抑制，其效果在很大程度上独立于适体序列，条件是适体具有特定的结构。

87. 发明申请

WO2009143476A2 NOVEL INHIBITORS OF RETROVIRAL REVERSE TRANSCRIPTASE 审中-公开
标题翻译：新型抗逆转录酶抑制剂
公开(公告)号：WO2009143476A2
公开(公告)日：2009-11-26
申请号：PCT/US2009/045057
申请日：2009-05-22
申请人： the CURATORS OF THE UNIVERSITY OF MISSOURI , MICHALOWSKI, Daniel , BURKE-AGUERO, Donald H.
发明人： MICHALOWSKI, Daniel , BURKE-AGUERO, Donald H.
IPC分类号： C12Q1/68 , C07H21/04 , C12N15/63 , C12N5/10
CPC分类号： C12N15/115 , C12N2310/151 , C12N2310/17 , C12N2310/3519
摘要： Disclosed are nucleic acid molecules, and methods of their use, which have a specific structure including a double helical domain and a G-quadruplex domain physically connected by a linker domain which may be nucleosidic or non-nucleosidic. These aptamers demonstrate potent inhibition of phylogenetically diverse primate lentiviral reverse transcriptases, which effect is largely independent of aptamer sequence provided that the aptamer has the specified structure.
摘要翻译：公开了核酸分子及其使用方法，其具有包括双螺旋结构域和通过可能是核苷或非核苷酸的接头结构域物理连接的G-四链体结构域的特定结构。这些适体表现出对系统发育不同的灵长类动物慢病毒逆转录酶的有效抑制，其效果在很大程度上独立于适体序列，条件是适体具有特定的结构。

88. 发明申请

WO2005115359A2 METHODS AND COMPOSITIONS FOR THE TREATMENT OF UVEITIS 审中-公开
标题翻译：治疗UVEITIS的方法和组合
公开(公告)号：WO2005115359A2
公开(公告)日：2005-12-08
申请号：PCT/US2005015761
申请日：2005-05-05
申请人： US GOV HEALTH & HUMAN SERV , KLINMAN DENNIS M , GERY IGAL , FUJIMOTO CHIAKI
发明人： KLINMAN DENNIS M , GERY IGAL , FUJIMOTO CHIAKI
IPC分类号： A61K31/00 , A61K31/7088 , A61K45/06 , C12N15/117
CPC分类号： C12N15/117 , A61K31/7088 , A61K45/06 , C12N2310/151 , C12N2310/17 , C12N2310/18 , C12N2310/315 , A61K2300/00
摘要： Pharmaceutical compositions are disclosed that are of use for the treatment of uveitis. These compositions include a suppressive oligonucleotide. These compositions including an immunosuppressive oligonucleotide can be used for the treatment of uveitis, including anterior, posterior, and diffuse uveitis.
摘要翻译：公开了用于治疗葡萄膜炎的药物组合物。这些组合物包括抑制性寡核苷酸。包括免疫抑制性寡核苷酸的这些组合物可用于治疗葡萄膜炎，包括前，后和弥漫性葡萄膜炎。

89. 发明申请

WO98049288A1 OLIGONUCLEOTIDE MEDIATED SPECIFIC CYTOKINE INDUCTION AND IN VIVO PROTECTION FROM INFECTION 审中-公开
标题翻译：寡核苷酸介导的特异性细胞因子诱导和感染的生物保护
公开(公告)号：WO98049288A1
公开(公告)日：1998-11-05
申请号：PCT/US1998/008751
申请日：1998-04-30
IPC分类号： C12N15/09 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P31/00 , A61P35/00 , C12N15/117 , C12Q1/68 , C12N15/11 , A61K31/70
CPC分类号： C12N15/117 , A61K38/00 , C12N2310/151 , C12N2310/18 , C12N2310/315 , C12N2310/345
摘要： The invention provides methods for modulating specific CMI-inducing cytokines in vivo. Such methods result in stimulation of the cytokines IL-6, IL-12 MIP-1 beta and MCP without substantially inducing undesired cytokines. The methods according to the invention are based upon administration of oligonucleotides containing particular structural motifs which lead to specific cytokine induction.
摘要翻译：本发明提供了在体内调节特异性CMI诱导细胞因子的方法。这种方法导致细胞因子IL-6，IL-12 MIP-1β和MCP的刺激，而基本上不诱导不期望的细胞因子。根据本发明的方法基于施用含有特定结构基序的寡核苷酸，其导致特异性细胞因子诱导。

90. 发明申请

WO1996024380A1 METHODS AND COMPOSITIONS FOR REGULATION OF CD28 EXPRESSION 审中-公开
标题翻译：用于调节CD28表达的方法和组合物
公开(公告)号：WO1996024380A1
公开(公告)日：1996-08-15
申请号：PCT/US1996001507
申请日：1996-02-05
申请人： ICN PHARMACEUTICALS, INC.
发明人： ICN PHARMACEUTICALS, INC. , TAM, Robert, C.
IPC分类号： A61K48/00
CPC分类号： C12N15/1138 , A61K38/00 , A61K48/00 , C12N2310/111 , C12N2310/13 , C12N2310/151 , C12N2310/18 , C12N2310/315
摘要： Oligomers are provided which are capable of reducing CD28 gene in a T cell. In addition to specific sequences, the invention includes a class of oligomers having at least two sequences of GGGG separated by 3 to 5 bases. Targets include CD28 gene, 5' untranslated regions and initiation codon, and their respective transcripts. Methods include use of the oligomers to moderate the pathogenic effects on the immune system in immune system-mediated diseases including graft versus host disease, septic shock syndrome, viral diseases, psoriasis, Type I (insulin-dependent) diabetes mellitus, thyroiditis, sarcoidosis, multiple sclerosis, autoimmune uveitis, rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease.
摘要翻译：提供能够减少T细胞中的CD28基因的寡聚物。除具体序列外，本发明还包括一类具有至少两个分开3至5个碱基的GGGG序列的低聚物。目标包括CD28基因，5'非翻译区和起始密码子，以及它们各自的转录本。方法包括使用寡聚体来抑制免疫系统介导的疾病中的免疫系统的致病作用，包括移植物抗宿主病，败血性休克综合征，病毒性疾病，牛皮癣，I型（胰岛素依赖性）糖尿病，甲状腺炎，结节病，多发性硬化，自身免疫性葡萄膜炎，类风湿性关节炎，系统性红斑狼疮和炎症性肠病。

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