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公开(公告)号：US20120027791A1
公开(公告)日：2012-02-02
申请号：US13187338
申请日：2011-07-20
IPC分类号： A61K38/14 , A61P37/06 , C12N5/0784 , C07K9/00 , C12N5/0783 , C12N5/0781
CPC分类号： A61K31/675 , C07K2319/10 , C12N15/1132 , C12N2310/11 , C12N2810/6054
摘要： A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.
摘要翻译： 公开了用于选择性杀死抗原活化的T细胞的方法和缀合物。 缀合物由靶向人cFLIP蛋白的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 相对于缀合物对非活化T细胞的摄取，rTAT多肽有效产生缀合物选择性吸收抗原激活的T细胞。 cFLIP反义化合物引起活化的淋巴细胞活化诱导的细胞死亡（AICD）。 该方法可用于治疗移植排斥反应和自身免疫病症。
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公开(公告)号：US20090111977A1
公开(公告)日：2009-04-30
申请号：US11941033
申请日：2007-11-15
IPC分类号： C07H21/00
CPC分类号： A61K31/675 , C07K2319/10 , C12N15/1132 , C12N2310/11 , C12N2810/6054
摘要： A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.
摘要翻译： 公开了用于选择性杀死抗原活化的T细胞的方法和缀合物。 缀合物由靶向人cFLIP蛋白的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 相对于缀合物对非活化T细胞的摄取，rTAT多肽有效产生缀合物选择性吸收抗原激活的T细胞。 cFLIP反义化合物引起活化的淋巴细胞活化诱导的细胞死亡（AICD）。 该方法可用于治疗移植排斥反应和自身免疫病症。
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公开(公告)号：US08008469B2
公开(公告)日：2011-08-30
申请号：US11941033
申请日：2007-11-15
CPC分类号： A61K31/675 , C07K2319/10 , C12N15/1132 , C12N2310/11 , C12N2810/6054
摘要： A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.
摘要翻译： 公开了用于选择性杀死抗原活化的T细胞的方法和缀合物。 缀合物由靶向人cFLIP蛋白的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 相对于缀合物对非活化T细胞的摄取，rTAT多肽有效产生缀合物选择性吸收抗原激活的T细胞。 cFLIP反义化合物引起活化的淋巴细胞活化诱导的细胞死亡（AICD）。 该方法可用于治疗移植排斥反应和自身免疫病症。
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公开(公告)号：US07989608B2
公开(公告)日：2011-08-02
申请号：US12344143
申请日：2008-12-24
申请人： Dan V. Mourich , Patrick L. Iversen
发明人： Dan V. Mourich , Patrick L. Iversen
CPC分类号： C12N15/1136 , C12N2310/11 , C12N2310/315 , C12N2310/3233
摘要： An antisense oligonucleotide compound, composition, vaccine and methods for treating a variety of conditions characterized by up-regulation of IL-10 in a mammalian subject are disclosed. The compound (i) is composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, (ii) is capable of uptake by monocytes, lymphocytes, and dendritic cells in a mammalian subject, (iii) contains between 10-40 nucleotide bases, and (iv) has a base sequence effective to hybridize to at least 12 contiguous bases of a target sequence contained in an exon-2 or exon-4 slice site region of human IL-10 pre-mRNA.
摘要翻译： 公开了一种反义寡核苷酸化合物，组合物，疫苗和用于治疗特征在哺乳动物受试者中上调IL-10的各种病症的方法。 化合物（i）由吗啉基亚单位和含有一个亚基的吗啉代氮与相邻亚单位的5'环外碳键合的含磷亚基间键组成，（ii）能够被单核细胞，淋巴细胞和树突状细胞吸收 哺乳动物受试者，（iii）含有10-40个核苷酸碱基，和（iv）具有有效杂交到包含在外显子2或外显子-4切片位点区域中的靶序列的至少12个连续碱基的碱基序列 人IL-10前mRNA。
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公开(公告)号：US20090246221A1
公开(公告)日：2009-10-01
申请号：US12344143
申请日：2008-12-24
申请人： Dan V. Mourich , Patrick L. Iversen
发明人： Dan V. Mourich , Patrick L. Iversen
IPC分类号： A61K39/385 , A61K31/7088 , C07H21/00 , A61P37/04
CPC分类号： C12N15/1136 , C12N2310/11 , C12N2310/315 , C12N2310/3233
摘要： An antisense oligonucleotide compound, composition, vaccine and methods for treating a variety of conditions characterized by up-regulation of IL-10 in a mammalian subject are disclosed. The compound (i) is composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, (ii) is capable of uptake by monocytes, lymphocytes, and dendritic cells in a mammalian subject, (iii) contains between 10-40 nucleotide bases, and (iv) has a base sequence effective to hybridize to at least 12 contiguous bases of a target sequence contained in an exon-2 or exon-4 slice site region of human IL-10 pre-mRNA.
摘要翻译： 公开了一种反义寡核苷酸化合物，组合物，疫苗和用于治疗特征在哺乳动物受试者中上调IL-10的各种病症的方法。 化合物（i）由吗啉基亚单位和含有一个亚基的吗啉代氮与相邻亚单位的5'环外碳键合的含磷亚基间键组成，（ii）能够被单核细胞，淋巴细胞和树突状细胞吸收 哺乳动物受试者，（iii）含有10-40个核苷酸碱基，和（iv）具有有效杂交到包含在外显子2或外显子-4切片位点区域中的靶序列的至少12个连续碱基的碱基序列 人IL-10前mRNA。
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公开(公告)号：US09238042B2
公开(公告)日：2016-01-19
申请号：US13107528
申请日：2011-05-13
IPC分类号： A61K49/00 , C12Q1/70 , A61K31/713 , C12N15/113 , A01K67/027 , G01N33/50 , G01N33/569 , G01N33/68
CPC分类号： A61K31/713 , A01K67/027 , A01K2267/03 , C12N15/1136 , C12N15/1138 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/33 , G01N33/5041 , G01N33/56983 , G01N33/6893 , G01N2333/005 , G01N2333/54 , G01N2500/00 , Y02A50/414
摘要： Provided are antisense oligonucleotides and other agents that target and modulate IL-17 and/or IL-23 signaling activity in a cell, compositions that comprise the same, and methods of use thereof. Also provided are animal models for identifying agents that modulate 17 and/or IL-23 signaling activity.
摘要翻译： 提供靶向和调节细胞中IL-17和/或IL-23信号传导活性的反义寡核苷酸和其它试剂，包含其的组合物及其使用方法。 还提供了用于鉴定调节17和/或IL-23信号传导活性的药剂的动物模型。
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7.发明授权Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis 有权用于调节接触性超敏反应或接触性皮炎的反义成分和方法公开(公告)号：US08592386B2
公开(公告)日：2013-11-26
申请号：US12641159
申请日：2009-12-17
CPC分类号： C12N15/1136 , A61K31/7125 , A61K38/19 , A61K45/06 , C12N15/1135 , C12N2310/11 , C12N2310/3513 , C12N2320/32
摘要： Provided are methods and compositions, including topical compositions, for inducing tolerance to a sensitizing agent known to provoke contact hypersensitivity in a subject. Included are methods of topically applying to the subject an effective amount of an antisense composition targeting the start site or splice site of a CFLAR mRNA.
摘要翻译： 提供了用于诱导对已知引起受试者的接触超敏反应的敏化剂的耐受性的方法和组合物，包括局部组合物。 包括对局部施用有效量的靶向CFLAR mRNA的起始位点或剪接位点的反义组合物的方法。
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8.发明授权Antisense oligomers and methods for inducing immune tolerance and immunosuppression 有权反义寡聚体和诱导免疫耐受和免疫抑制的方法公开(公告)号：US08415313B2
公开(公告)日：2013-04-09
申请号：US11433033
申请日：2006-05-11
CPC分类号： A61K31/675 , C12N15/1138 , C12N2310/11 , C12N2310/3233 , C12N2310/3513
摘要： A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound, including partially positively charged, containing 12-40 subunits and a base sequence effective to hybridize to a target region within the sequence identified by SEQ ID NO:9, to form a duplex structure between the compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in the cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.
摘要翻译： 公开了一种用于将人树突状细胞诱导到T细胞的抗原特异性激活能力降低的条件下，并且在成熟树突状细胞中细胞外IL-10的产生增加的方法和组合物。 将一群树突状细胞暴露于包含部分带正电荷的基本上不带电荷的反义化合物，其含有12-40个亚单位和碱基序列，其有效地与SEQ ID NO：9所鉴定的序列内的靶区域杂交以形成双链体 化合物和具有至少45℃的Tm的转录物之间的结构。双链体阻断细胞中全长CD86的表达，这又导致T细胞抗原特异性激活的能力降低，并且在 成熟的树突状细胞，细胞外IL-10的产生增加。
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9.发明申请ANTISENSE COMPOSITIONS AND METHODS FOR MODULATING CONTACT HYPERSENSITIVITY OR CONTACT DERMATITIS 有权反应组合物和调节接触高度或接触剂量的方法公开(公告)号：US20100184670A1
公开(公告)日：2010-07-22
申请号：US12641159
申请日：2009-12-17
IPC分类号： A61K38/00 , A61K31/7088
CPC分类号： C12N15/1136 , A61K31/7125 , A61K38/19 , A61K45/06 , C12N15/1135 , C12N2310/11 , C12N2310/3513 , C12N2320/32
摘要： Provided are methods and compositions, including topical compositions, for inducing tolerance to a sensitizing agent known to provoke contact hypersensitivity in a subject. Included are methods of topically applying to the subject an effective amount of an antisense composition targeting the start site or splice site of a CFLAR mRNA.
摘要翻译： 提供了用于诱导对已知引起受试者的接触超敏反应的敏化剂的耐受性的方法和组合物，包括局部组合物。 包括对局部施用有效量的靶向CFLAR mRNA的起始位点或剪接位点的反义组合物的方法。
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10.发明申请METHOD AND ANTISENSE COMPOSITION FOR SELECTIVE INHIBITION OF HIV INFECTION IN HEMATOPOIETIC CELLS 审中-公开用于选择性抑制HEMATOPOIETIC细胞中HIV感染的方法和抗原组合物公开(公告)号：US20080187993A1
公开(公告)日：2008-08-07
申请号：US11940987
申请日：2007-11-15
IPC分类号： C12N5/06
CPC分类号： A61K31/675 , C07K2319/10 , C12N15/1132 , C12N2310/11 , C12N2810/6054
摘要： A method and conjugate for selectively targeting activated hematopoietic cells, e.g., macrophage or T-lymphocyte cells, are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against HIV, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into activated, HIV-infected cells, e.g., activated, HIV-infected macrophage and T-lymphocyte cells. An exemplary embodiment of the invention provides an antisense compound directed to the HIV Vif gene, causing the production of defective HIV virions in an infected individual.
摘要翻译： 公开了用于选择性靶向活化的造血细胞例如巨噬细胞或T淋巴细胞的方法和缀合物。 缀合物由靶向HIV的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 rTAT多肽有效地产生选择性吸收结合物到活化的HIV感染的细胞，例如活化的，HIV感染的巨噬细胞和T淋巴细胞。 本发明的一个示例性实施方案提供了针对HIV Vif基因的反义化合物，导致在受感染个体中产生有缺陷的HIV病毒体。
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