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11. 发明申请

US20060178333A1 Antisense oligonucleotide against human acetylcholinesterase (AChE) and uses thereof 有权
公开(公告)号：US20060178333A1
公开(公告)日：2006-08-10
申请号：US11346145
申请日：2006-02-01
申请人： Hermona Soreq , Shlomo Saidman , Jackiline Saidman , Tama Evron
发明人： Hermona Soreq , Shlomo Saidman , Jackiline Saidman , Tama Evron
IPC分类号： A61K48/00 , C07H21/04
CPC分类号： C12N15/1137 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/53 , C12Y301/01007 , C12N2310/3521
摘要： The invention relates to an antisense oligonucleotide targeted to the coding region of the human acetylcholinesterase (AChE), which selectively suppresses the AChE-R isoform of the enzyme. The antisense oligonucleotide is intended for use in the treatment and/or prevention of neuromuscular disorders, preferably myasthenia gravis. In addition, it can penetrate the blood-brain barrier (BBB) and destroy AChE-R within central nervous system neurons, while also serving as a carrier to transport molecules across the BBB.

12. 发明申请

US20060069051A1 AChE antisense oligonucleotide as an anti-inflammatory agent 审中-公开
公开(公告)号：US20060069051A1
公开(公告)日：2006-03-30
申请号：US11187719
申请日：2005-07-21
申请人： Hermona Soreq , Amir Dori , Itzhak Wirguin , Gal Ifergane , Raz Yirmiya
发明人： Hermona Soreq , Amir Dori , Itzhak Wirguin , Gal Ifergane , Raz Yirmiya
IPC分类号： A61K48/00
CPC分类号： A61K31/712 , A61K31/7088 , A61K48/00
摘要： Disclosed is a novel use for AChE antisense oligonucleotides as anti-inflammatory agents, wherein said oligonucleotides are preferably as denoted by SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:7. Methods of treatment of inflammatory conditions, as well as fever, and particularly inflammation-associated neuropathies such as Guillain-Barré Syndrome, are described.

13. 发明授权

US06258780B1 Method and composition for enabling passage through the blood-brain-barrier 失效
标题翻译：能够通过血脑屏障的方法和组成
公开(公告)号：US06258780B1
公开(公告)日：2001-07-10
申请号：US08975084
申请日：1997-11-20
申请人： Hermona Soreq , Alon Friedman , Shlomo Siedman , Daniela Kaufer
发明人： Hermona Soreq , Alon Friedman , Shlomo Siedman , Daniela Kaufer
IPC分类号： A61K3816
CPC分类号： C12Y301/01007 , A61K31/137 , A61K31/138 , A61K31/46 , A61K38/465 , A61K2300/00
摘要： A pharmaceutical composition for facilitating passage of compounds through the blood-brain barrier comprising the agent ACHE-I4 readthrough (SEQ ID No:1) splice variant or the I4 peptide (SEQ ID No:2) and analogues of each thereof and a pharmaceutically acceptable carrier is disclosed. Alternatively, the pharmaceutical composition for facilitating passage of compounds through the blood-brain barrier can comprise the agents adrenaline, atropine, dopamine and/or an adrenergic combination and a pharmaceutically acceptable carrier. The composition can comprise at least two of the agents. The composition of the present invention can optionally include the compound to be transported across the blood-brain barrier. Alternatively, the compound can be co-administered (simultaneously) with the composition or can be administered at some point during the biologically effective period of the action of the composition. The present invention provides a method for administering a compound to the CNS of an animal by subjecting the animal to a stress-mimicking agent or treatment. This agent or treatment facilitates disruption of the blood-brain barrier. During the period that the BBB is opened or disrupted a compound can be administer such that the compound is enabled to passage through the disrupted BBB into the CNS.
摘要翻译：一种用于促进化合物通过包含透明试剂ACHE-I4（SEQ ID No：1）剪接变体或I4肽（SEQ ID No：2）及其各自的类似物的药物组合物和药学上可接受的药物组合物载体被披露。或者，用于促进化合物通过血脑屏障的药物组合物可以包含肾上腺素，阿托品，多巴胺和/或肾上腺素能组合剂和药学上可接受的载体。所述组合物可包含至少两种所述试剂。本发明的组合物可以任选地包括待跨越血脑屏障转运的化合物。或者，化合物可以与组合物共同施用（同时），或者可以在组合物的作用的生物学有效期间的某一点施用。本发明提供了通过使动物经受应激模拟剂或治疗而将化合物给予动物的CNS的方法。该药剂或治疗有助于破坏血脑屏障。在BBB开放或中断期间，可以给予化合物使得化合物能够通过破坏的BBB进入CNS。

14. 发明授权

US6121046A Synthetic antisense oligodeoxynucleotides targeted to human ache 失效
标题翻译：靶向人类疼痛的合成反义寡脱氧核苷酸
公开(公告)号：US6121046A
公开(公告)日：2000-09-19
申请号：US990065
申请日：1997-12-12
申请人： Hermona Soreq , Shlomo Seidman , Fritz Eckstein , Alon Friedman , Daniela Kaufer
发明人： Hermona Soreq , Shlomo Seidman , Fritz Eckstein , Alon Friedman , Daniela Kaufer
IPC分类号： C12N15/09 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P25/00 , A61P43/00 , C12N20060101 , C12N15/113 , C12Q1/68 , C07H21/04 , C12N15/00
CPC分类号： C12Y301/01007 , C12N15/1137 , A01K2217/05 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/53
摘要： A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-ODN) capable of selectively modulating human acetylcholinesterase (AChE) production and a composition comprising at least one AS-ODN as an active ingredient. A nuclease resistant antisense targeted against the splice junction in the AChE mRNA post-splice message is disclosed. The synthetic nuclease resistant AS-ODNs are capable of selectively modulating human AChE production in the central nervous system or capable of selectively reducing human AChE deposition of the neuromuscular junction. The present invention also provides a method to restore balanced cholinergic signalling in the brain and spinal cord or reduce AChE in the neuromuscular junction in patients in need of such treatment by administering to a patient in need of such treatment a therapeutically effective amount of at least one of the synthetic nuclease resistant AS-ODN capable of selectively modulating human AChE production.
摘要翻译：能够选择性调节人乙酰胆碱酯酶（AChE）产生的合成核酸酶抗性反义寡脱氧核苷酸（AS-ODN）和包含至少一种AS-ODN作为活性成分的组合物。公开了针对针对AChE mRNA剪接信号中的剪接连接的核酸酶抗性反义。合成的核酸酶抗性AS-ODN能够选择性调节中枢神经系统中的人AChE产生或者能够选择性地降低神经肌肉接头的人类AChE沉积。本发明还提供了一种在需要这种治疗的患者中恢复脑和脊髓中的平衡胆碱能信号传导或减少神经肌肉接头中的AChE的方法，其通过向需要这种治疗的患者施用治疗有效量的至少一种的能够选择性调节人AChE生产的合成核酸酶抗性AS-ODN。

15. 发明申请

US20110136897A1 TOLL-LIKE RECEPTOR 9 AGONISTS FOR THE TREATMENT OF ANXIETY-RELATED DISORDERS AND INFLAMMATORY DISORDERS 审中-公开
标题翻译：类似感受器9的治疗放疗相关疾病和炎症性疾病的激素
公开(公告)号：US20110136897A1
公开(公告)日：2011-06-09
申请号：US13058876
申请日：2009-08-13
申请人： Hermona Soreq , Gabriel Zimmerman , Iftach Shaked
发明人： Hermona Soreq , Gabriel Zimmerman , Iftach Shaked
IPC分类号： A61K31/7084 , A61K31/56 , A61K31/7088
CPC分类号： C12N15/117 , A61K31/573 , A61K31/7084 , A61K45/06 , A61K48/00 , C12N2310/17 , C12N2310/321 , C12N2320/31 , A61K2300/00 , C12N2310/3521
摘要： Uses of TLR-9 agonists are disclosed. The uses include treatment of anxiety-related disorders and inflammatory disorders. For treatment of inflammatory disorders the TLR-9 agonists are administered together with a therapeutically effective amount of a glucocorticoid.
摘要翻译：公开了TLR-9激动剂的用途。用途包括治疗焦虑相关疾病和炎症性疾病。为了治疗炎症性疾病，TLR-9激动剂与治疗有效量的糖皮质激素一起施用。

16. 发明申请

US20070293452A1 Agents, compositions and methods for treating pathologies in which regulating an ache-associated biological pathway is beneficial 审中-公开
标题翻译：用于治疗其中调节与疼痛相关的生物学途径有利的病理学的药剂，组合物和方法
公开(公告)号：US20070293452A1
公开(公告)日：2007-12-20
申请号：US11808212
申请日：2007-06-07
申请人： Hermona Soreq , Iftach Shaked , Ran Avni , Ari Meerson
发明人： Hermona Soreq , Iftach Shaked , Ran Avni , Ari Meerson
IPC分类号： C12N5/08 , A61K31/7052 , A61P43/00 , C12Q1/68 , C07H19/00 , C12N15/00
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2310/321 , C12N2320/50 , C12N2310/3521
摘要： The present invention provides agents which are capable of regulating the function of a micro-RNA component which can be used to regulate an ACHE-associated biological pathway. In addition, the present invention provides methods and pharmaceutical compositions for the treatment of various pathologies related to AChE-associated biological pathways such as apoptosis, aberrant cholinergic signaling, abnormal hematopoietic proliferation and/or differentiation, cellular stress, exposure to inflammatory response-inducing agents, and/or exposure to organophosphates or other AChE inhibitors.
摘要翻译：本发明提供能够调节可用于调节ACHE相关生物学途径的微RNA组分的功能的试剂。此外，本发明提供了用于治疗与AChE相关生物学途径相关的各种病理学的方法和药物组合物，例如细胞凋亡，异常胆碱能信号传导，异常造血增生和/或分化，细胞应激，暴露于炎性反应诱导剂，和/或暴露于有机磷酸盐或其他AChE抑制剂。

17. 发明申请

US20060166204A1 Parkinson's disease susceptibility haptotype as a tool for genetic screening 审中-公开
标题翻译：帕金森病易感性结合型作为遗传筛选的工具
公开(公告)号：US20060166204A1
公开(公告)日：2006-07-27
申请号：US10529511
申请日：2003-09-24
申请人： Hermona Soreq , Liat Ben-Moyal , Boris Bryk , Alon Friedman
发明人： Hermona Soreq , Liat Ben-Moyal , Boris Bryk , Alon Friedman
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/156 , C12Q2600/172
摘要： Specific PON1 and ACHE alleles segregate in linkage, forming an haplotype which directly correlates with higher susceptibility to develop Parkinson's Disease (PD). This PD-susceptibility haplotype is herein presented as a tool for predicting the risk of developing Parkinson's Disease and its severity, both for an individual and for the population in general. Thus, the present invention provides the use of said PD-susceptibility haplotype in diagnostic and screening methods.
摘要翻译：特异性PON1和ACHE等位基因连锁分离，形成与更高易感性发展帕金森病（PD）直接相关的单倍型。这种PD-易感性单倍型在本文中被提供作为用于预测发展中的帕金森病的风险及其严重程度的工具，无论对于个人和一般人群来说。因此，本发明提供了所述PD-敏感性单元型在诊断和筛选方法中的用途。

18. 发明授权

US06326139B1 Method of screening for genetic predisposition to anticholinesterase therapy 失效
标题翻译：筛查抗胆碱酯酶治疗遗传易感性的方法
公开(公告)号：US06326139B1
公开(公告)日：2001-12-04
申请号：US08875710
申请日：1997-10-06
申请人： Hermona Soreq , Haim Zakut
发明人： Hermona Soreq , Haim Zakut
IPC分类号： C12Q168
CPC分类号： C12Q1/6883 , C12N9/18 , C12Q2600/156
摘要： A method of screening for a genetic predisposition to anticholinesterase exposure. The method includes the steps of obtaining a peripheral blood sample, and then analysing serum from the blood sample for BuChE levels and inhibitor-susceptibilities. The DNA of peripheral white blood cells from the blood sample is also screened for the presence of BuChE alleles thereby identifying patients who have a genetic predisposition to anticholinesterase exposure.
摘要翻译：筛选抗胆碱酯酶暴露的遗传易感性的方法。该方法包括获得外周血样品，然后分析血样中血清BuChE水平和抑制剂敏感性的步骤。还筛选来自血液样品的外周白细胞的DNA，以观察BuChE等位基因的存在，从而鉴定具有抗胆碱酯酶暴露的遗传易感性的患者。

19. 发明授权

US5932780A Transgenic non-human animal assay system for anti-cholinesterase substances 失效
标题翻译：用于抗胆碱酯酶物质的转基因非人动物测定系统
公开(公告)号：US5932780A
公开(公告)日：1999-08-03
申请号：US370156
申请日：1995-01-09
申请人： Hermona Soreq , Haim Zakut , Moshe Shani
发明人： Hermona Soreq , Haim Zakut , Moshe Shani
IPC分类号： C12N9/18 , C12N15/85 , C12Q1/46 , A01K67/00 , A01K67/027 , A01K67/033 , G01N33/00
CPC分类号： C12N15/8509 , A01K67/0278 , C12N9/18 , C12Q1/46 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2227/105 , A01K2227/50 , A01K2267/03 , A01K2267/0356
摘要： The present invention relates to novel alternative forms of human acetylcholinesterase (AChE) and nucleotide sequences encoding the same. The genes encoding the novel forms of human AChE have been identified in various malignant tumor cells. In a further aspect, the invention relates to a transgenic animal assay system for evaluating efficacy of drugs against cholinergic proteins, prior to or in the course of therapeutic treatment. Transgenic animals, preferably developing tadpole of Xenopus or mice which express human AChE, are used. The transgenic animal assay system is also useful for evaluating the toxicity of substances which potentially block human AChE (e.g. organophosphorous compounds).
摘要翻译：本发明涉及人乙酰胆碱酯酶（AChE）的新型替代形式及其编码的核苷酸序列。已经在各种恶性肿瘤细胞中鉴定了编码人类AChE的新型形式的基因。在另一方面，本发明涉及用于在治疗治疗之前或治疗过程中评价药物对胆碱能蛋白的功效的转基因动物测定系统。使用转基因动物，优选发育表达人AChE的非洲爪蟾的t us或小鼠。转基因动物测定系统也可用于评估可能阻断人类AChE（例如有机磷化合物）的物质的毒性。

20. 发明授权

US5891725A Synthetic antisense oligodeoxynucleotides and pharmaceutical compositions containing them 失效
标题翻译：合成的反义寡脱氧核苷酸和含有它们的药物组合物
公开(公告)号：US5891725A
公开(公告)日：1999-04-06
申请号：US318826
申请日：1994-12-01
申请人： Hermona Soreq , Haim Zakut , Fritz Eckstein
发明人： Hermona Soreq , Haim Zakut , Fritz Eckstein
IPC分类号： C12N15/09 , A61K31/70 , A61P35/00 , C07H21/04 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/1137 , C12Y301/01007 , C12Y301/01008 , C12N2310/111 , C12N2310/315
摘要： The invention relates to synthetic phosphorothioated or partially phosphorothioated oligodeoxynucleotides capable of selectively modulating hemopoietic bone marrow cells development. More particularly, the invention relates to synthetic antisense oligodeoxynucleotides directed against a region spanning the AUG initiation condon in human ACHE or 2HS genes, having phosphorothioate bonds linking between the nucleotide bases; synthetic antisense oligodeoxynucleotides directed against a region spanning the AUG initiation condon in human ACHE gene, 2HS gene or BCHE gene or against a 5'-region in the human CHED (cdc2 homolog) gene, having phosphorothioate bonds linking between the four 3'-terminus nucleotide bases. The invention also relates to pharmaceutical compositions comprising as active ingredient at least one synthetic phosphorothioated or partially phosphorothioated antisense oligodeoxynucleotides according to the invention in physiologically acceptable carrier in diluent. The antisense oligodeoxynucleotides of the invention and the pharmaceutical compositions containing them are suitable for inhibiting abnormal hemopoietic cells proliferation, inhibiting abnormal platelet proliferation, increasing stem cell fraction in bone marrow cell cultures, enhancing macrophage production and increasing stem cells counts, reducing immune response of organs to be transplanted, suppressing immune response of a recipient of an allotransplanted organ, and arresting growth of malignant tumors.
摘要翻译： PCT No.PCT / EP93 / 00911 Sec。 371 1994年12月1日第 102（e）1994年12月1日PCT PCT 1993年4月15日PCT公布。出版物WO93 / 21202 日期：1993年10月26日本发明涉及能够选择性调节造血骨髓细胞发育的合成硫代磷酸化或部分硫代磷酸化寡脱氧核苷酸。更具体地说，本发明涉及针对在ACHE或2HS基因中跨越AUG起始细胞周期的区域的合成的反义寡脱氧核苷酸，其具有在核苷酸碱基之间连接的硫代磷酸酯键; 针对跨越人类ACHE基因，2HS基因或BCHE基因中的AUG起始宽带的区域或针对人类CHED（cdc2同源基因）中的5'区域的合成的反义寡脱氧核苷酸，其具有连接在4个3'末端之间的硫代磷酸酯键核苷酸碱基。本发明还涉及包含根据本发明的至少一种合成的硫代磷酸化或部分硫代磷酸化的反义寡脱氧核苷酸作为活性成分的药物组合物，其在稀释剂中的生理学上可接受的载体中。本发明的反义寡脱氧核苷酸和含有它们的药物组合物适用于抑制异常造血细胞增殖，抑制异常血小板增殖，增加骨髓细胞培养物中的干细胞分数，增强巨噬细胞产生和增加干细胞计数，降低器官的免疫应答被移植，抑制同种异体移植器官的受体的免疫应答，并阻止恶性肿瘤的生长。

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