公开(公告)号：US20090281165A1

公开(公告)日：2009-11-12

申请号：US12287274

申请日：2008-10-07

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： A61K31/7088 ,  C07H21/04 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00

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.

摘要翻译： 本发明涉及靶向人乙酰胆碱酯酶（AChE）的编码区的反义寡核苷酸，其选择性地抑制酶的AChE-R同种型。 反义寡核苷酸旨在用于治疗和/或预防神经肌肉疾病，优选重症肌无力。 此外，它可以穿透血脑屏障（BBB），并破坏中枢神经系统神经元内的AChE-R，同时也可以作为跨越BBB传递分子的载体。

公开(公告)号：US07494783B2

公开(公告)日：2009-02-24

申请号：US11400224

申请日：2006-04-10

申请人： Hermona Soreq ,  Ella Sklan ,  Raz Yirmiya ,  Keren Ailon ,  Irit Shapira-Lichter

发明人： Hermona Soreq ,  Ella Sklan ,  Raz Yirmiya ,  Keren Ailon ,  Irit Shapira-Lichter

IPC分类号： C12Q1/46

CPC分类号： C12Q1/6883 ,  C12Q1/34 ,  C12Q1/46 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2600/172 ,  G01N33/573 ,  G01N2800/301

摘要： The invention provides methods/kits for assessing levels of trait or state anxiety in a subject by comparing genotypes and/or expression patterns at the ACHE, PON1 and/or BChE genes to the genotype and/or expression pattern of the genes in a reference population whose genotype and/or expression pattern of the genes is known or by correlating AChE levels activity to those of PON.

摘要翻译： 本发明提供了通过将ACHE，PON1和/或BChE基因的基因型和/或表达模式与参考群体中基因的基因型和/或表达模式进行比较来评估受试者的性状或状态焦虑水平的方法/试剂盒 其基因的基因型和/或表达模式是已知的或通过将AChE水平活性与PON的活性相关联。

公开(公告)号：US20070065882A1

公开(公告)日：2007-03-22

申请号：US11401670

申请日：2006-04-11

申请人： Hermona Soreq ,  Amiram Eldor ,  Sofia Eldor ,  Varda Deutsch ,  Dan Grisaru

发明人： Hermona Soreq ,  Amiram Eldor ,  Sofia Eldor ,  Varda Deutsch ,  Dan Grisaru

IPC分类号： G01N33/567 ,  C07K16/40

CPC分类号： C07K16/40 ,  A61K38/00 ,  C07K2319/00 ,  C12N9/18

摘要： The invention relates to a cell growth and/or differentiation regulatory peptide comprising a sequence of about 9 to about 150 amino acids derived from acetylcholinesterase amino acid sequence, preferably from the C-terminal region of acetylcholinesterase. The invention also relates to pharmaceutical compositions comprising the peptides, particularly for use in promoting survival of stem cells, promoting differentiation of stem cells, promoting growth of stem cells and/or promoting the growth-enhancing effect of a growth factor on stem cells, alone, or in combination with other growth factors. Of particular interest is the use of the peptides in the treatment of thrombocytopenia, post-irradiation conditions, post-chemotherapy conditions, or conditions following massive blood loss and promotion of neural progenitors in use for cell therapies aimed at restoring neural functions in diseased individuals. Further, the invention relates to antibodies against the peptides, inter alia for diagnostic use, for example, the diagnosis of stress-induced male infertility. The invention also relates to in vitro and in vivo methods for screening of drugs that affect the central nervous system, and are potential modulators of interactions between the “readthrough” form of acetylcholinesterase, AChE-R, the intracellular receptor RACK1 and the kinase PKC.

摘要翻译： 本发明涉及包含衍生自乙酰胆碱酯酶氨基酸序列的约9至约150个氨基酸序列的细胞生长和/或分化调节肽，优选来自乙酰胆碱酯酶的C-末端区。 本发明还涉及包含这些肽的药物组合物，特别是用于促进干细胞的存活，促进干细胞的分化，促进干细胞的生长和/或促进生长因子对干细胞的生长增强作用 ，或与其他生长因子结合使用。 特别感兴趣的是在治疗血小板减少症，照射后条件，化疗后条件或大量失血后的病症中使用肽，并促进神经祖细胞在用于恢复患病个体的神经功能的细胞疗法中。 此外，本发明涉及针对肽的抗体，特别是用于诊断用途，例如应激诱导的男性不育症的诊断。 本发明还涉及用于筛选影响中枢神经系统的药物的体外和体内方法，并且是“阅读”形式的乙酰胆碱酯酶，AChE-R，细胞内受体RACK1和激酶PKC之间的相互作用的潜在调节剂。

公开(公告)号：US20060121536A1

公开(公告)日：2006-06-08

申请号：US11352073

申请日：2006-02-10

申请人： Hermona Soreq ,  Daniela Kaufer ,  Alon Friedman ,  Shlomo Seidman

发明人： Hermona Soreq ,  Daniela Kaufer ,  Alon Friedman ,  Shlomo Seidman

IPC分类号： G01N33/53 ,  C07K16/40

CPC分类号： C07K16/40 ,  G01N33/6896 ,  G01N2333/918

摘要： The invention relates to antibodies recognizing acetylcholinesterase or a C-terminal peptide derived from acetyl-cholinesterase, useful in diagnosing central nervous system (CNS) stress, elevated glucocorticoid level, disruption of the blood-brain barrier or Alzheimer's disease. The invention also relates to methods for the diagnosis of central nervous system (CNS) stress, elevated glucocorticoid level or disruption of the blood-brain barrier in a mammal, by use of the antibodies of the invention.

摘要翻译： 本发明涉及可用于诊断中枢神经系统（CNS）应激，升高的糖皮质激素水平，血脑屏障或阿尔茨海默氏病破坏的乙酰胆碱酯酶或源自乙酰胆碱酯酶的C-末端肽的抗体。 本发明还涉及通过使用本发明的抗体诊断中枢神经系统（CNS）应激，升高的糖皮质激素水平或哺乳动物血脑屏障破坏的方法。

公开(公告)号：US06475998B1

公开(公告)日：2002-11-05

申请号：US09380532

申请日：1999-11-12

申请人： Hermona Soreq ,  Shlomo Seidman ,  Esther Shohami

发明人： Hermona Soreq ,  Shlomo Seidman ,  Esther Shohami

IPC分类号： A61K4800

CPC分类号： C12N15/1137 ,  A61K31/137 ,  A61K31/138 ,  A61K38/00 ,  C12N2310/111

摘要： The invention provides methods and pharmaceutical compositions thereof for treating injury to the central nervous system (CNS). The method includes administering to the CNS of a patient suffering from such an injury a therapeutically effective amount of an inhibitor of acetylcholinesterase (AChE) production immediately following the injury. The methods use as the inhibitor a synthetic nuclease resistant antisense oligonucleotide or ribozyme that is directed against an accessible domain of the AChE mRNA brain variant. The treatment downregulates AChE production and thereby activity. The injury to the CNS may be a head injury (closed or open), brain injury, or spinal cord trauma or other trauma to the CNS.

摘要翻译： 本发明提供了用于治疗对中枢神经系统（CNS）的损伤的方法和药物组合物。 该方法包括向患有这种损伤的患者的CNS施用治疗有效量的紧邻损伤后的乙酰胆碱酯酶（AChE）抑制剂。 该方法用作抑制剂，其是针对AChE mRNA脑变体的可接近结构域的合成核酸酶抗性反义寡核苷酸或核酶。 治疗下调AChE生产，从而降低活动。 中枢神经系统的损伤可能是脑损伤（闭合或开放），脑损伤或脊髓创伤或CNS的其他创伤。

公开(公告)号：US6110742A

公开(公告)日：2000-08-29

申请号：US850347

申请日：1997-05-02

申请人： Hermona Soreq ,  Shlomo Seidman ,  Fritz Eckstein

发明人： Hermona Soreq ,  Shlomo Seidman ,  Fritz Eckstein

IPC分类号： A61K31/137 ,  A61K31/138 ,  A61K31/46 ,  A61K38/00 ,  A61K38/46 ,  C12N15/113 ,  C07H21/04 ,  A61K48/00 ,  C12N15/00 ,  C12Q1/68

CPC分类号： C12N15/1137 ,  A61K31/137 ,  A61K31/138 ,  A61K31/46 ,  C12Y301/01007 ,  C12Y301/01008 ,  A01K2217/05 ,  C12N2310/111 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/53

摘要： A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-OND) capable of selectively modulating human acetylcholinesterase production in the central nervous system is provided. In an embodiment the antisense oligodeoxynucleotide can be selected from5'ACGCTTTCTTGAGGC 3' SEQ ID No:1, or - 5'GGCACCCTGGGCAGC 3' SEQ ID No:2. The present invention also discloses a pharmaceutical or medical composition comprising as active ingredient at least one synthetic nuclease resistant antisense oligodeoxynucleotide capable of selectively modulating human acetylcholinesterase production in the central nervous system in a physiologically acceptable carrier or diluent. The present invention also provides a method to restore balanced cholinergic signaling in the brain in patients in need of such treatment comprising administering to a patient in need of such treatment a therapeutically effective amount of at least one of a synthetic nuclease resistant antisense oligodeoxynucleotide capable of selectively modulating human acetylcholinesterase production in the central nervous system in a physiologically acceptable carrier.

摘要翻译： 提供了能够选择性调节中枢神经系统中的人乙酰胆碱酯酶生成的合成核酸酶抗性反义寡脱氧核苷酸（AS-OND）。 在一个实施方案中，反义寡脱氧核苷酸可以选自5'ACGCTTTCTTGAGGC 3'SEQ ID No：1或 - - 5'GGCACCCTGGGCAGC 3'SEQ ID No：2。 - 本发明还公开了一种药物或医药组合物，其包含至少一种能够在生理上可接受的载体或稀释剂中在中枢神经系统中选择性调节人乙酰胆碱酯酶产生的合成核酸酶抗性反义寡脱氧核苷酸作为活性成分。 本发明还提供一种在需要这种治疗的患者中恢复脑中平衡胆碱能信号传导的方法，包括向需要这种治疗的患者施用治疗有效量的至少一种能够选择性地合成核酸酶抗性反义寡脱氧核苷酸 在生理上可接受的载体中调节中枢神经系统中的人乙酰胆碱酯酶的产生。