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：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。

公开(公告)号：US07063948B1

公开(公告)日：2006-06-20

申请号：US09980263

申请日：2000-05-31

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： G01N17/26 ,  C07K16/00 ,  C07K5/00

CPC分类号： C07K16/40 ,  G01N2800/2821

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：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：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。

公开(公告)号：US07456154B2

公开(公告)日：2008-11-25

申请号：US11346145

申请日：2006-02-01

申请人： Hermona Soreq ,  Jackilynne Seidman, legal representative ,  Tama Evron

发明人： Shlomo Seidman

IPC分类号： A61K31/70 ,  C07H21/02 ,  C07H21/04 ,  C12N5/00 ,  C12Q1/68

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。