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    METHODS AND COMPOSITIONS FOR PAIN MANAGEMENT
    4.
    发明申请
    METHODS AND COMPOSITIONS FOR PAIN MANAGEMENT 审中-公开
    疼痛管理方法与组成

    公开(公告)号：WO00031290A1

    公开(公告)日：2000-06-02

    申请号：PCT/US1999/027582

    申请日：1999-11-22

    IPC: A61K38/46 ,  C12Q1/46 ,  G01N33/52 ,  G01N33/94

    CPC classification number: G01N33/523 ,  A61K38/465 ,  C12Q1/46 ,  C12Q2334/30 ,  C12Q2334/70 ,  C12Y301/01007 ,  G01N33/9406 ,  G01N33/944 ,  G01N2800/52 ,  Y10S435/975

    Abstract: The present invention provides novel methods and diagnostic kits for the objective measurement of the severity of pain or stress being experienced by a patient with a disorder, diagnosis and treatment for patients suffering from painful disorders, and monitoring the effectiveness of different pain-treatment protocols. Pain-measuring methods comprise collecting a sample from a patient and determining the presence of a pain-associated marker in the sample. Methods for alleviating pain comprise administrating a dose of a therapeutically effective amount of a composition to the patient wherein the dose is determined by the presence of a pain-associated marker in a biological sample obtained from the patient. Compositions for alleviating pain comprise substances that are pain-associated markers or agents that interfere with pain-associated markers, and block or modulate the progression of pain perceived by the patient.

    Abstract translation: 本发明提供了用于客观测量患有疼痛病症的患者的病症，诊断和治疗的患者经历的疼痛或压力的严重程度以及监测不同疼痛治疗方案的有效性的新型方法和诊断试剂盒。 疼痛测量方法包括从患者收集样品并确定样品中疼痛相关标志物的存在。 减轻疼痛的方法包括向患者施用治疗有效量的组合物的剂量，其中通过在从患者获得的生物样品中存在疼痛相关标志物来确定剂量。 用于缓解疼痛的组合物包括与疼痛相关的标志物或干扰疼痛相关标志物的试剂以及阻断或调节患者感觉到的疼痛进展的物质。

    SYNTHETIC ANTISENSE OLIGODEOXYNUCLEOTIDES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
    5.
    发明申请
    SYNTHETIC ANTISENSE OLIGODEOXYNUCLEOTIDES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM 审中-公开
    合成抗体寡糖氧化酶和含有它们的药物组合物

    公开(公告)号：WO1998026062A2

    公开(公告)日：1998-06-18

    申请号：PCT/US1997023598

    申请日：1997-12-12

    Applicant: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM ,  KOHN, Kenneth, I. ,  SOREQ, Hermona ,  SEIDMAN, Shlomo ,  ECKSTEIN, Fritz ,  FRIEDMAN, Alon ,  KAUFER, Daniela

    Inventor： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM ,  KOHN, Kenneth, I.

    IPC: C12N15/00

    CPC classification number: C12Y301/01007 ,  A01K2217/05 ,  A61K38/00 ,  C12N15/1137 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/53 ,  C12N2310/3521

    Abstract: A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-ODN) capable of selectively modulating human acetylcholinesterase (AChE) production and a pharmaceutical or medical composition comprising at least one AD-ODN as an active ingredient. In an embodiment the AS-ODN can be selected from 5'ACGCTTTCTTGAGGC 3' (SEQ ID NO.1), 5'GGCACCCTGGGCAGC 3' (SEQ ID NO.2); 5'CCACGTCCTCCTGCACCGTC 3' (SEQ ID NO.6); 5'ATGAACTCGATCTCGTAGCC 3' (SEQ ID NO.7); 5'GCCAGAGGAGGAGGAGAAGG 3' (SEQ ID NO.4); 5'TAGCGTCTACCACCCCTGAC 3' (SEQ ID NO.5), 5'TCTGTGTTATAGCCCAGCCC 3' (SEQ ID NO.17); and 5'GGCCTGTAACAGTTTATTT 3' (SEQ ID NO.18). A nuclease resistant antisense targeted against the splice junction in the AChEmRNA post splice message is disclosed. In an embodiment, a nuclease resistant AS-ODN targeted against the E4-E6 junction in the E1-E4-E6 splice variant AChEmRNA is disclosed as being highly specific for the muscle and central nervous system splice variant of AChE. 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 in the neuromuscular junction. The present invention also provides a method to restore balanced cholinergic signaling in the brain and spinal cord or reduce AChE in the neuromuscular junction 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 the synthetic nuclease resistant AS-ODN capable of selectively modulating human AChE production.

    Abstract translation: 能够选择性调节人乙酰胆碱酯酶（AChE）生产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AD-​​ODN作为活性成分的药物或医药组合物。 在一个实施方案中，AS-ODN可以选自5'ACGCTTTCTTGAGGC 3'（SEQ ID NO.1），5'GGCACCCTGGGCAGC 3'（SEQ ID NO.2）; 5'CCACGTCCTCCTGCACCGTC 3'（SEQ ID NO.6）; 5'ATGAACTCGATCTCGTAGCC 3'（SEQ ID NO.7）; 5'GCCAGAGGAGGAGGAGAAGG 3'（SEQ ID NO.4）; 5'TAGCGTCTACCACCCCTGAC 3'（SEQ ID NO.5），5'TCTGTGTTATAGCCCAGCCC 3'（SEQ ID NO.17）; 和5'GGCCTGTAACAGTTTATTT 3'（SEQ ID NO.18）。 公开了针对针对AChEmRNA后剪接消息中的剪接连接的核酸酶抗性反义。 在一个实施方案中，公开了针对E1-E4-E6剪接变体AChEmRNA中的E4-E6连接的核酸酶抗性AS-ODN作为AChE的肌肉和中枢神经系统剪接变体的高度特异性。 合成的核酸酶抗性AS-ODNs能够选择性调节中枢神经系统中的人AChE产生或能够选择性地降低神经肌肉接头中的人类AChE沉积。 本发明还提供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，包括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。

    UNIFORMLY CONJUGATED SERINE HYDROLASES
    7.
    发明申请
    UNIFORMLY CONJUGATED SERINE HYDROLASES 审中-公开
    均匀的丝氨酸水解酶

    公开(公告)号：WO2006137052A3

    公开(公告)日：2007-03-01

    申请号：PCT/IL2006000669

    申请日：2006-06-08

    Applicant: ISRAEL STATE ,  COHEN OFER ,  KRONMAN CHANOCH ,  VELAN BARUCH ,  SHAFFERMAN AVIGDOR

    Inventor： COHEN OFER ,  KRONMAN CHANOCH ,  VELAN BARUCH ,  SHAFFERMAN AVIGDOR

    IPC: G01N33/53

    CPC classification number: C12N9/18 ,  A61K47/60 ,  C12Y301/01007

    Abstract: An organophosphate scavenger is provided, with extended residence time in the mammalian circulation, which can be used in preventive and therapeutic treatment of organophosphate poisoning. The scavenger is a uniformly pegylated serine hydrolase, in which a part of lysine residues were replaced with other residues by site-directed mutagenesis. One part of lysine residues in the hydrolase amino acid sequence is selected for the PEG-coupling, and the other part for the replacement, wherein the selection should ensure that the hydrolase surface shows at least one free amino acid for PEG coupling for all possible views obtained by rotating a 3-D model generated for the hydrolase.

    Abstract translation: 提供了有机磷酸盐清除剂，其在哺乳动物循环中具有延长的停留时间，其可用于预防和治疗有机磷酸盐中毒。 清除剂是均匀聚乙二醇化的丝氨酸水解酶，其中一部分赖氨酸残基被其他残基替代，通过定点诱变。 选择水解酶氨基酸序列中赖氨酸残基的一部分用于PEG偶联，另一部分用于替换，其中选择应确保水解酶表面显示至少一种用于所有可能视图的PEG偶联的游离氨基酸 通过旋转为水解酶产生的3-D模型获得。

    A METHOD AND COMPOSITION FOR ENABLING PASSAGE THROUGH THE BLOOD-BRAIN BARRIER
    10.
    发明申请
    A METHOD AND COMPOSITION FOR ENABLING PASSAGE THROUGH THE BLOOD-BRAIN BARRIER 审中-公开
    通过血脑屏障通气的方法和组合物

    公开(公告)号：WO1998022132A1

    公开(公告)日：1998-05-28

    申请号：PCT/US1997021696

    申请日：1997-11-20

    Applicant: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM ,  KOHN, Kenneth, I. ,  SOREQ, Hermona ,  FRIEDMAN, Alon ,  SEIDMAN, Shlomo ,  KAUFER, Daniela

    Inventor： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM ,  KOHN, Kenneth, I.

    IPC: A61K38/46

    CPC classification number: C12Y301/01007 ,  A61K31/137 ,  A61K31/138 ,  A61K31/46 ,  A61K38/465 ,  A61K2300/00

    Abstract: 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 administered such that the compound is enabled to pass through the disrupted BBB into the CNS.

    Abstract translation: 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开放或破坏的时期期间，化合物可以被施用使得化合物能够通过破坏的BBB进入CNS。

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