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    ANTISENSE OLIGONUCLEOTIDE COMPOSITIONS AND METHODS FOR THE MODULATION OF JNK PROTEINS
    25.
    发明申请
    ANTISENSE OLIGONUCLEOTIDE COMPOSITIONS AND METHODS FOR THE MODULATION OF JNK PROTEINS 审中-公开
    抗生素寡核苷酸组合物和调节JNK蛋白的方法

    公开(公告)号：US20070149472A1

    公开(公告)日：2007-06-28

    申请号：US11567631

    申请日：2006-12-06

    申请人： Robert McKay ,  Nicholas Dean

    发明人： Robert McKay ,  Nicholas Dean

    IPC分类号： A61K48/00 ,  C07H21/04

    CPC分类号： C12N15/1137 ,  C12N2310/11

    摘要： Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. Methods for inducing apoptosis and for treating diseases or conditions associated with a reduction in apoptosis are also provided.

    摘要翻译： 提供了通过调节编码JunN末端激酶（JNK蛋白）的基因的表达进行治疗的疾病或病症的治疗和诊断的组合物和方法。 本文提供了与编码JNK1，JNK2和JNK3的核酸以及其它JNK蛋白及其特异性同种型特异性杂交的寡核苷酸。 还提供了通过用这种寡核苷酸调节一种或多种JNK蛋白质的表达来治疗患有治疗性干预的疾病或障碍的动物的方法。 还提供了用于治疗和诊断与一种或多种JNK蛋白异常表达相关的疾病或病症的方法。 还提供了用于诱导凋亡和用于治疗与凋亡降低相关的疾病或病症的方法。

    Antisense oligonucleotides against thymidylate synthase
    29.
    发明申请
    Antisense oligonucleotides against thymidylate synthase 审中-公开
    针对胸苷酸合酶的反义寡核苷酸

    公开(公告)号：US20050272683A1

    公开(公告)日：2005-12-08

    申请号：US11171435

    申请日：2005-07-01

    申请人： Donald Koropatnick ,  Mark Vincent ,  Nicholas Dean

    发明人： Donald Koropatnick ,  Mark Vincent ,  Nicholas Dean

    IPC分类号： C12N15/09 ,  A61K31/7088 ,  A61K38/00 ,  A61K48/00 ,  A61P35/00 ,  A61P43/00 ,  C12N9/10 ,  C12N15/113 ,  A61K31/522 ,  C07H21/02

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

    摘要： Antisene oligonucleotides targeted to sequences in thymidylate synthase (TS) mRNA. In particular the invention relates to antisense oligonucleotides targeted to sequences in the 3′ end of TS mRNA, which are both cytostatic on their own when administered to human tumour cell lines, and which also enhance the toxicity of anticancer drugs such as Tomudex. The invention also relates to antisense oligonucleotides targeted to sequences at or near the translation start site at the 5′ end of TS mRNA which induce TS gene transcription and enhance cell growth. The invention further relates to a combination product comprising an antisense oligonucleotide in combination with an anticancer agent such as Tomudex (N-(5[N-3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl)-L-glutamic acid) or the Zeneca development compound ZD 9331 ((S)-2-(2-fluoro-4-[N-(4-hydroxy-2,7-dimethylquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino] benzamido-4-(1H-1,2,3,4-tetrazol-5-yl) butyric acid), and to the use of such a combination product in the treatment of cancer.

    摘要翻译： 靶向胸苷酸合酶（TS）mRNA序列的反义寡核苷酸。 特别地，本发明涉及靶向TS mRNA的3'端的序列的反义寡核苷酸，当被给予人肿瘤细胞系时它们本身都是细胞抑制的，并且还增强抗肿瘤药物如Tomudex的毒性。 本发明还涉及针对诱导TS基因转录并增强细胞生长的TS mRNA的5'末端的翻译起始位点处或附近的序列的反义寡核苷酸。 本发明还涉及包含反义寡核苷酸与抗癌剂如Tomudex（N-（5-N，3,4-二氢-2-甲基-4-氧代喹唑啉-6-基甲基）-N- 甲基氨基] -2-噻吩甲酰基）-L-谷氨酸）或Zeneca显影化合物ZD 9331（（S）-2-（2-氟-4- [N-（4-羟基-2,7-二甲基喹唑啉-6-基） 吡啶-2-基甲基）-N-（丙-2-炔基）氨基]苯甲酰氨基-4-（1H-1,2,3,4-四唑-5-基）丁酸），以及这种组合产物在 治疗癌症。