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    Combinations of antisense oligonucleotides directed against thymidylate synthase mrna and uses thereof
    4.
    发明申请
    Combinations of antisense oligonucleotides directed against thymidylate synthase mrna and uses thereof 审中-公开
    针对胸苷酸合酶mrna的反义寡核苷酸的组合及其用途

    公开(公告)号：US20060135450A1

    公开(公告)日：2006-06-22

    申请号：US10510899

    申请日：2003-04-08

    申请人： D Koropatnick ,  Mark Vincent

    发明人： D Koropatnick ,  Mark Vincent

    IPC分类号： A61K48/00

    CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/315

    摘要： Effective combinations of antisense oligonucleotides directed against thymidylate synthase mRNA are provided for use in cancer therapies. Combinations of antisense oligonucleotides have enhanced activity compared to the activity of the individual antisense oligonucleotides when used alone. The combinations may be used in conjunction with one or more chemotherapeutic agents to enhance the effects of the chemotherapeutic(s). Such antisense oligonucleotide combinations constitute improved antisense therapies with application to a variety of cancers or proliferative disorders, including drug resistant cancers.

    摘要翻译： 提供针对胸苷酸合酶mRNA的反义寡核苷酸的有效组合用于癌症治疗。 当单独使用时，反义寡核苷酸的组合与单个反义寡核苷酸的活性相比具有增强的活性。 这些组合可以与一种或多种化学治疗剂结合使用以增强化学治疗剂的作用。 这样的反义寡核苷酸组合构成了可应用于多种癌症或增殖性疾病（包括耐药性癌症）的改进的反义治疗。

    Antisense oligonucleotides against thymidylate synthase
    5.
    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。

    ANTISENSE OLIGONUCLEOTIDE STRATEGIES FOR THE ENHANCEMENT OF CANCER THERAPIES
    8.
    发明申请
    ANTISENSE OLIGONUCLEOTIDE STRATEGIES FOR THE ENHANCEMENT OF CANCER THERAPIES 审中-公开
    用于增加癌症治疗的反义寡核苷酸战略

    公开(公告)号：US20080255066A1

    公开(公告)日：2008-10-16

    申请号：US12029297

    申请日：2008-02-11

    申请人： D. JAMES KOROPATNICK ,  Mark D. Vincent

    发明人： D. JAMES KOROPATNICK ,  Mark D. Vincent

    IPC分类号： A61K31/7105 ,  A61P35/00

    CPC分类号： C12N15/1137 ,  C12N2310/315

    摘要： Effective combinations of antisense agents directed against thymidylate synthase mRNA are provided for use in cancer therapies. Combinations of antisense agents have enhanced activity compared to the activity of the individual antisense agents when used alone. The combinations may be used in conjunction with one or more chemotherapeutic agents to enhance the effects of the chemotherapeutic(s). Such antisense agent combinations constitute improved antisense therapies with application to a variety of cancers or proliferative disorders, including drug resistant cancers.

    摘要翻译： 提供了针对胸苷酸合酶mRNA的反义剂的有效组合用于癌症治疗。 当单独使用时，反义剂的组合与单个反义剂的活性相比具有增强的活性。 这些组合可以与一种或多种化学治疗剂结合使用以增强化学治疗剂的作用。 这样的反义剂组合构成改进的反义治疗方法，其应用于各种癌症或增殖性疾病，包括耐药性癌症。