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    Antisense oligonucleotides directed to genes regulated by trapoxin-induced HDAC inhibition
    1.
    发明申请
    Antisense oligonucleotides directed to genes regulated by trapoxin-induced HDAC inhibition 审中-公开
    针对由诱毒蛋白诱导的HDAC抑制调节的基因的反义寡核苷酸

    公开(公告)号：US20060040884A1

    公开(公告)日：2006-02-23

    申请号：US11191875

    申请日：2005-07-28

    申请人： Francis Buxton ,  Dalia Cohen ,  Denise Fischer ,  Shaowen Wang

    发明人： Francis Buxton ,  Dalia Cohen ,  Denise Fischer ,  Shaowen Wang

    IPC分类号： A61K48/00 ,  C07H21/04

    CPC分类号： C12N15/1137 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Y203/01048 ,  G01N2333/91057 ,  C12N2310/3525

    摘要： Antisense compounds, compositions and methods are provided for modulating the expression of trapoxin A regulated genes, including but not limited to those genes induced by ectopic expression of p21waf1 that are disclosed herein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding these genes. Methods of using these compounds for modulation of expression of these genes and for treatment of diseases associated with these genes, as well as those associated with abnormal HDAC activity, particularly cancer or others characterized by abnormal cell proliferation, are provided. Furthermore, the invention relates to the use of RhoB as a biomarker to evaluate the efficacy of treatment of humans with abnormal HDAC activity including proliferative diseases such as cancer. Also disclosed is a method for identifying HDAC inhibitors and trapoxin analogs based on the surprising discovery that up regulation or RhoB and increased RhoB protein levels are associated with HDAC inhibition.

    摘要翻译： 提供反义化合物，组合物和方法用于调节调节蛋白A调节的基因的表达，包括但不限于本文公开的由p21 的异位表达诱导的那些基因。 组合物包含靶向编码这些基因的核酸的反义化合物，特别是反义寡核苷酸。 提供了使用这些化合物调节这些基因的表达和治疗与这些基因有关的疾病的方法，以及与异常HDAC活性相关的疾病，特别是癌症或以异常细胞增殖为特征的其他方法。 此外，本发明涉及RhoB作为生物标志物的用途，以评估治疗具有异常HDAC活性的人的功效，包括增殖性疾病如癌症。 还公开了基于令人惊讶的发现，鉴定HDAC抑制剂和诱导蛋白类似物的方法，即上调或RhoB和增加的RhoB蛋白水平与HDAC抑制相关。

    Methods for the treatment of chronic pain and compositions therefor
    3.
    发明申请
    Methods for the treatment of chronic pain and compositions therefor 审中-公开
    治疗慢性疼痛及其组合物的方法

    公开(公告)号：US20070129366A1

    公开(公告)日：2007-06-07

    申请号：US11644658

    申请日：2006-12-22

    申请人： Francis Buxton ,  Pamposh Ganju ,  Christopher Snell ,  Chuanzheng Song

    发明人： Francis Buxton ,  Pamposh Ganju ,  Christopher Snell ,  Chuanzheng Song

    IPC分类号： A61K31/5375 ,  A61K31/519

    CPC分类号： A61K31/70 ,  A61K31/00 ,  A61K31/519 ,  A61K31/5375 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/711 ,  A61K2039/505 ,  C12Q1/37 ,  G01N2500/04

    摘要： The invention discloses cathepsin S as a suitable target for the development of new therapeutics to treat or ameliorate chronic pain. The invention relates to methods to treat and/or ameliorate chronic pain and pharmaceutical compositions therefor comprising modulators with inhibitory effect on cathepsin S enzyme activity and/or cathepsin S gene expression. The invention also relates to a method to identify compounds with therapeutic usefulness to treat chronic pain, comprising identifying compounds that can inhibit cathepsin S activity and/or gene expression which can also reverse the pathological effects of chronic pain in vivo.

    摘要翻译： 本发明公开了组织蛋白酶S作为开发用于治疗或改善慢性疼痛的新治疗剂的合适靶标。 本发明涉及治疗和/或改善慢性疼痛的方法及其药物组合物，其包含对组织蛋白酶S酶活性和/或组织蛋白酶S基因表达具有抑制作用的调节剂。 本发明还涉及鉴定具有治疗慢性疼痛的治疗有用性的化合物的方法，其包括鉴定能够抑制组织蛋白酶S活性和/或基因表达的化合物，其还可逆转慢性疼痛在体内的病理作用。

    Methods for diagnosing and treating schizophrenia
    4.
    发明申请
    Methods for diagnosing and treating schizophrenia 审中-公开
    诊断和治疗精神分裂症的方法

    公开(公告)号：US20070015152A1

    公开(公告)日：2007-01-18

    申请号：US10538339

    申请日：2003-12-11

    申请人： Francis Buxton ,  William Carpenter ,  Rosalinda Roberts ,  Carol Tamminga

    发明人： Francis Buxton ,  William Carpenter ,  Rosalinda Roberts ,  Carol Tamminga

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6883 ,  C12Q2600/158

    摘要： The genes encoding SCYA2, GADD45B, S100A8, CDKN1A, IL1RL1, TGM2, MAFF, SERPINA3, GRO1, CD14, KIAA1075, CHI3L1, SERPINH1, MT1X, KIAA0620, TIMP1, NUMA1, DDIT3 and TOB2, are upregulated in the anterior cingulate of schizophrenic patients compared to normal patients and as such are useful drug targets for schizophrenia. Methods of screening, diagnosing and treating schizophrenia based on these genes are provided. Transgenic nonhuman animals having increased copy number or increased expression levels of these genes are also provided. The transgenic nonhuman animals are used in methods for screening for potential therapeutic agents.

    摘要翻译： 在精神分裂症患者的前扣带上编码SCYA2，GADD45B，S100A8，CDKN1A，IL1RL1，TGM2，MAFF，SERPINA3，GRO1，CD14，KIAA1075，CHI3L1，SERPINH1，MT1X，KIAA0620，TIMP1，NUMA1，DDIT3和TOB2的基因 与正常患者相比，因此是精神分裂症的有用药物靶点。 提供了基于这些基因的筛选，诊断和治疗精神分裂症的方法。 还提供了具有增加的这些基因的拷贝数或增加的表达水平的转基因非人动物。 转基因非人动物用于筛选潜在治疗剂的方法中。