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    LNA oligonucleotides and the treatment of cancer
    1.
    发明授权
    LNA oligonucleotides and the treatment of cancer 失效
    LNA寡核苷酸和癌症的治疗

    公开(公告)号：US08173428B2

    公开(公告)日：2012-05-08

    申请号：US12249676

    申请日：2008-10-10

    申请人： Christoph Rosenbohm ,  Lene Sonderbye Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens Bo Hansen ,  Marlene Asklund

    发明人： Christoph Rosenbohm ,  Lene Sonderbye Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens Bo Hansen ,  Marlene Asklund

    IPC分类号： C12N15/00 ,  C12N5/00 ,  C07H21/04

    CPC分类号： C12N15/1135 ,  A61K38/00 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/319 ,  C12N2310/3341

    摘要： The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5′-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx(Gx)(c)-3′, and preferably of the general formula 5′-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3′, wherein capital letters designate an LNA nucleotide analogue selected from β-D-oxy-LNA, β-D-thio-LNA, β-D-amino-LNA and α-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumor development in vivo. The LNA oligonucleotides are superior to other LNA oligonucleotides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.

    摘要翻译： 本公开涉及具有通式5' - （MeC x）（Tx）MeC x As A stscscsastsgsgsMeC x A x（G x）（c）-3'的（亚）序列的LNA寡核苷酸，优选通式为5'-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3' 其中大写字母表示选自以下的LNA核苷酸类似物：-D-oxy-LNA，＆bgr; -D-thio-LNA，＆bgr; -D-氨基-LNA和α-L-氧-LNA，小字母表示脱氧核苷酸 ，下划线表示如上定义的LNA核苷酸类似物或脱氧核苷酸。 这样的LNA寡核苷酸在通过反义机制抑制存活蛋白的表现方面表现出惊人的良好性质，从而导致体内肿瘤发展的减少或抑制。 LNA寡核苷酸优于靶向通过功能读数如凋亡诱导和增殖抑制测定的存活mRNA的其他LNA寡核苷酸，并且在转染的癌细胞系中下调存活蛋白mRNA和蛋白质的有效性，并且与紫杉醇优良结合诱导凋亡 与其他LNA寡核苷酸相比。

    LNA OLIGONUCLEOTIDES AND THE TREATMENT OF CANCER
    2.
    发明申请
    LNA OLIGONUCLEOTIDES AND THE TREATMENT OF CANCER 审中-公开
    LNA OLIGONUCLEOTIDES AND THE ACCEATMENT OF CANCER

    公开(公告)号：US20120322848A1

    公开(公告)日：2012-12-20

    申请号：US13443557

    申请日：2012-04-10

    申请人： Christoph Rosenbohm ,  Lene S. Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens B. Hansen ,  Marlene Asklund

    发明人： Christoph Rosenbohm ,  Lene S. Kjaerulff ,  Majken Westergaard ,  Margit Wissenbach ,  Jens B. Hansen ,  Marlene Asklund

    IPC分类号： A61K31/712 ,  A61P35/02 ,  A61P35/00

    CPC分类号： C12N15/1135 ,  A61K38/00 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/319 ,  C12N2310/3341

    摘要： The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5′-(MeCx)(Tx)MeCxAsAstsCsCsastsgsgsMeCxAx(Gx)(c)-3′, and preferably of the general formula 5′-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3′, wherein capital letters designate an LNA nucleotide analogue selected from β-D-oxy-LNA, β-D-thio-LNA, β-D-amino-LNA and α-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumour development in vivo. The LNA oligonucleotides are superior to other LNA oligonucletides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.

    摘要翻译： 本公开内容涉及具有通式5'（（MeCx）（Tx）MeCxAsAstsCsCsastsgsgsMeCxAx（Gx）（c）-3'，优选通式为5'-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3'的（亚）序列的LNA寡核苷酸， 其中大写字母表示选自以下的LNA核苷酸类似物：-D-oxy-LNA，＆bgr; -D-thio-LNA，＆bgr; -D-氨基-LNA和α-L-氧-LNA，小字母表示脱氧核苷酸 ，下划线表示如上定义的LNA核苷酸类似物或脱氧核苷酸。 这样的LNA寡核苷酸在通过反义机制抑制存活蛋白的表现方面表现出惊人的良好性质，从而导致体内肿瘤发展的减少或抑制。 LNA寡核苷酸优于靶向通过功能读数（如凋亡诱导和增殖抑制）测量的存活mRNA的其他LNA寡核苷酸，并且在转染的癌细胞系中下调Survivin mRNA和蛋白质，并且与Taxol优异结合诱导凋亡有效 与其他LNA寡核苷酸相比。

    RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-B100 EXPRESSION
    6.
    发明申请
    RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-B100 EXPRESSION 审中-公开
    用于抑制APO-B100表达的RNA拮抗剂化合物

    公开(公告)号：US20090118213A1

    公开(公告)日：2009-05-07

    申请号：US12066852

    申请日：2006-09-01

    申请人： Henrik Frydenlund Hansen ,  Bo Hansen ,  Majken Westergaard ,  Ellen Marie Straarup ,  Christoph Rosenbohm

    发明人： Henrik Frydenlund Hansen ,  Bo Hansen ,  Majken Westergaard ,  Ellen Marie Straarup ,  Christoph Rosenbohm

    IPC分类号： A61K31/7088 ,  C07H21/04

    CPC分类号： C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3515

    摘要： Oligonucleotides directed against the Apo-B100 gene are provided for modulating the expression of Apo-B100. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Apo-B100. Methods of using these compounds for modulation of Apo-B100 expression and for the treatment of diseases associated with either overexpression of Apo-B100, expression of mutated Apo-B100 or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

    摘要翻译： 提供针对Apo-B100基因的寡核苷酸用于调节Apo-B100的表达。 组合物包含针对编码Apo-B100的核酸的寡核苷酸，特别是反义寡核苷酸。 提供了使用这些化合物调节Apo-B100表达和治疗与Apo-B100的过度表达相关的疾病，突变的Apo-B100或两者的表达的方法。 疾病的例子包括肺，乳腺，结肠，前列腺，胰腺，肺，肝，甲状腺，肾，脑，睾丸，胃，肠，肠，脊髓，鼻窦，膀胱，尿道或卵巢癌等癌症。 寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁定的核酸或其组合构成。

    Adenosine Receptor Antagonists
    10.
    发明申请
    Adenosine Receptor Antagonists 审中-公开
    腺苷受体拮抗剂

    公开(公告)号：US20100062994A1

    公开(公告)日：2010-03-11

    申请号：US12373640

    申请日：2007-07-06

    申请人： Jacob Ravn ,  Christoph Rosenbohm ,  Katrine Qvortrup ,  Troels Koch

    发明人： Jacob Ravn ,  Christoph Rosenbohm ,  Katrine Qvortrup ,  Troels Koch

    IPC分类号： A61K31/52 ,  C07H19/167 ,  A61P43/00

    CPC分类号： C07D473/00 ,  C07H19/16

    摘要： The present application discloses locked nucleoside compounds of the Formula I which act as antagonists of adenosine receptors, in particular the adenosine A3 receptor, and the use of such adenosine A3 receptor compounds in medicine, e.g. for the treatment or alleviation or prophylaxis of selected from the group consisting of pain; inflammatory diseases, arthritis, multiple sclerosis, inflammation, asthma and psoriasis; gastro-intestinal disorders; allergy; disorders associated with mast cell or eosinophil activation and degranulation; cardio-vascular disorders; cutaneous diseases; wound healing; opthalmological disorders; respiratory disorders; kidney diseases; central nervous system disorders; Alzheimer's disease, Creutzfeldt-Jacob disease, Huntington's disease and Parkinson's disease; trauma and seizure; diabetes; osteoporosis; diseases of the immune system; cancers, infections; high blood pressure, locomotor hyperactivity, hypertension and depression; acute hypoxia; neonatal hypoxia, hypoxia and chronic hypoxia; and infertility.

    摘要翻译： 本申请公开了作为腺苷受体，特别是腺苷A3受体的拮抗剂的式I的锁定核苷化合物，以及这些腺苷A3受体化合物在医学中的应用。 用于治疗或减轻或预防选自疼痛的组; 炎性疾病，关节炎，多发性硬化，炎症，哮喘和银屑病; 胃肠道疾病; 过敏; 与肥大细胞或嗜酸性粒细胞活化和脱颗粒相关的疾病; 心血管疾病; 皮肤病; 伤口愈合; 眼科疾病; 呼吸系统疾病; 肾脏疾病; 中枢神经系统疾病; 阿尔茨海默病，克雅氏病，亨廷顿氏病和帕金森病; 创伤和癫痫发作; 糖尿病; 骨质疏松症 免疫系统疾病; 癌症，感染; 高血压，运动过度活动，高血压和抑郁; 急性缺氧 新生儿缺氧，缺氧和慢性缺氧; 和不育症。