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1. 发明申请

US20050203042A1 Oligomeric compounds for the modulation of Bcl-2 失效
标题翻译：用于调节Bcl-2的低聚物
公开(公告)号：US20050203042A1
公开(公告)日：2005-09-15
申请号：US11021729
申请日：2004-12-23
申请人： Miriam Frieden , Jens Hansen , Henrik Orum , Majken Westergaard , Charlotte Thrue
发明人： Miriam Frieden , Jens Hansen , Henrik Orum , Majken Westergaard , Charlotte Thrue
IPC分类号： A61K48/00 , C07H21/02 , C12N15/113
CPC分类号： C12N15/1135 , A61K48/00 , C07H21/00 , C12N2310/315 , C12N2310/3231
摘要： The present invention provides improved oligomeric compound, in particular oligonucleotide compounds, and methods for modulating the expression of the Bcl-2 gene in humans. In particular, this invention relates to oligomeric compounds of 10-30 nucleobases in length which comprise a target binding domain that is specifically hybridizable to a region ranging from base position No. 1459 (5′) to No. 1476 (3′) of the human Bcl-2 mRNA, said target binding domain having the formula: 5′-[(DNA/RNA)0-1-(LNA/LNA*)2-7-(DNA/RNA/LNA*)4-14-(LNA/LNA*)2-7-(DNA/RNA)0-1]-3 and said target binding domain comprising at least two LNA nucleotides or LNA analogue nucleotides linked by a phosphorothioate group (—O—P(O,S)—O—). In particular the oligo is predominantly or fully thiolated. The invention also provides the use of such oligomers or conjugates or chimera for the treatment of various diseases associated with the expression of the Bcl-2 gene, such as cancer.
摘要翻译：本发明提供了改进的低聚化合物，特别是寡核苷酸化合物，以及调节人类Bcl-2基因表达的方法。特别地，本发明涉及长度为10-30个核碱基的寡聚化合物，其包含与从第1459（5'）至第1476（3'）的基础位置区别特异性杂交的靶结合结构域所述目标结合结构域具有下式：5' - [（DNA / RNA）0-1 - （LNA / LNA *）2-7 - （DNA / RNA / LNA *）4-14 - （LNA / LNA *）2-7 - （DNA / RNA）

2. 发明申请

US20060128646A1 Antisense design 有权
标题翻译：反义设计
公开(公告)号：US20060128646A1
公开(公告)日：2006-06-15
申请号：US10535472
申请日：2003-11-18
申请人： Signe Christensen , Nikolaj Mikkelsen , Miriam Frieden , Henrik Hansen , Troels Koch , Daniel Pedersen , Christoph Rosenbohm , Charlotte Thrue , Majken Westergaard
发明人： Signe Christensen , Nikolaj Mikkelsen , Miriam Frieden , Henrik Hansen , Troels Koch , Daniel Pedersen , Christoph Rosenbohm , Charlotte Thrue , Majken Westergaard
IPC分类号： A61K48/00 , C07K14/47 , C07H21/02
CPC分类号： C12N15/113 , A61K31/7088 , C07H19/04 , C07H19/06 , C07H19/16 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/111 , C12N15/1137 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/341 , C12N2310/344 , C12N2320/30 , C12N2320/51
摘要： A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.
摘要翻译：一种新型的药物，其包含可用于反义治疗的锁定核酸（LNA）。这些新型寡核苷酸具有改善的反义性质。所述新型寡核苷酸由至少一种选自β-D-thio / amino-LNA或α-L-氧基/硫代/氨基-LNA的LNA组成。包含LNA的寡核苷酸还可以包括DNA和/或RNA核苷酸。

3. 发明申请

US20060252721A1 Potent LNA oligonucleotides for the inhibition of HIF-1a expression 有权
标题翻译：用于抑制HIF-1a表达的强大的LNA寡核苷酸
公开(公告)号：US20060252721A1
公开(公告)日：2006-11-09
申请号：US11271686
申请日：2005-11-09
申请人： Majken Westergaard , Charlotte Thrue , Frank Rasmussen , Henrik Hansen
发明人： Majken Westergaard , Charlotte Thrue , Frank Rasmussen , Henrik Hansen
IPC分类号： A61K48/00 , C07H21/02
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/345 , C12N2310/346
摘要： The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5′-(Tx)GxGxcsasasgscsastscscsTxGxT-3′ and 5′-(Gx)TxTxascstsgscscststscsTxTxA-3′, wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analogue or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighbouring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighbouring nucleotides/LNA nucleotide analogues, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g. diabetic retinopathy, macular degeneration (ARMD), psoriasis, rheumatoid arthritis and other inflammatory diseases.
摘要翻译：本公开内容涉及由选自下组的序列组成的LNA寡核苷酸：5' - （T x）X G x 例如，本发明的一个或多个实施方案，其中， x> T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T -3'和5' - （G x x）T x x T x 其中一个或多个第一个或更多个> 其中大写字母表示β-D-氧基，其中大写字母表示β-D-氧基， -LNA核苷酸类似物，小写字母表示2-脱氧核苷酸，下划线表示β-D-氧-LNA核苷酸类似物或2-脱氧核苷酸，下标“s”表示相邻核苷酸/ LNA核苷酸类似物之间的硫代磷酸酯连接，下标 “x”表示相邻核苷酸/ LNA核苷酸类似物之间的硫代磷酸酯连接或磷酸二酯连接，并且其中该序列是选择性的最多延伸5个2-脱氧核苷酸单位。 LNA寡核苷酸可用于调节缺氧诱导因子-1a（HIF-1a）的表达，例如，在治疗癌症疾病，抑制血管发生，诱导细胞凋亡，预防细胞增殖或治疗血管生成疾病，例如，糖尿病性视网膜病变，黄斑变性（ARMD），牛皮癣，类风湿性关节炎等炎症性疾病。

4. 发明申请

US20050014712A1 Oligomeric compounds for the modulation survivin expression 有权
标题翻译：用于调节存活蛋白表达的寡聚化合物
公开(公告)号：US20050014712A1
公开(公告)日：2005-01-20
申请号：US10776934
申请日：2004-02-10
申请人： Bo Hansen , Charlotte Thrue , Majken Westergaard , Kamille Petersen , Margit Wissenbach
发明人： Bo Hansen , Charlotte Thrue , Majken Westergaard , Kamille Petersen , Margit Wissenbach
IPC分类号： C07H21/04 , A61K48/00
CPC分类号： C07H21/04
摘要： Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin 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：提供针对存活蛋白基因的寡核苷酸用于调节存活蛋白的表达。组合物包含针对编码存活蛋白的核酸的寡核苷酸，特别是反义寡核苷酸。提供了使用这些化合物调节存活蛋白表达和治疗与存活素过表达，突变存活蛋白或两者表达相关的疾病的方法。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。

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