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1. 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。

2. 发明申请

US20090209748A1 OLIGONUCLEOTIDES WITH ALTERNATING SEGMENTS OF LOCKED AND NON-LOCKED NUCLEOTIDES 有权
标题翻译：具有锁定和非锁定核心的替代部分的寡核苷酸
公开(公告)号：US20090209748A1
公开(公告)日：2009-08-20
申请号：US10717434
申请日：2003-11-18
申请人： Charlotte Albaek Thrue , Christoph Rosenbohm , Henrik Frydenlund Hansen , Majken Westergaard , Nikolaj Dam Mikkelsen , Signe Christensen , Troels Koch , Daniel Sejer Pedersen , Miriam Frieden
发明人： Charlotte Albaek Thrue , Christoph Rosenbohm , Henrik Frydenlund Hansen , Majken Westergaard , Nikolaj Dam Mikkelsen , Signe Christensen , Troels Koch , Daniel Sejer Pedersen , Miriam Frieden
IPC分类号： C07H21/00
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： The present invention is directed to novel oligonucleotides with improved antisense properties. The novel oligonucleotides comprise at least one Locked Nucleic Acid (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. The present invention also provides a new class of pharmaceuticals which comprise antisense oligonucleotides and are useful in antisense therapy.
摘要翻译：本发明涉及具有改进的反义性质的新型寡核苷酸。所述新型寡核苷酸包含至少一种选自β-D-thio / amino-LNA或α-L-氧基/硫代/氨基-LNA的锁定核酸（LNA）。包含LNA的寡核苷酸还可以包括DNA和/或RNA核苷酸。本发明还提供了一类新的药物，其包含反义寡核苷酸并且可用于反义治疗。

3. 发明授权

US07687617B2 Oligonucleotides with alternating segments of locked and non-locked nucleotides 有权
标题翻译：具有锁定和非锁定核苷酸交替区段的寡核苷酸
公开(公告)号：US07687617B2
公开(公告)日：2010-03-30
申请号：US10717434
申请日：2003-11-18
申请人： Charlotte Albaek Thrue , Christoph Rosenbohm , Henrik Frydenlund Hansen , Majken Westergaard , Nikolaj Dam Mikkelsen , Signe M. Christensen , Troels Koch , Daniel Sejer Pedersen , Miriam Frieden
发明人： Charlotte Albaek Thrue , Christoph Rosenbohm , Henrik Frydenlund Hansen , Majken Westergaard , Nikolaj Dam Mikkelsen , Signe M. Christensen , Troels Koch , Daniel Sejer Pedersen , Miriam Frieden
IPC分类号： C07H21/04 , A61K31/70
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： The present invention is directed to novel oligonucleotides with improved antisense properties. The novel oligonucleotides comprise at least one Locked Nucleic Acid (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. The present invention also provides a new class of pharmaceuticals which comprise antisense oligonucleotides and are useful in antisense therapy.
摘要翻译：本发明涉及具有改进的反义性质的新型寡核苷酸。所述新型寡核苷酸包含至少一种选自β-D-thio / amino-LNA或α-L-氧基/硫代/氨基-LNA的锁定核酸（LNA）。包含LNA的寡核苷酸还可以包括DNA和/或RNA核苷酸。本发明还提供了一类新的药物，其包含反义寡核苷酸并且可用于反义治疗。

4. 发明授权

US09045518B2 Amino-LNA, thio-LNA and alpha-L-oxy-LN 有权
标题翻译：氨基-LNA，硫代-LNA和α-L-氧 - LN
公开(公告)号：US09045518B2
公开(公告)日：2015-06-02
申请号：US10535472
申请日：2003-11-18
申请人： Signe M. Christensen , Nikolaj Dam Mikkelsen , Miriam Frieden , Henrik Frydenlund Hansen , Troels Koch , Daniel Sejer Pedersen , Christoph Rosenbohm , Charlotte Albaek Thrue , Majken Westergaard
发明人： Signe M. Christensen , Nikolaj Dam Mikkelsen , Miriam Frieden , Henrik Frydenlund Hansen , Troels Koch , Daniel Sejer Pedersen , Christoph Rosenbohm , Charlotte Albaek Thrue , Majken Westergaard
IPC分类号： C07H21/04 , C07H19/16 , A61K31/7088 , C07H21/00 , C12N15/11 , C07H19/04 , C12N15/113 , C07H19/06 , 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。

5. 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）

6. 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。

7. 发明授权

US07622453B2 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：US07622453B2
公开(公告)日：2009-11-24
申请号：US11021729
申请日：2004-12-23
申请人： Miriam Frieden , Jens B. Hansen , Henrik Orum , Majken Westergaard , Charlotte A. Thrue
发明人： Miriam Frieden , Jens B. Hansen , Henrik Orum , Majken Westergaard , Charlotte A. Thrue
IPC分类号： A01N61/00 , A01N43/04 , C12Q1/68 , C07H21/02 , C07H21/04
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靶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）0-1] -3'，并且所述靶结合结构域包含由硫代磷酸酯基团连接的至少两个LNA核苷酸或LNA类似物核苷酸（-OP（O，S） - O-）。特别地，寡核苷酸主要或完全硫醇化。本发明还提供了这种寡聚物或缀合物或嵌合体用于治疗与Bcl-2基因（例如癌症）的表达相关的各种疾病的用途。

8. 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。

9. 发明申请

US20120322848A1 LNA OLIGONUCLEOTIDES AND THE TREATMENT OF CANCER 审中-公开
标题翻译： 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。

10. 发明申请

US20060154888A1 LNA oligonucleotides and the treatment of cancer 审中-公开
公开(公告)号：US20060154888A1
公开(公告)日：2006-07-13
申请号：US11272124
申请日：2005-11-09
申请人： Christoph Rosenbohm , Lene Kjaerulff , Majken Westergaard , Margit Wissenbach , Jens Hansen , Marlene Asklund
发明人： Christoph Rosenbohm , Lene Kjaerulff , Majken Westergaard , Margit Wissenbach , Jens Hansen , Marlene Asklund
IPC分类号： A61K48/00
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.

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