公开(公告)号：US20120088907A1

公开(公告)日：2012-04-12

申请号：US13183365

申请日：2011-07-14

申请人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： C07H21/04

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。

公开(公告)号：US20100292311A1

公开(公告)日：2010-11-18

申请号：US12765673

申请日：2010-04-22

申请人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K31/713 ,  A61P35/00

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。

公开(公告)号：US20080188432A1

公开(公告)日：2008-08-07

申请号：US11640123

申请日：2006-12-15

申请人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Bo Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K31/7052 ,  C07H21/04

CPC分类号： C12N15/1135 ,  A61K38/00 ,  C07H21/04 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/33 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346

摘要： Oligonucleotides directed against the Ha-ras gene are provided for modulating the expression of Ha-ras. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Ha-ras. Methods of using these compounds for modulation of Ha-ras expression and for the treatment of diseases associated with either overexpression of Ha-ras, expression of mutated Ha-ras 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Ha-ras基因的寡核苷酸用于调节Ha-ras的表达。 组合物包含针对编码Ha-ras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Ha-ras表达和治疗与Ha-ras的过表达有关的疾病，突变型Ha-ras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。

公开(公告)号：US08026355B2

公开(公告)日：2011-09-27

申请号：US12765673

申请日：2010-04-22

申请人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： C07H21/04

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。

公开(公告)号：US07741309B2

公开(公告)日：2010-06-22

申请号：US12493625

申请日：2009-06-29

申请人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Jens Bo Rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： 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。

公开(公告)号：US20090318362A1

公开(公告)日：2009-12-24

申请号：US12493625

申请日：2009-06-29

申请人： Jens Bo rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

发明人： Jens Bo rode Hansen ,  Charlotte Albaek Thrue ,  Majken Westergaard ,  Kamille Dumong Petersen ,  Margit Wissenbach

IPC分类号： A61K38/10 ,  A61P35/00

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。

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。

公开(公告)号：US07939507B2

公开(公告)日：2011-05-10

申请号：US12477261

申请日：2009-06-03

申请人： Majken Westergaard ,  Charlotte Albaek Thrue ,  Frank Winther Rasmussen ,  Henrik Frydenlund Hansen

发明人： Majken Westergaard ,  Charlotte Albaek Thrue ,  Frank Winther Rasmussen ,  Henrik Frydenlund Hansen

IPC分类号： A01N43/04 ,  C12Q1/68 ,  C12N15/63 ,  C07H21/02 ,  C07H21/04

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5' - （Tx）GxGxcsasasgscsastscscsTxGxT-3'和5' - （Gx）TxTxascstsgscscststscscTTTXA-3'的序列组成的LNA寡核苷酸，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，并且其中该序列任选地延伸多达五个2-脱氧核苷酸单元。 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。

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。

公开(公告)号：US08410071B2

公开(公告)日：2013-04-02

申请号：US13079525

申请日：2011-04-04

申请人： Majken Westergaard ,  Charlotte Albaek Thrue ,  Frank Winther Rasmussen ,  Henrik Frydenlund Hansen

发明人： Majken Westergaard ,  Charlotte Albaek Thrue ,  Frank Winther Rasmussen ,  Henrik Frydenlund Hansen

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C12N15/63 ,  A01N43/04 ,  C07H21/04

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 neighboring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighboring 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5' - （Tx）GxGxcsasasgscsastscscsTxGxT-3'和5' - （Gx）TxTxascstsgscscststscscTTTXA-3'的序列组成的LNA寡核苷酸，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 在相邻核苷酸/ LNA核苷酸类似物之间是硫代磷酸酯连接或磷酸二酯连接，并且其中所述序列任选地延伸多达五个2-脱氧核苷酸单元。 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。