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1. 发明授权

US07846911B2 Oligomeric compounds for the modulation of HIF-1alpha expression 有权
标题翻译：低分子化合物用于调节HIF-1α表达
公开(公告)号：US07846911B2
公开(公告)日：2010-12-07
申请号：US12580126
申请日：2009-10-15
申请人： Charlotte Albaek Thrue , Anja Molhart Hog , Paul E. G. Kristjansen
发明人： Charlotte Albaek Thrue , Anja Molhart Hog , Paul E. G. Kristjansen
IPC分类号： A61K48/00
CPC分类号： A61K31/7088 , A61K31/70 , A61K38/00 , A61K45/06 , C07H21/04 , C12N15/113 , C12N2310/315 , C12N2310/3231 , C12N2310/331 , C12N2310/334 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , A61K2300/00
摘要： Oligonucleotides directed against the hypoxia-inducible factor-1α (HIP-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.
摘要翻译：提供针对缺氧诱导因子-1α（HIP-1α）基因的寡核苷酸用于调节HIF-1α的表达。组合物包含靶向编码HIF-1α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HIF-1α表达和治疗与缺氧诱导因子-1α相关疾病的方法。疾病的例子是癌症和先兆子痫。寡核苷酸可以由脱氧核糖核苷，核酸类似物或锁定核酸（LNA）或其组合构成。

2. 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。

3. 发明授权

US08357670B2 Oligomeric compounds for the modulation of HIF-1A expression 有权
标题翻译：用于调节HIF-1A表达的低聚化合物
公开(公告)号：US08357670B2
公开(公告)日：2013-01-22
申请号：US13477825
申请日：2012-05-22
申请人： Charlotte Albaek Thrue , Anja Molhart Hog , Paul E. G. Kristjansen
发明人： Charlotte Albaek Thrue , Anja Molhart Hog , Paul E. G. Kristjansen
IPC分类号： A16K48/00
CPC分类号： A61K31/7088 , A61K31/70 , A61K38/00 , A61K45/06 , C07H21/04 , C12N15/113 , C12N2310/315 , C12N2310/3231 , C12N2310/331 , C12N2310/334 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , A61K2300/00
摘要： Oligonucleotides directed against the hypoxia-inducible factor-1α (HIF-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.
摘要翻译：提供针对缺氧诱导因子-1α（HIF-1α）基因的寡核苷酸用于调节HIF-1α的表达。组合物包含靶向编码HIF-1α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HIF-1α表达和治疗与缺氧诱导因子-1α相关疾病的方法。疾病的例子是癌症和先兆子痫。寡核苷酸可以由脱氧核糖核苷，核酸类似物或锁定核酸（LNA）或其组合构成。

4. 发明授权

US08207140B2 Oligomeric compounds for the modulation of HIF-1α expression 有权
标题翻译：低分子化合物用于调节HIF-1α表达
公开(公告)号：US08207140B2
公开(公告)日：2012-06-26
申请号：US12913173
申请日：2010-10-27
申请人： Charlotte Albaek Thrue , Anja Molhart Hog , Paul E. G. Kristjansen
发明人： Charlotte Albaek Thrue , Anja Molhart Hog , Paul E. G. Kristjansen
IPC分类号： A61K48/00
CPC分类号： A61K31/7088 , A61K31/70 , A61K38/00 , A61K45/06 , C07H21/04 , C12N15/113 , C12N2310/315 , C12N2310/3231 , C12N2310/331 , C12N2310/334 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , A61K2300/00
摘要： Oligonucleotides directed against the hypoxia-inducible factor-1α (HIF-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.
摘要翻译：提供针对缺氧诱导因子-1α（HIF-1α）基因的寡核苷酸用于调节HIF-1α的表达。组合物包含靶向编码HIF-1α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HIF-1α表达和治疗与缺氧诱导因子-1α相关疾病的方法。疾病的例子是癌症和先兆子痫。寡核苷酸可以由脱氧核糖核苷，核酸类似物或锁定核酸（LNA）或其组合构成。

5. 发明申请

US20110224285A1 OLIGOMERIC COMPOUNDS FOR THE MODULATION OF HIF-1A EXPRESSION 有权
标题翻译：用于调节HIF-1A表达的低分子化合物
公开(公告)号：US20110224285A1
公开(公告)日：2011-09-15
申请号：US12913173
申请日：2010-10-27
申请人： Charlotte Albaek Thrue , Anja Molhart Høg , Paul E.G. Kristjansen
发明人： Charlotte Albaek Thrue , Anja Molhart Høg , Paul E.G. Kristjansen
IPC分类号： A61K31/7088 , A61P35/00 , A61P31/12
CPC分类号： A61K31/7088 , A61K31/70 , A61K38/00 , A61K45/06 , C07H21/04 , C12N15/113 , C12N2310/315 , C12N2310/3231 , C12N2310/331 , C12N2310/334 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , A61K2300/00
摘要： Oligonucleotides directed against the hypoxia-inducible factor-1α (HIF-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.
摘要翻译：提供针对缺氧诱导因子-1α（HIF-1α）基因的寡核苷酸用于调节HIF-1α的表达。组合物包含靶向编码HIF-1α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HIF-1α表达和治疗与缺氧诱导因子-1α相关疾病的方法。疾病的例子是癌症和先兆子痫。寡核苷酸可以由脱氧核糖核苷，核酸类似物或锁定核酸（LNA）或其组合构成。

6. 发明申请

US20120088907A1 OLIGOMERIC COMPOUNDS FOR THE MODULATION OF SURVIVIN EXPRESSION 审中-公开
标题翻译：用于调节表达蛋白的低分子化合物
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。

7. 发明授权

US07939507B2 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：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。

8. 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。

9. 发明授权

US08026355B2 Oligomeric compounds for the modulation of survivin expression 失效
标题翻译：用于调节存活蛋白表达的低聚化合物
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。

10. 发明申请

US20100292311A1 OLIGOMERIC COMPOUNDS FOR THE MODULATION OF SURVIVIN EXPRESSION 失效
标题翻译：用于调节表达蛋白的低分子化合物
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。

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