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1.发明申请公开(公告)号：US20140294897A1
公开(公告)日：2014-10-02
申请号：US13851294
申请日：2013-03-27
IPC分类号： C07H21/04 , A61K31/7088 , A61N5/10 , A61K45/06
CPC分类号： C12N15/113 , A61K31/7088 , A61K45/06 , A61N5/10 , C07H21/04 , C12N15/111 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/341 , C12N2320/30
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。
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公开(公告)号：US5077344A
公开(公告)日：1991-12-31
申请号：US75599
申请日：1987-07-20
申请人： Ole Buchardt , Henrik F. Hansen , Roald B. Jensen
发明人： Ole Buchardt , Henrik F. Hansen , Roald B. Jensen
摘要： Method for modifying polymers with pendant carboxyl groups through reaction with nucleophilic reagent, e.g., sulfide, selenide, cyanide, to produce a carrier on which biologically active materials such as enzymes may be immobilized.
摘要翻译： 通过与亲核试剂例如硫化物，硒化物，氰化物反应来改性具有侧基羧基的聚合物的方法，以产生其上可固定有生物活性物质如酶的载体。
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3.发明申请公开(公告)号：US20110183931A1
公开(公告)日：2011-07-28
申请号：US13079525
申请日：2011-04-04
IPC分类号： A61K31/7052 , A61K31/704 , A61P35/00
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)TxascstsgscscststscsTxTxA-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）TxascstsgscscststscscTxTxA-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。
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4.发明申请公开(公告)号：US20090286859A1
公开(公告)日：2009-11-19
申请号：US12477261
申请日：2009-06-03
IPC分类号： A61K31/7088 , A61P35/00
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： 本发明涉及由选自5' - （Tx）GxGxcsasasgscsastscscsTxGxT-3'和5-（Gx）TxTxascstsgscscststscscTTTTXA-3'的序列组成的LNA寡核苷酸，其中大写字母表示β-D-氧 - 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。
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5.发明授权公开(公告)号：US07589190B2
公开(公告)日：2009-09-15
申请号：US11271686
申请日：2005-11-09
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： 本发明涉及由选自5' - （Tx）GxGxcsasasgscsastscscs TxGxT-3'和5' - （ Gx）TxTxascstsgscscststscsTxTxA-3'，其中大写字母表示β-D-氧-LNA核苷酸类似物，小字母表示2-脱氧核苷酸，下划线指定 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”表示硫代磷酸酯连接或相邻核苷酸/ LNA核苷酸类似物，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。
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公开(公告)号：US5315016A
公开(公告)日：1994-05-24
申请号：US960102
申请日：1992-10-13
申请人： Henrik F. Hansen , Kim Kjoernaes
发明人： Henrik F. Hansen , Kim Kjoernaes
IPC分类号： C07D493/04 , C07D307/77
CPC分类号： C07D493/04
摘要： A process for preparing crystalline, anhydrous podophyllotoxin from a podophyllotoxin product comprises dissolving the product in a non-aromatic and non-halogenated solvent which has a boiling point at atmospheric pressure not exceeding 130.degree. C., and which contains at the most about 1% v/v of water, cooling the solution to precipitate crystals of podophyllotoxin, isolating the crystals and drying them at a temperature which during the drying procedure is increased but is always such that it is below the temperature at which the crystals sinter or melt, the drying being continued until the melting point is in a range of 183.degree.-184.degree. C. and the residual amount of solvent is at the most 500 ppm. When the starting material contains complexed or adsorbed organic solvent, an initial azeotropic evaporation treatment is performed to remove this solvent. The yield of pure podophyllotoxin is greatly increased by adding water to the crystallization mixture.
摘要翻译： 从鬼臼毒产物制备结晶的无水鬼臼毒素的方法包括将产物溶解在沸点在大气压不超过130℃的非芳族和非卤化溶剂中，并且其含有最多约1％ v / v的水，冷却溶液以沉淀鬼臼毒素的晶体，分离晶体并在干燥过程中增加的温度下干燥，但始终使其低于晶体烧结或熔化的温度， 继续干燥直到熔点在183〜-184℃的范围内，并且溶剂的残留量为最多500ppm。 当原料含有复合或吸附的有机溶剂时，进行初始共沸蒸发处理以除去该溶剂。 通过向结晶混合物中加入水，大大提高了纯鬼臼毒素的产率。
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