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1. 发明申请

WO2006050734A2 POTENT LNA OLIGONUCLEOTIDES FOR THE INHIBITION OF HIF-1A EXPRESSION 审中-公开
标题翻译：用于抑制HIF-1A表达的POTENT LNA寡核苷酸
公开(公告)号：WO2006050734A2
公开(公告)日：2006-05-18
申请号：PCT/DK2005/000721
申请日：2005-11-09
申请人： SANTARIS PHARMA A/S , RASMUSSEN, Frank Winther , WESTERGAARD, Majken , HANSEN, Henrik Frydenlund , THRUE, Charlotte Albæk
发明人： RASMUSSEN, Frank Winther , WESTERGAARD, Majken , HANSEN, Henrik Frydenlund , THRUE, Charlotte Albæk
IPC分类号： C07H21/04 , A61K31/7115 , A61K31/712 , A61K31/7125 , A61P11/06 , A61P17/06 , A61P19/02 , 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'-( T x G x G x c s a s a s a s g s c s a s t s c s c s T X G X T -3' and 5'-( G X )T X T X a s c s t s g s c s c s t s t s c s T X T X A -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-la (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 <

2. 发明申请

WO2004046160A3 AMINO-LNA, THIO-LNA AND ALPHA-L-OXY-LN 审中-公开
公开(公告)号：WO2004046160A3
公开(公告)日：2004-06-03
申请号：PCT/DK2003/000788
申请日：2003-11-18
申请人： SANTARIS PHARMA A/S , CHRISTENSEN, Signe, M. , MIKKELSEN, Nikolaj, Dam , FRIEDEN, Miriam , HANSEN, Henrik, Frydenlund , KOCH, Troels , PEDERSEN, Daniel, Sejer , ROSENBOHM, Chritoph , THRUE, Charlotte, Albæk , WESTERGAARD, Majken
发明人： CHRISTENSEN, Signe, M. , MIKKELSEN, Nikolaj, Dam , FRIEDEN, Miriam , HANSEN, Henrik, Frydenlund , KOCH, Troels , PEDERSEN, Daniel, Sejer , ROSENBOHM, Chritoph , THRUE, Charlotte, Albæk , WESTERGAARD, Majken
IPC分类号： A61K31/7088
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.

3. 发明申请

WO2004069990A2 OLIGOMERIC COMPOUNDS FOR THE MODULATION OF THIOREDOXIN EXPRESSION 审中-公开
标题翻译：用于调节四氢叶酸表达的低分子化合物
公开(公告)号：WO2004069990A2
公开(公告)日：2004-08-19
申请号：PCT/DK2004/000095
申请日：2004-02-10
申请人： SANTARIS PHARMA A/S , HANSEN, Bo , THRUE, Charlotte, Albæk , PETERSEN, Kamille, Dumong , WESTERGAARD, Majken , WISSENBACH, Margit
发明人： HANSEN, Bo , THRUE, Charlotte, Albæk , PETERSEN, Kamille, Dumong , WESTERGAARD, Majken , WISSENBACH, Margit
IPC分类号： C12N
CPC分类号： C12N15/1135 , C12N2310/31 , C12N2310/3231 , C12N2310/33 , C12N2310/3341 , C12N2310/341 , C12N2310/346
摘要： Oligonucleotides directed against the TRX gene are provided for modulating the expression of TRX. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the TRX. Methods of using these compounds for modulation of TRX expression and for the treatment of diseases associated with either overexpression of TRX, expression of mutated TRX or both are provided. Examples of diseases are cancer such as lung, 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TRX基因的寡核苷酸用于调节TRX的表达。组合物包含靶向编码TRX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TRX表达和治疗与TRX的过表达相关疾病，突变的TRX的表达或两者的方法。疾病的例子是肺癌，结肠癌，前列腺癌，胰腺癌，肺癌，肝癌，甲状腺癌，肾癌，脑癌，睾丸癌，胃肠，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。

4. 发明申请

WO2004069992A2 OLIGOMERIC COMPOUNDS FOR THE MODULATION OF RAS EXPRESSION 审中-公开
标题翻译：用于调制RAS表达的低分子化合物
公开(公告)号：WO2004069992A2
公开(公告)日：2004-08-19
申请号：PCT/DK2004/000097
申请日：2004-02-10
申请人： SANTARIS PHARMA A/S , HANSEN, Bo , THRUE, Charlotte, Albæk , PETERSEN, Kamille, Dumong , WESTERGAARD, Majken , WISSENBACH, Margit
发明人： HANSEN, Bo , THRUE, Charlotte, Albæk , PETERSEN, Kamille, Dumong , WESTERGAARD, Majken , WISSENBACH, Margit
IPC分类号： C12N
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过度表达相关的疾病，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。

5. 发明申请

WO2004069991A2 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：WO2004069991A2
公开(公告)日：2004-08-19
申请号：PCT/DK2004/000096
申请日：2004-02-10
申请人： SANTARIS PHARMA A/S , HANSEN, Bo , THRUE, Charlotte, Albæk , PETERSEN, Kamille, Dumong , WESTERGAARD, Majken , WISSENBACH, Margit
发明人： HANSEN, Bo , THRUE, Charlotte, Albæk , PETERSEN, Kamille, Dumong , WESTERGAARD, Majken , WISSENBACH, Margit
IPC分类号： C12N
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/346
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。

6. 发明申请

WO2007031081A2 RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-Bl00 EXPRESSION 审中-公开
标题翻译：用于抑制APO-Bl00表达的RNA拮抗剂化合物
公开(公告)号：WO2007031081A2
公开(公告)日：2007-03-22
申请号：PCT/DK2006/000481
申请日：2006-09-01
申请人： SANTARIS PHARMA A/S , HANSEN, Henrik, Frydenlund , HANSEN, Bo , WESTERGAARD, Majken , ROSENBOHM, Christoph , STRAARUP, Ellen, Marie
发明人： HANSEN, Henrik, Frydenlund , HANSEN, Bo , WESTERGAARD, Majken , ROSENBOHM, Christoph , STRAARUP, Ellen, Marie
IPC分类号： C12N15/11 , C07K14/77
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3515
摘要： Oligonucleotides directed against the Apo-B100 gene are provided for modulating the expression of Apo-B100. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Apo-Bl00. Methods of using these compounds for modulation of Apo-Bl00 expression and for the treatment of diseases associated with either overexpression of Apo-Bl00, expression of mutated Apo-Bl00 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Apo-B100基因的寡核苷酸用于调节Apo-B100的表达。该组合物包含靶向编码Apo-Bl00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Apo-Bl00表达以及用于治疗与Apo-Bl00的过度表达，突变的Apo-Bl00或两者的表达相关的疾病的方法。例如肺癌，乳腺癌，结肠癌，前列腺癌，胰腺癌，肺癌，肝癌，甲状腺癌，肾癌，脑癌，睾丸癌，胃癌，肠癌，肠癌，脊髓癌，鼻窦癌，膀胱癌，尿道癌或卵巢癌。寡核苷酸可以由脱氧核糖核苷或核酸类似物例如锁核酸或其组合组成。

7. 发明申请

WO2006050732A3 LNA OLIGONUCLEOTIDES AND THE TREATMENT OF CANCER 审中-公开
公开(公告)号：WO2006050732A3
公开(公告)日：2006-05-18
申请号：PCT/DK2005/000719
申请日：2005-11-09
申请人： SANTARIS PHARMA A/S , KJÆRULFF, Lene Sønderbye , ASKLUND, Marlene , WESTERGAARD, Majken , ROSENBOHM, Christoph , WISSENBACH, Margit , HANSEN, Bo
发明人： KJÆRULFF, Lene Sønderbye , ASKLUND, Marlene , WESTERGAARD, Majken , ROSENBOHM, Christoph , WISSENBACH, Margit , HANSEN, Bo
IPC分类号： C12N15/11 , A61K31/7088 , A61P35/00
摘要： The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5'- ( Me Cx )(Tx,) Me C X A s As t s c s c s a s t s g s g s Me C X A X ( G x) ( c)-3', and preferably of the general formula 5' - Me C X T X ), Me C X A s a s t s c s c s a s t s g s g s Me C x A x G x c-3', wherein capital letters designate an LNA nucleotide analogue selected from β -D-oxy-LNA, β -D-thio-LNA, β-D-amino-LNA and a-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.

8. 发明申请

WO2007031091A2 RNA ANTAGONIST COMPOUNDS FOR THE MODULATION OF P21 RAS EXPRESSION 审中-公开
标题翻译： RNA拮抗剂化合物调节P21基因表达
公开(公告)号：WO2007031091A2
公开(公告)日：2007-03-22
申请号：PCT/DK2006/000512
申请日：2006-09-15
申请人： SANTARIS PHARMA A/S , FLUITER, Kees , BAAS, Frank , HANSEN, Bo , WESTERGAARD, Majken
发明人： FLUITER, Kees , BAAS, Frank , HANSEN, Bo , WESTERGAARD, Majken
IPC分类号： A61K48/00 , C07H21/04
CPC分类号： C12N15/1135 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/3341
摘要： Oligonucleotides directed against the p21 Ras genes are provided for modulating the expression of p21 Ras. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding Ha-ras, Ki-ras and N-ras. Methods of using these compounds for modulation of p21 Ras expression and for the treatment of diseases associated with either overexpression of p21 Ras, expression of mutated p21 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 deoxyribonucleotides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.
摘要翻译：提供针对p21Ras基因的寡核苷酸用于调节p21Ras的表达。该组合物包含靶向编码Ha-ras，Ki-ras和N-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p21Ras表达以及用于治疗与p21Ras的过度表达，突变的p21Ras或两者的表达相关的疾病的方法。例如肺癌，乳腺癌，结肠癌，前列腺癌，胰腺癌，肺癌，肝癌，甲状腺癌，肾癌，脑癌，睾丸癌，胃癌，肠癌，肠癌，脊髓癌，鼻窦癌，膀胱癌，尿道癌或卵巢癌。寡核苷酸可以由脱氧核糖核苷酸或核酸类似物例如锁核酸或其组合组成。

9. 发明申请

WO2005061710A1 OLIGOMERIC COMPOUNDS FOR THE MODULATION OF BCL-2 审中-公开
标题翻译：用于调节BCL-2的低分子化合物
公开(公告)号：WO2005061710A1
公开(公告)日：2005-07-07
申请号：PCT/DK2004/000917
申请日：2004-12-23
申请人： SANTARIS PHARMA A/S , FRIEDEN, Miriam , HANSEN, Jens, Bo , ØRUM, Henrik , WESTERGAARD, Majken , THRUE, Charlotte, Albæck
发明人： FRIEDEN, Miriam , HANSEN, Jens, Bo , ØRUM, Henrik , WESTERGAARD, Majken , THRUE, Charlotte, Albæck
IPC分类号： C12N15/11
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 N°1459 (5’) to N°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，其包含可与从第1459（5'）到第1476（3'）的碱基位置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。

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