公开(公告)号：US20130123479A1

公开(公告)日：2013-05-16

申请号：US13731999

申请日：2012-12-31

申请人： Peter L. Sazani ,  Henrik Orum

发明人： Peter L. Sazani ,  Henrik Orum

IPC分类号： C07H21/04

CPC分类号： C07K14/70578 ,  A61K38/00 ,  A61K48/00 ,  C07H21/04 ,  C07K14/7151 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/346 ,  C12N2320/33 ,  Y02A50/463 ,  C12N2310/3521

摘要： The present invention relates to tumor necrosis factor (TNF) antagonists and corresponding nucleic acids derived from tumor necrosis factor receptors (TNFRs) and their use in the treatment of inflammatory diseases. These proteins are soluble secreted decoy receptors that bind to TNF and prevent TNF from signaling to cells. In particular, the proteins are mammalian TNFRs that lack exon 7 and which can bind TNF and can act as a TNF antagonist.

公开(公告)号：US20060101877A1

公开(公告)日：2006-05-18

申请号：US10524594

申请日：2003-08-15

申请人： Henrik Orum ,  Ann-Marie Orum

发明人： Henrik Orum ,  Ann-Marie Orum

IPC分类号： F16B41/00

CPC分类号： E05G1/005 ,  E04H12/2223 ,  E04H12/2269 ,  F16B23/00 ,  F16B35/04 ,  F16B39/02 ,  F16B41/005 ,  Y10T70/5863

摘要： A safety-box is provided that can be attached to a hard-to-move object and used for safe and convenient storage of personal valuables in public places such as on beaches, on camping grounds, at festivals, etc. Also provided is a device, termed a safety-anchor, which can function as a hard-to-move object for securing a safety-box. Finally, the invention provides safety-fasteners that can be used to efficiently and conveniently secure a diversity of indoor and outdoor objects and items against theft and unauthorised removal.

摘要翻译： 提供了一个安全箱，可以安装在难以移动的物体上，用于在公共场所（如海滩，露营地，节日等）上安全方便地存放个人贵重物品。还提供了一种装置 ，称为安全锚，其可以用作固定安全箱的难以移动的物体。 最后，本发明提供了可用于有效和方便地确保室内和室外物体和物品的多样性以防止盗窃和未经授权的移除的安全紧固件。

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）

公开(公告)号：US20140057968A1

公开(公告)日：2014-02-27

申请号：US13794497

申请日：2013-03-11

申请人： Peter L. Sazani ,  Ryszard Kole ,  Henrik Orum

发明人： Peter L. Sazani ,  Ryszard Kole ,  Henrik Orum

IPC分类号： C12N15/113

CPC分类号： C12N15/1138 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3521

摘要： Methods and compositions are disclosed for controlling expression of TNF receptors (TNFR1 and TNFR2) and of other receptors in the TNFR superfamily using compounds that modulate splicing of pre-mRNA encoding these receptors. More specifically these compounds cause the removal of the transmembrane domains of these receptors and produce soluble forms of the receptor which act as an antagonist to reduce TNF-α activity or activity of the relevant ligand. Reducing TNF-α activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-α activity. Similarly, diseases associated with other ligands can be treated in like manner. In particular, the compounds of the invention are splice-splice switching oligomers (SSOs) which are small molecules that are stable in vivo, hybridize to the RNA in a sequence specific manner and, in conjunction with their target, are not degraded by RNAse H.

摘要翻译： 公开了使用调节编码这些受体的前mRNA的剪接的化合物来控制TNFR超家族中TNF受体（TNFR1和TNFR2）和其他受体的表达的方法和组合物。 更具体地，这些化合物引起这些受体的跨膜结构域的去除并产生作为减轻TNF-α活性或相关配体的活性的拮抗剂的可溶形式的受体。 降低TNF-α活性提供了治疗或改善与TNF-α活性相关的炎性疾病或病症的方法。 类似地，可以以相似的方式治疗与其它配体相关的疾病。 特别地，本发明的化合物是作为体内稳定的小分子的剪接切割寡聚体（SSO），以序列特异性方式与RNA杂交，并且与其目标结合不被RNA酶H降解 。

公开(公告)号：US20120322851A1

公开(公告)日：2012-12-20

申请号：US13503189

申请日：2010-10-20

申请人： Gregroy Hardee ,  Ellen Marie Straarup ,  Marie Wickstrom Lindholm ,  Henrik Orum ,  Henrik Hansen

发明人： Gregroy Hardee ,  Ellen Marie Straarup ,  Marie Wickstrom Lindholm ,  Henrik Orum ,  Henrik Hansen

IPC分类号： A61K31/712 ,  A61P3/00 ,  A61P1/16

CPC分类号： A61K31/712 ,  A61K9/0053 ,  C12N15/113 ,  C12N15/1136 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2320/30

摘要： The invention provides for LNA oligomers, for the treatment of a metabolic or liver disorder, wherein the LNA oligomer is administered orally in a unit dose of less than 50 mgs/kg, wherein the LNA oligomer is administered in the presence of a penetration (permeation) enhancer.

摘要翻译： 本发明提供用于治疗代谢或肝病症的LNA寡聚体，其中所述LNA低聚物以小于50mg / kg的单位剂量口服给药，其中所述LNA低聚物在渗透（渗透 ）增强剂。

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。

公开(公告)号：US20070105807A1

公开(公告)日：2007-05-10

申请号：US11595485

申请日：2006-11-10

申请人： Peter Sazani ,  Ryszard Kole ,  Henrik Orum

发明人： Peter Sazani ,  Ryszard Kole ,  Henrik Orum

IPC分类号： A61K48/00 ,  C07H21/02

CPC分类号： C12N15/1138 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3521

摘要： Methods and compositions are disclosed for controlling expression of TNF receptors (TNFR1 and TNFR2) and of other receptors in the TNFR superfamily using compounds that modulate splicing of pre-mRNA encoding these receptors. More specifically these compounds cause the removal of the transmembrane domains of these receptors and produce soluble forms of the receptor which act as an antagonist to reduce TNF-α activity or activity of the relevant ligand. Reducing TNF-α activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-α activity. Similarly, diseases associated with other ligands can be treated in like manner. In particular, the compounds of the invention are splice-splice switching oligomers (SSOs) which are small molecules that are stable in vivo, hybridize to the RNA in a sequence specific manner and, in conjunction with their target, are not degraded by RNAse H.

摘要翻译： 公开了使用调节编码这些受体的前mRNA的剪接的化合物来控制TNFR超家族中TNF受体（TNFR1和TNFR2）和其他受体的表达的方法和组合物。 更具体地，这些化合物引起这些受体的跨膜结构域的去除并产生作为减轻TNF-α活性或相关配体的活性的拮抗剂的可溶形式的受体。 降低TNF-α活性提供了治疗或改善与TNF-α活性相关的炎性疾病或病症的方法。 类似地，可以以相似的方式治疗与其它配体相关的疾病。 特别地，本发明的化合物是作为体内稳定的小分子的剪接切割寡聚体（SSO），以序列特异性方式与RNA杂交，并且与其目标结合不被RNA酶H降解 。

公开(公告)号：US5861250A

公开(公告)日：1999-01-19

申请号：US659529

申请日：1996-06-06

申请人： Christopher John Stanley ,  Henrik Orum ,  Mikkell Jorgensen ,  Ole Basboll

发明人： Christopher John Stanley ,  Henrik Orum ,  Mikkell Jorgensen ,  Ole Basboll

IPC分类号： G01N33/53 ,  C07H21/00 ,  C07H21/04 ,  C07K14/00 ,  C12N15/09 ,  C12Q1/68 ,  G01N33/566 ,  C12P19/34 ,  C12N15/00

CPC分类号： C07K14/003 ,  C07H21/00 ,  C12Q1/6816

摘要： A selected region of a nucleic acid is protected from attach by nuclease by completing to the nucleic acid a nucleic acid analogue of the PNA type. The surviving sequence may be detected in an assay, optionally after amplification. A PCR reaction may be sterilized and its product assayed by protecting a characterizing region of the product by PNA hybridization followed by nuclease degradation of unprotected nucleic acid.

摘要翻译： 核酸的选定区域被核酸酶保护而不被核酸与PNA型的核酸类似物完全结合。 可以在测定中，任选地在扩增后检测存活的序列。 可以对PCR反应进行灭菌，并通过PNA杂交保护产物的特征区域，然后通过未保护核酸的核酸酶降解来测定其产物。

公开(公告)号：US20110237521A1

公开(公告)日：2011-09-29

申请号：US12954250

申请日：2010-11-24

申请人： Peter L. Sazani ,  Ryszard Kole ,  Henrik Orum

发明人： Peter L. Sazani ,  Ryszard Kole ,  Henrik Orum

IPC分类号： A61K38/14 ,  C12N5/071 ,  A61K31/7088 ,  A61K31/712 ,  C07H21/04 ,  C07H21/02 ,  C07K2/00 ,  A61P17/06 ,  A61P19/02 ,  A61P29/00 ,  A61P1/16

CPC分类号： C12N15/1138 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3521

摘要： Methods and compositions are disclosed for controlling expression of TNF receptors (TNFR1 and TNFR2) and of other receptors in the TNFR superfamily using compounds that modulate splicing of pre-mRNA encoding these receptors. More specifically these compounds cause the removal of the transmembrane domains of these receptors and produce soluble forms of the receptor which act as an antagonist to reduce TNF-α activity or activity of the relevant ligand. Reducing TNF-α activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-α activity. Similarly, diseases associated with other ligands can be treated in like manner. In particular, the compounds of the invention are splice-splice switching oligomers (SSOs) which are small molecules that are stable in vivo, hybridize to the RNA in a sequence specific manner and, in conjunction with their target, are not degraded by RNAse H.

摘要翻译： 公开了使用调节编码这些受体的前mRNA的剪接的化合物来控制TNFR超家族中TNF受体（TNFR1和TNFR2）和其他受体的表达的方法和组合物。 更具体地，这些化合物引起这些受体的跨膜结构域的去除，并产生可溶性形式的受体，其作为降低TNF-α活性或相关配体活性的拮抗剂。 降低TNF-α活性提供了治疗或改善与TNF-α活性相关的炎性疾病或病症的方法。 类似地，可以以相似的方式治疗与其它配体相关的疾病。 特别地，本发明的化合物是作为体内稳定的小分子的剪接切割寡聚体（SSO），以序列特异性方式与RNA杂交，并且与其目标结合不被RNA酶H降解 。

公开(公告)号：US20090325301A1

公开(公告)日：2009-12-31

申请号：US12429165

申请日：2009-04-23

申请人： Henrik Orum ,  Ane-Ullerup Lester

发明人： Henrik Orum ,  Ane-Ullerup Lester

IPC分类号： G01N33/44 ,  G01N33/00

CPC分类号： C12Q1/6832 ,  C12Q1/6827 ,  Y10T436/143333

摘要： A method for specifically determining the presence of a target by contacting the target in the presence of other targets with a probe capable of binding to the target to form a complex of the target with the probe, where the contacting is performed in the presence of a compound enhancing the specificity of the binding or the complex formed is contacted with a compound enhancing the specificity of the binding. This method opens the way to a better discrimination between related nucleic acid sequences in diagnostic assays.

摘要翻译： 一种用于通过在其它靶标存在下使靶标与能够结合靶标的探针接触来形成目标物与探针的复合物来特异性地确定靶的存在的方法，其中在存在下进行接触 增加结合的特异性的化合物或形成的复合物与增强结合特异性的化合物接触。 该方法开辟了在诊断测定中更好地区分相关核酸序列的方法。