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1. 发明申请

WO2007028065A3 CHIMERIC OLIGOMERIC COMPOUNDS FOR MODULATION OF SPLICING 审中-公开
标题翻译：用于调制分离的CHIMERIC低分子化合物
公开(公告)号：WO2007028065A3
公开(公告)日：2007-09-27
申请号：PCT/US2006034308
申请日：2006-08-29
申请人： ISIS PHARMACEUTICALS INC , ERCOLE BIOTECH INC , BENNETT C FRANK , DEAN NICHOLAS M , KOLE RYSZARD , KOPCZYNSKI CASEY C
发明人： BENNETT C FRANK , DEAN NICHOLAS M , KOLE RYSZARD , KOPCZYNSKI CASEY C
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , C12N15/111 , C12N15/1135 , C12N2310/321 , C12N2310/322 , C12N2310/346 , C12N2320/33 , C12N2310/3525 , C12N2310/3533 , C12N2310/3531
摘要： Disclosed herein are compounds, compositions and methods for modulating splicing of a selected target mRNA. Further provided are uses of the disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Methods of enhancing cellular uptake, modulating tissue distribution and enhancing pharmacological activity of RNase H-independent antisense oligonucleotides are also provided.
摘要翻译：本文公开了用于调节选定靶mRNA的剪接的化合物，组合物和方法。还提供了所公开的化合物和组合物在制备用于治疗疾病和病症的药物中的用途。还提供了增强细胞摄取，调节组织分布和增强RNase H非依赖性反义寡核苷酸的药理活性的方法。

2. 发明申请

WO2007058894A3 SPLICE SWITCHING OLIGOMERS FOR TNF SUPERFAMILY RECEPTORS AND THEIR USE IN TREATMENT OF DISEASE 审中-公开
标题翻译： TNF超家族受体的SPLICE切换寡核苷酸及其在治疗疾病中的应用
公开(公告)号：WO2007058894A3
公开(公告)日：2007-08-23
申请号：PCT/US2006043651
申请日：2006-11-10
申请人： UNIV NORTH CAROLINA , ERCOLE BIOTECH INC , SANTARIS PHARMA AS , SAZANI PETER L , KOLE RYSZARD , ORUM HENRIK
发明人： SAZANI PETER L , KOLE RYSZARD , ORUM HENRIK
IPC分类号： A61K31/712 , A61K31/7125 , A61P1/16 , A61P29/00 , A61P31/00 , C07H21/00 , C12N15/11 , 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 (TNFRl 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-a activity or activity of the relevant ligand. Reducing TNF-a activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-a 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。更具体地说，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相关配体的TNF-α活性或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，可以以类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。

3. 发明申请

WO2008051306A1 SOLUBLE TNF RECEPTORS AND THEIR USE IN TREATMENT OF DISEASE 审中-公开
标题翻译：可溶性TNF受体及其在治疗疾病中的应用
公开(公告)号：WO2008051306A1
公开(公告)日：2008-05-02
申请号：PCT/US2007010556
申请日：2007-05-01
申请人： ERCOLE BIOTECH INC , UNIV NORTH CAROLINA , SAZANI PETER L , GRAZIEWICZ MARIA , KOLE RYSZARD
发明人： SAZANI PETER L , GRAZIEWICZ MARIA , KOLE RYSZARD
IPC分类号： C12N15/12 , A61K38/17 , A61K48/00 , A61P29/00 , C07H21/00 , C07K14/715 , C12N15/113
CPC分类号： C07K14/7151 , C12N15/1138 , C12N2310/11 , C12N2310/3231
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.
摘要翻译：本发明涉及肿瘤坏死因子（TNF）拮抗剂和衍生自肿瘤坏死因子受体（TNFR）的相应核酸及其在治疗炎性疾病中的用途。这些蛋白质是可溶性分泌的诱饵受体，其结合TNF并阻止TNF向信号传导。特别地，蛋白质是缺乏外显子7并且可以结合TNF并且可以作为TNF拮抗剂的哺乳动物TNFR。

4. 发明申请

WO2004028464A3 METHODS AND COMPOSITIONS FOR MODIFICATION OF SPLICING OF PRE-MRNA 审中-公开
标题翻译：用于修改PRE-MRNA分离的方法和组合物
公开(公告)号：WO2004028464A3
公开(公告)日：2004-07-08
申请号：PCT/US0330423
申请日：2003-09-26
申请人： UNIV NORTH CAROLINA , KOLE RYSZARD
发明人： KOLE RYSZARD
IPC分类号： A61K20060101 , C12N15/63 , C12P19/34 , C12Q1/68 , G01N33/68
CPC分类号： C12N15/63
摘要： The present invention provides a method of preventing a splicing event in a pre-mRNA molecule, comprising contacting the pre-mRNA and/or elements of the splicing machinery with a small molecule compound identified according to the methods described herein to prevent the splicing event in the pre-mRNA molecule. Further provided is a method of inducing a splicing event in a pre-mRNA molecule, comprising contacting the pre-mRNA and/or elements of the splicing machinery with a small molecule compound identified according to the methods described herein to induce the splicing event in the pre-mRNA molecule. Furthermore, a method is provided herein of treating a patient having a disorder associated with an alternative or aberrant splicing event in a pre-mRNA molecule, comprising administering to the patient a therapeutically effective amount of a compound identified according to the methods described herein to prevent an alternative or aberrant splicing event in a pre-mRNA molecule, thereby treating the patient.
摘要翻译：本发明提供了预防mRNA前体分子内的剪接事件的方法，包括使剪接机械的前mRNA和/或元件与根据本文所述的方法鉴定的小分子化合物接触，以防止剪接事件前mRNA分子。进一步提供的是诱导前mRNA分子中的剪接事件的方法，包括使剪接机械的前mRNA和/或元件与根据本文所述的方法鉴定的小分子化合物接触以诱导剪接事件前mRNA分子。此外，本文提供了一种治疗患有与mRNA前体分子内的替代或异常剪接事件相关的疾病的患者的方法，包括向患者施用治疗有效量的根据本文所述方法鉴定的化合物以预防前mRNA分子中的替代或异常剪接事件，从而治疗患者。

5. 发明申请

WO2008153933A3 SOLUBLE HER2 AND HER3 SPLICE VARIANT PROTEINS, SPLICE-SWITCHING OLIGONUCLEOTIDES, AND THEIR USE IN THE TREATMENT OF DISEASE 审中-公开
标题翻译：可溶性HER2和HER3淋巴细胞变异蛋白，分子切换寡核苷酸及其在治疗疾病中的应用
公开(公告)号：WO2008153933A3
公开(公告)日：2017-02-02
申请号：PCT/US2008007111
申请日：2008-06-06
申请人： AVI BIOPHARMA INC , UNIV NORTH CAROLINA CHAPEL HILL , KOLE RYSZARD , SAZANI PETER , WAN JING
发明人： KOLE RYSZARD , SAZANI PETER , WAN JING
IPC分类号： A01N37/18 , C07H21/02 , C07K1/00
CPC分类号： C07K14/71 , A61K38/00
摘要： Soluble epidermal growth factor receptors 2 and 3 (HER2 and HER3) splice variant proteins with HER2 and HER3 antagonist activity and anti-proliferative properties, as well as the corresponding nucleic acids, are provided for treatment of proliferative diseases, in particular cancer. Also provided are compositions and methods for inducing expression of these splice variants, including splice switching oligonucleotides that modulate splicing of pre-mRNA that codes for these receptors.
摘要翻译：可溶性表皮生长因子受体2和3（HER2和HER3）剪接具有HER2和HER3拮抗剂活性和抗增殖特性的变体蛋白以及相应的核酸被用于治疗增殖性疾病，特别是癌症。还提供了用于诱导这些剪接变体表达的组合物和方法，包括调节编码这些受体的前mRNA的剪接的剪接切换寡核苷酸。

6. 发明申请

WO2014011573A3 OLIGONUCLEOTIDE INHIBITORS OF DNA METHYLTRANSFERASES AND THEIR USE IN TREATING DISEASES 审中-公开
标题翻译： DNA甲基衍生物的寡核苷酸抑制剂及其在治疗疾病中的应用
公开(公告)号：WO2014011573A3
公开(公告)日：2015-04-09
申请号：PCT/US2013049624
申请日：2013-07-09
申请人： METHEOR THERAPEUTICS CORP , SLEDZIEWSKI ANDREW Z , DEVOS THEODORE , KOLE RYSZARD
发明人： SLEDZIEWSKI ANDREW Z , DEVOS THEODORE , KOLE RYSZARD
IPC分类号： A61K48/00
CPC分类号： C12N15/1137 , C12N2310/13 , C12N2310/33 , C12N2310/3341 , C12N2310/531 , C12Y201/01037
摘要： Modified oligonucleotides comprising CpG sites, wherein the cytosine is replaced by cytosine analogs are provided as well as methods of making the oligonucleotides and their use in inhibiting DNA Methyltransferase, inhibiting or reversing methylation of genes and in treating cancer, tumorigenesis and hyper-proliferative disorders.
摘要翻译：提供了包含CpG位点的修饰的寡核苷酸，其中胞嘧啶被胞嘧啶类似物替代，以及制备寡核苷酸及其在抑制DNA甲基转移酶中的用途，抑制或逆转基因甲基化和治疗癌症，肿瘤发生和高增殖性疾病的方法。

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