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    • 3. 发明申请
    • DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES
    • 具有改进的摄取和其他性质的衍生的寡核苷酸
    • WO1993007883A1
    • 1993-04-29
    • PCT/US1992009196
    • 1992-10-23
    • ISIS PHARMACEUTICALS, INC.MANOHARAN, MuthiahCOOK, Philip, DanBENNETT, Clarence, Frank
    • ISIS PHARMACEUTICALS, INC.
    • A61K31/70
    • C07H21/00C07H23/00C07J43/003C07J51/00
    • Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2'-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining linked nucleosides are 2'-deoxy-2'-fluoro, 2'-O-methoxy, 2'-O-ethoxy, 2'-O-propoxy, 2'-O-aminoalkoxy or 2'-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3' or the 5' positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.
    • 具有至少一个具有取代基的官能化核苷的连接核苷,例如类固醇分子,报道分子,非芳族亲脂性分子,报道酶,肽,蛋白质,水溶性维生素,脂溶性维生素, RNA切割复合物,金属螯合剂,卟啉,烷基化剂,芘,混合光子核酸酶/嵌入剂或芳基叠氮化物光交联剂表现出增加的细胞摄取和其它性质。 取代基可以通过连接基团连接在官能化核苷的2'-位上。 如果至少一部分剩余连接的核苷是2'-脱氧-2'-氟,则2'-O-甲氧基,2'-O-乙氧基,2'-O-丙氧基,2'-O-氨基烷氧基或2 '-O-烯丙氧基核苷,取代基可以通过连接基团在核苷的3'或5'位置或核苷的杂环碱基上或连接核苷与核苷酸之间的核苷酸间连接 相邻核苷。
    • 4. 发明申请
    • OLIGONUCLEOTIDE MODULATION OF ARACHIDONIC ACID METABOLISM
    • 阿昔洛韦酸代谢的寡糖调节
    • WO1991016901A1
    • 1991-11-14
    • PCT/US1991002628
    • 1991-04-17
    • ISIS PHARMACEUTICALS, INC.BENNETT, Clarence, FrankECKER, David, J.CROOKE, Stanely, T.MIRABELLI, Christopher, K.
    • ISIS PHARMACEUTICALS, INC.
    • A61K31/70
    • C12N15/1137C12N9/0006C12N2310/15C12N2310/315C12Q1/68C12Q1/6839C12Q1/6883C12Q2600/158C12Y113/11012C12Y301/01004C12Y301/04003C12Y303/02006G01N33/88
    • Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the synthesis or metabolism of arachidonic acid and related compounds. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with nucleic acids encoding 5-lipoxygenase, 5-lipoxygenase activating proteins, LTA4 hydrolase, phospholipase A2, phospholipase C, and coenzyme A-independent transacylase. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, and intron/exon junction. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating arachidonic acid synthesis or metabolism with an oligonucleotide or oligonucleotide analog specifically hybridizable with RNA or DNA corresponding to one of the foregoing proteins are disclosed. Methods for treatment of diseases responding to modulation of arachidonic acid synthesis or metabolism are disclosed.
    • 提供组合物和方法用于治疗和诊断适于调节花生四烯酸和相关化合物的合成或代谢的疾病。 根据优选实施方案,提供寡核苷酸和寡核苷酸类似物,其与编码5-脂氧合酶,5-脂氧合酶活化蛋白,LTA4水解酶,磷脂酶A2,磷脂酶C和辅酶A非转基因酶的核酸特异性杂交。 所述寡核苷酸包含足以实现所述特异性杂交的同一性和数目的核苷酸单元。 在其它优选的实施方案中,寡核苷酸与转录起始位点,翻译起始位点和内含子/外显子连接区特异性杂交。 公开了通过用与上述蛋白质之一相对应的RNA或DNA特异性杂交的寡核苷酸或寡核苷酸类似物调节花生四烯酸合成或代谢来治疗适于治疗性干预的疾病的方法。 公开了治疗花生四烯酸合成或代谢调节的疾病的方法。
    • 5. 发明申请
    • OLIGONUCLEOTIDE MODULATION OF CELL ADHESION
    • 细胞粘附的寡糖调节
    • WO1992003139A1
    • 1992-03-05
    • PCT/US1991005209
    • 1991-07-23
    • ISIS PHARMACEUTICALS, INC.BENNETT, Clarence, FrankMIRABELLI, Christopher, K.
    • ISIS PHARMACEUTICALS, INC.
    • A61K31/70
    • C12N15/1138A61K38/00C07K14/705C12N2310/315C12N2310/322C12N2310/3521C12N2310/3531C12N2310/3533
    • Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3'-untranslated sequences, and intervening sequences. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating cell adhesion proteins with an oligonucleotide or oligonucleotide analog specifically hybridizable with RNA or DNA corresponding to one of the foregoing proteins are disclosed. Methods for treatment of diseases responding to modulation cell adhesion molecules are disclosed.
    • 提供组合物和方法,用于治疗和诊断适于通过调节细胞间粘附分子的合成或代谢来治疗的疾病。 根据优选实施方案,提供寡核苷酸和寡核苷酸类似物,其与编码细胞间粘附分子-1,血管细胞粘附分子-1和内皮细胞粘附分子-1的核酸特异性杂交。 所述寡核苷酸包含足以实现所述特异性杂交的同一性和数目的核苷酸单元。 在其它优选实施方案中,寡核苷酸与转录起始位点,翻译起始位点,5'-非翻译序列,3'非翻译序列和插入序列特异性杂交。 公开了通过用与上述蛋白质之一相应的RNA或DNA特异性杂交的寡核苷酸或寡核苷酸调节细胞粘附蛋白来治疗患有疾病的动物的治疗方法。 公开了治疗响应于调节细胞粘附分子的疾病的方法。