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    • 6. 发明授权
    • Oligonucleotide inhibitors of bcl-xL
    • bcl-xL的寡核苷酸抑制剂
    • US07074769B2
    • 2006-07-11
    • US09753169
    • 2001-01-02
    • Cy A. SteinPaul CossumRobert RandoJoshua Ojwang
    • Cy A. SteinPaul CossumRobert RandoJoshua Ojwang
    • A01N43/04A61K31/70C07H21/00C07H21/04
    • C07H21/00C07H19/06C07H19/12C07H19/16
    • This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG. 1. This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A′, B, C, C′, D, E, E, E′, F, G, G′, H, H′, I, I′, J, K, K′, L, L′, M, or M′ of FIGS. 2A and 2B. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds. In addition, this invention provides a method of treating cancer, comprising introducing into a tumor cell an effective amount of the the above-described antisense oligonucleotide, thereby reducing the levels of bcl-xL protein produced and treating cancer. This invention also provides the above-described methods, wherein the introducing comprises using porphyrin or lipofectin as a delivery agent. This invention also provides the above-described pharmaceutical compositions, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention further provides the above-described pharmaceutical compositions, wherein the pharmaceutical composition comprises tetra meso-(4-methylpyridyl)porphine or tetra meso-(anilinium)porphine or a combination thereof.
    • 本发明提供了包含来自序列A,B,C,D,E,F,G,H,I,J,K,L的碱基的10个或更多个连续碱基或碱基类似物的反义寡核苷酸或其类似物, M。 本发明还提供了上述反义寡核苷酸,其中核苷酸序列包含核苷酸序列A,A',B,C,C',D,E,E,E',F,G,G' H',I,I',J,K,K',L,L',M或M' 2A和2B。本发明还提供了上述反义寡核苷酸,其中寡核苷酸被包封在脂质体或纳米颗粒中。 本发明还提供了上述反义寡核苷酸,其中磷酸骨架包含硫代磷酸酯键。 此外,本发明提供了一种治疗癌症的方法,包括向肿瘤细胞中引入有效量的上述反义寡核苷酸,从而降低产生的bcl-xL蛋白的水平和治疗癌症。 本发明还提供了上述方法,其中引入包括使用卟啉或脂质体作为递送剂。 本发明还提供了上述药物组合物,其中寡核苷酸被包封在脂质体或纳米颗粒中。 本发明还提供了上述药物组合物,其中所述药物组合物包含四内消旋 - (4-甲基吡啶基)卟吩或四中 - (苯胺)卟吩或其组合。