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1. 发明授权

US07074769B2 Oligonucleotide inhibitors of bcl-xL 失效
标题翻译： bcl-xL的寡核苷酸抑制剂
公开(公告)号：US07074769B2
公开(公告)日：2006-07-11
申请号：US09753169
申请日：2001-01-02
申请人： Cy A. Stein , Paul Cossum , Robert Rando , Joshua Ojwang
发明人： Cy A. Stein , Paul Cossum , Robert Rando , Joshua Ojwang
IPC分类号： A01N43/04 , A61K31/70 , C07H21/00 , C07H21/04
CPC分类号： C07H21/00 , C07H19/06 , C07H19/12 , C07H19/16
摘要： 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.
摘要翻译：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。

2. 发明授权

US5545626A Method of treating glaucoma with oligonucleotides 失效
标题翻译：用寡核苷酸治疗青光眼的方法
公开(公告)号：US5545626A
公开(公告)日：1996-08-13
申请号：US184223
申请日：1994-01-19
申请人： Cy A. Stein , Martin B. Wax
发明人： Cy A. Stein , Martin B. Wax
IPC分类号： A61K20060101 , A61K31/665 , A61K31/70 , A61K47/48 , A61K31/735
CPC分类号： A61K31/70 , A61K47/48092 , Y10S514/913
摘要： The present invention provides a method of treating glaucoma which comprises administering to a subject an effective amount of an oligonucleotide which may be substituted or modified in its phosphate, sugar, or base, so as to decrease intraocular pressure and thereby treat the glaucoma.
摘要翻译：本发明提供一种治疗青光眼的方法，其包括向受试者施用有效量的可在其磷酸盐，糖或碱中被取代或修饰的寡核苷酸，以降低眼内压，从而治疗青光眼。

3. 发明授权

US06867043B2 Peptides that deliver antisense oligonucleotides which downregulate protein expression in cells 失效
公开(公告)号：US06867043B2
公开(公告)日：2005-03-15
申请号：US10002884
申请日：2001-11-02
申请人： Cy A. Stein , Luba Benimetskaya , Nancy Guzzo-Pernell
发明人： Cy A. Stein , Luba Benimetskaya , Nancy Guzzo-Pernell
IPC分类号： A61K38/17 , A61K48/00 , C12N15/87 , C12N15/63
CPC分类号： C12N15/87 , A61K38/1709 , A61K48/0041
摘要： The present invention provides a peptide that can complex with an oligonucleotide, e.g. an antisense oligonucleotide, and deliver it into a cell. The present invention also provides compositions comprising a complex of such a peptide and an oligonucleotide and methods of delivering an oligonucleotide into a cell and of inhibiting protein expression using such compositions. The present invention also provides a method of making such a complex, a method of sensitizing cells to anti-cancer agents such as paclitaxel, and pharmaceutical compositions.

4. 发明授权

US5792657A Steroid secreting human adrenocortical carcinoma cell lines 失效
标题翻译：类固醇分泌人肾上腺皮质癌细胞系
公开(公告)号：US5792657A
公开(公告)日：1998-08-11
申请号：US486679
申请日：1995-06-07
申请人： Adi F. Gazdar , Renato V. La Rocca , Cy A. Stein , Charles E. Myers , Herbert K. Oie
发明人： Adi F. Gazdar , Renato V. La Rocca , Cy A. Stein , Charles E. Myers , Herbert K. Oie
IPC分类号： C12N5/09 , C12N5/00 , C12P1/00 , C12P21/04 , C12P33/00
CPC分类号： C12N5/0693
摘要： Continuous cell lines have been established from adrenocortical corcinomas. The cell lines are maintained in fully defined serum-free, steroid-free mediums. The cells of the invention, as exemplified by NCI-H295 cells, express all of the major pathways of steroid-ogenesis, including formation of corticosteroids, mineralocorticoids and androgens.
摘要翻译：已经建立了肾上腺皮质癌的连续细胞系。将细胞系维持在完全限定的无血清，无类固醇的培养基中。本发明的细胞，如NCI-H295细胞所示，表达类固醇发生的所有主要途径，包括皮质类固醇，盐皮质激素和雄激素的形成。

5. 发明授权

US5173509A Suramin and active analogues thereof in the treatment of hypercalcemia 失效
标题翻译：苏氨酸及其活性类似物治疗高钙血症
公开(公告)号：US5173509A
公开(公告)日：1992-12-22
申请号：US500913
申请日：1990-03-29
申请人： McClellan M. Walther , Renato V. LaRocca , Charles E. Myers , Cy A. Stein , W. Marston Linehan
发明人： McClellan M. Walther , Renato V. LaRocca , Charles E. Myers , Cy A. Stein , W. Marston Linehan
IPC分类号： A61K31/185
CPC分类号： A61K31/185
摘要： A method is disclosed for the treatment of hypercalcemia in a patient, by administering to the patient an effective amount of suramin, or an active analogue thereof, for lowering calcium plasma levels in the patient. Human data shows a single course of treatment lowers plasma calcium levels to normal for three months.
摘要翻译：公开了一种用于治疗患者高钙血症的方法，通过向患者施用有效量的苏氨敏素或其活性类似物以降低患者体内的钙血浆水平。人类数据显示，单次疗程可使血浆钙水平降低至正常水平三个月。

6. 发明授权

US5158940A Use of suramin to treat rheumatologic diseases 失效
标题翻译：使用SURAMIN治疗感冒性疾病
公开(公告)号：US5158940A
公开(公告)日：1992-10-27
申请号：US479817
申请日：1990-02-14
申请人： Renato V. LaRocca , Cy A. Stein , Michael R. Cooper , Charles E. Myers
发明人： Renato V. LaRocca , Cy A. Stein , Michael R. Cooper , Charles E. Myers
IPC分类号： A61K31/185 , A61K31/17 , A61K31/715 , A61P29/00 , A61P37/06
CPC分类号： A61K31/715 , A61K31/17
摘要： Polysulfonated compounds such as suramin are used to treat immunoregulatoryisorders. Particular use in the treatment of rheumatologic diseases such as rheumatoid arthritis is shown.
摘要翻译：多磺化合物如苏拉明用于治疗免疫调节性疾病。显示了治疗类风湿性关节炎风湿病的特殊用途。

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