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1. 发明申请

WO1992003139A1 OLIGONUCLEOTIDE MODULATION OF CELL ADHESION 审中-公开
标题翻译：细胞粘附的寡糖调节
公开(公告)号：WO1992003139A1
公开(公告)日：1992-03-05
申请号：PCT/US1991005209
申请日：1991-07-23
申请人： ISIS PHARMACEUTICALS, INC. , BENNETT, Clarence, Frank , MIRABELLI, Christopher, K.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： C12N15/1138 , A61K38/00 , C07K14/705 , C12N2310/315 , C12N2310/322 , C12N2310/3521 , C12N2310/3531 , C12N2310/3533
摘要： 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.
摘要翻译：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。

2. 发明申请

WO1991016901A1 OLIGONUCLEOTIDE MODULATION OF ARACHIDONIC ACID METABOLISM 审中-公开
标题翻译：阿昔洛韦酸代谢的寡糖调节
公开(公告)号：WO1991016901A1
公开(公告)日：1991-11-14
申请号：PCT/US1991002628
申请日：1991-04-17
申请人： ISIS PHARMACEUTICALS, INC. , BENNETT, Clarence, Frank , ECKER, David, J. , CROOKE, Stanely, T. , MIRABELLI, Christopher, K.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： C12N15/1137 , C12N9/0006 , C12N2310/15 , C12N2310/315 , C12Q1/68 , C12Q1/6839 , C12Q1/6883 , C12Q2600/158 , C12Y113/11012 , C12Y301/01004 , C12Y301/04003 , C12Y303/02006 , G01N33/88
摘要： 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.
摘要翻译：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。

3. 发明申请

WO1993020095A1 ANTISENSE OLIGONUCLEOTIDE INHIBITION OF PAPILLOMAVIRUS 审中-公开
标题翻译：抗原寡核苷酸抑制斑马鱼
公开(公告)号：WO1993020095A1
公开(公告)日：1993-10-14
申请号：PCT/US1993003075
申请日：1993-03-31
申请人： ISIS PHARMACEUTICALS, INC. , CROOKE, Stanley, T. , MIRABELLI, Christopher, K. , ECKER, David, J. , COWSERT, Lex, M.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H21/04
CPC分类号： C12N15/1131 , A61K38/00 , C07K14/005 , C12N2310/315 , C12N2710/20022 , C12Q1/6883 , C12Q1/70 , C12Q1/708
摘要： Oligonucleotides are provided which are capable of antisense interaction with messenger RNA of papillomavirus. Such oligonucleotides or oligonucleotide analogs can be used for diagnostics and therapeutics as well as for research purposes. In accordance with preferred embodiments of this invention, oligonucleotides are provided which are hybridizable with selected messenger RNA from a human papillomavirus. The oligonucleotide is able to inhibit the function of the RNA, and accordingly is useful for therapy for infections by such papillomavirus. In accordance with a preferred embodiment, portions of the papillomavirus are targeted for antisense attack. Thus, oligonucleotides are preferably provided which hybridize with the E2, E6 and E7 messenger RNAs.
摘要翻译：提供能够与乳头瘤病毒的信使RNA反义相互作用的寡核苷酸。这样的寡核苷酸或寡核苷酸类似物可用于诊断和治疗以及用于研究目的。根据本发明的优选实施方案，提供可与来自人乳头瘤病毒的选定信使RNA杂交的寡核苷酸。寡核苷酸能够抑制RNA的功能，因此可用于由这种乳头瘤病毒感染的治疗。根据优选实施方案，乳头瘤病毒的一部分被靶向用于反义攻击。因此，优选提供与E2，E6和E7信使RNA杂交的寡核苷酸。

4. 发明申请

WO1991012811A1 OLIGONUCLEOTIDE THERAPIES FOR MODULATING THE EFFECTS OF HERPESVIRUSES 审中-公开
标题翻译：用于调节HERPESVIRUSES的作用的寡核苷酸治疗
公开(公告)号：WO1991012811A1
公开(公告)日：1991-09-05
申请号：PCT/US1991001327
申请日：1991-02-25
申请人： ISIS PHARMACEUTICALS, INC. , DRAPER, Kenneth, G. , ECKER, David, J. , MIRABELLI, Christopher, K. , CROOKE, Stanley, T.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： C12N15/1133 , A61K38/00 , C07K14/005 , C12N2310/3125 , C12N2310/315 , C12N2710/16622
摘要： Compositions and methods are provided for the treatment and diagnosis of herpesvirus infections. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with RNA or DNA deriving from a gene corresponding to one of the open reading frames UL5, UL8, UL9, UL13, UL29, UL30, UL39, UL40, UL42, and UL52 of herpes simplex virus type 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 translation initiation site; it is also preferred that they comprise the sequence CAT. Methods of treating animals suspected of being infected with herpesvirus comprising contacting the animal with an oligonucleotide specifically hybridizable with RNA or DNA deriving from one of the foregoing genes of the herpesvirus are disclosed. Methods for treatment of infections caused by herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, human herpes virus 6, Epstein Barr virus or varicella zoster virus are disclosed.

5. 发明申请

WO1991008313A1 ANTISENSE OLIGONUCLEOTIDE INHIBITION OF PAPILLOMAVIRUS 审中-公开
标题翻译：抗原寡核苷酸抑制斑马鱼
公开(公告)号：WO1991008313A1
公开(公告)日：1991-06-13
申请号：PCT/US1990007067
申请日：1990-12-03
申请人： ISIS PHARMACEUTICALS, INC. , CROOKE, Stanley, T. , MIRABELLI, Christopher, K. , ECKER, David, J. , COWSERT, Lex, M.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C12Q01/70
CPC分类号： C12N15/1131 , A61K38/00 , C07K14/005 , C12N2310/315 , C12N2710/20022 , C12Q1/6883 , C12Q1/70 , C12Q1/708
摘要： Oligonucleotides and oligonucleotide analogs are provided which are capable of antisense interaction with messenger RNA of papillomavirus. Such oligonucleotides or oligonucleotide analogs can be used for diagnostics and therapeutics as well as for research purposes. In accordance with preferred embodiments of this invention, oligonucleotide or oligonucleotide analog is provided which is hybridizable with a messenger RNA from a papillomavirus. The oligonucleotide or oligonucleotide analog is able to inhibit the function of the RNA, and accordingly is useful for therapy for infections by such papillomavirus. In accordance with a preferred embodiment, portions of the papillomavirus are targeted for antisense attack. Thus oligonucleotides are preferably provided which hybridize with the E2, E1, E7, or E6-7 messenger RNAs.
摘要翻译：提供寡核苷酸和寡核苷酸类似物，其能够与乳头瘤病毒的信使RNA反义相互作用。这样的寡核苷酸或寡核苷酸类似物可用于诊断和治疗以及用于研究目的。根据本发明的优选实施方案，提供可与来自乳头瘤病毒的信使RNA杂交的寡核苷酸或寡核苷酸类似物。寡核苷酸或寡核苷酸类似物能够抑制RNA的功能，因此可用于由这种乳头瘤病毒感染的治疗。根据优选实施方案，乳头瘤病毒的一部分被靶向用于反义攻击。因此优选提供与E2，E1，E7或E6-7信使RNA杂交的寡核苷酸。

6. 发明申请

WO1995004749A1 OLIGOMERS FOR MODULATING METABOLIC FUNCTION 审中-公开
标题翻译：用于调节代谢功能的低分子
公开(公告)号：WO1995004749A1
公开(公告)日：1995-02-16
申请号：PCT/US1994009026
申请日：1994-08-05
申请人： ISIS PHARMACEUTICALS, INC. , BENNETT, Clarence, F. , MIRABELLI, Christopher, K.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H21/04
CPC分类号： C12N15/1138 , C12N2310/3181 , C12Q1/6876 , C12Q2600/158
摘要： Oligomers useful for modulating metabolic processes are disclosed, for example oligomers directed against Human Intercellular Adhesion Molecule-1 (ICAM-1). These oligomers are comprised of subunits, at least one of which is a protein nucleic acid subunit. Therapeutic and diagnostic methods are also provided.
摘要翻译：公开了可用于调节代谢过程的低聚物，例如针对人细胞间粘附分子-1（ICAM-1）的寡聚体。这些寡聚体由亚基组成，其中至少一个是蛋白质核酸亚基。还提供了治疗和诊断方法。

7. 发明申请

WO1995004748A1 OLIGOMERS FOR MODULATING VIRAL PROCESSES 审中-公开
标题翻译：调解病毒过程的低级别人员
公开(公告)号：WO1995004748A1
公开(公告)日：1995-02-16
申请号：PCT/US1994009039
申请日：1994-08-09
申请人： ISIS PHARMACEUTICALS, INC. , ANDERSON, Kevin, P. , CROOKE, Stanley, T. , MIRABELLI, Christopher, K. , ECKER, David, J. , COWSERT, Lex, M.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H21/00
CPC分类号： C07H21/00 , C07K14/001 , C07K14/005 , C12N2710/16722 , C12N2710/20022
摘要： The present invention provides oligomers useful for modulating viral processes such as cytomegalovirus and papillomaviruses. The oligomers are comprised of subunits, at least one of which is a protein nucleic acid subunit. Therapeutic and diagnostic methods are also provided.
摘要翻译：本发明提供了可用于调节病毒过程例如巨细胞病毒和乳头瘤病毒的低聚物。寡聚体由亚基组成，其中至少一个是蛋白质核酸亚基。还提供了治疗和诊断方法。

8. 发明申请

WO1995010938A1 OLIGONUCLEOTIDE MODULATION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 审中-公开
标题翻译：多重耐药相关蛋白的寡核苷酸调节
公开(公告)号：WO1995010938A1
公开(公告)日：1995-04-27
申请号：PCT/US1994010827
申请日：1994-09-23
申请人： ISIS PHARMACEUTICALS, INC. , BARACCHINI, Edgardo, Jr. , BENNETT, Clarence, Frank
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A01N43/04
CPC分类号： C12N15/1138 , A61K38/00 , C07H21/00 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3517 , C12N2310/3527 , C12N2310/3521
摘要： Compositions and methods are provided for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of the synthesis or metabolism of multidrug resistance-associated protein (MRP). In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding multidrug resistance-associated protein (MRP). Methods of treating animals suffering from diseases or conditions amenable to therapeutic intervention by modulating multidrug resistance with an oligonucleotide specifically hybridizable with RNA or DNA corresponding to multidrug resistance-associated protein (MRP) are disclosed. Methods of preventing the development of multidrug resistance and of improving the efficacy of chemotherapy are also disclosed.
摘要翻译：提供组合物和方法用于治疗和诊断适于通过调节多药耐药相关蛋白（MRP）的合成或代谢来治疗的疾病或病症。根据优选实施方案，提供了与编码多药耐药相关蛋白（MRP）的核酸特异性杂交的寡核苷酸。公开了通过用与多药耐药相关蛋白（MRP）相应的RNA或DNA特异性杂交的寡核苷酸调节多药耐药性来治疗患有治疗性干预的疾病或病症的动物的方法。还公开了预防多药耐药性发展和提高化学疗效的方法。

9. 发明申请

WO1993007883A1 DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES 审中-公开
标题翻译：具有改进的摄取和其他性质的衍生的寡核苷酸
公开(公告)号：WO1993007883A1
公开(公告)日：1993-04-29
申请号：PCT/US1992009196
申请日：1992-10-23
申请人： ISIS PHARMACEUTICALS, INC. , MANOHARAN, Muthiah , COOK, Philip, Dan , BENNETT, Clarence, Frank
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： C07H21/00 , C07H23/00 , C07J43/003 , C07J51/00
摘要： 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.
摘要翻译：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。

10. 发明申请

WO1993017125A1 OLIGONUCLEOTIDE MODULATION OF CELL GROWTH 审中-公开
标题翻译：细胞生长的寡核苷酸调节
公开(公告)号：WO1993017125A1
公开(公告)日：1993-09-02
申请号：PCT/US1993000754
申请日：1993-01-27
申请人： BAYLOR COLLEGE OF MEDICINE , ISIS PHARMACEUTICALS, INC. , BUSCH, Harris , BENNETT, Clarence, Frank , PERLAKY, Laszlo , SAIJO, Yasuo , BUSCH, Rose, K.
发明人： BAYLOR COLLEGE OF MEDICINE , ISIS PHARMACEUTICALS, INC.
IPC分类号： C12Q01/68
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/3521 , C12Q1/6886 , C12Q2600/136
摘要： Oligonucleotides capable of inhibiting the production of proliferation associated proteins are provided. Oligonucleotides designed to be hybridizable with nucleic acids encoding nucleolar proteins are believed to be therapeutically useful. Certain of such oligonucleotides, hybridizable to portions of the gene coding for p120, especially the 3' untranslated region, were made and found to inhibit the synthesis of p120. The oligonucleotides of the invention are useful for the treatment of diseases characterized by hyperproliferation of cells such as malignancies, inflammatory and cardiovascular diseases. Treatment of human breast cell carcinoma, human epitheloid cervix carcinoma, human amelanotic malanoma and human renal cell carcinoma and other tumors are indicated.
摘要翻译：提供能够抑制增殖相关蛋白产生的寡核苷酸。设计为可与编码核仁蛋白的核酸杂交的寡核苷酸被认为是治疗上有用的。制备了与编码p120的基因的部分杂交的某些这样的寡核苷酸，特别是3'非翻译区，发现抑制p120的合成。本发明的寡核苷酸可用于治疗特征为细胞过度增殖的疾病，例如恶性肿瘤，炎性和心血管疾病。表明人乳腺癌细胞癌，人类上皮细胞癌宫颈癌，人类无黑色素瘤恶性肿瘤和人肾细胞癌等肿瘤的治疗。

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