公开(公告)号：WO1993018052A1

公开(公告)日：1993-09-16

申请号：PCT/US1993002059

申请日：1993-03-05

Applicant: ISIS PHARMACEUTICALS, INC. ,  COOK, Phillip, Dan ,  MANOHARAN, Muthian ,  BRUICE, Thomas

Inventor： ISIS PHARMACEUTICALS, INC.

IPC: C07H21/04

CPC classification number: C07H21/00

Abstract: Covalent cross-linkages for two oligonucleotide strands or for first and second regions of a single oligonucleotide strand connect sugar moieties of nucleotides on the respective strands or the regions of the single strand. The cross-linkages are connected to at least one strand or region via a space-spanning group. The cross-linkage also can be connected to the other strand or other region via a space-spanning group or via an abasic site located on the other strand or other region.

Abstract translation: 将两条寡核苷酸链或单个寡核苷酸链的第一和第二区的共价交联连接在相应链或单链的区域上的核苷酸的糖部分。 交联通过空间跨越组连接到至少一个链或区域。 交联也可以经由跨越太空的组或通过位于另一股或其他区域上的无碱基位点连接到另一条链或其它区。

公开(公告)号：WO1993004204A1

公开(公告)日：1993-03-04

申请号：PCT/US1992007121

申请日：1992-08-21

Applicant: ISIS PHARMACEUTICALS, INC. ,  ECKER, David, J. ,  WYATT, Jacqueline ,  BRUICE, Thomas, W. ,  ANDERSON, Kevin ,  HANECAK, Ronnie, C. ,  VICKERS, Timothy ,  DAVIS, Peter

Inventor： ISIS PHARMACEUTICALS, INC.

IPC: C12Q01/68

CPC classification number: G01N33/5308 ,  C12Q1/6811 ,  C12Q1/6827 ,  C12Q1/6853 ,  C12Q1/686 ,  C12Q1/6869 ,  C12Q1/70 ,  C12Q2537/143

Abstract: Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled subunits are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.

Abstract translation: 提供了可用于测定从主要随机组装的亚基池中对靶分子具有比活性的低聚物的方法。 所公开的方法涉及重复合成越来越简单的低聚体组合，以及用于确定具有最高活性的寡聚体的选择程序。 不使用酶允许将这些方法应用于可以以受控方式低聚的任何分子。

公开(公告)号：WO1993005182A1

公开(公告)日：1993-03-18

申请号：PCT/US1992007489

申请日：1992-09-04

Applicant: ISIS PHARMACEUTICALS, INC. ,  BRUICE, Thomas, W.

Inventor： ISIS PHARMACEUTICALS, INC.

IPC: C12Q01/68

CPC classification number: A61K31/70 ,  C12Q1/6811

Abstract: Oligonucleotides which selectively bind to target biomolecules may be determined by in vitro assay of a pool of random oligonucleotides for activity against said biomolecules, followed by recovery and characterization of selected oligonucleotides. Oligonucleotides so determined may be utilized for therapeutic, diagnostic and research reagent purposes.

Abstract translation: 选择性结合靶生物分子的寡核苷酸可以通过体外测定随机寡核苷酸库来测定针对所述生物分子的活性，随后恢复和表征所选择的寡核苷酸。 如此确定的寡核苷酸可用于治疗，诊断和研究试剂目的。

公开(公告)号：WO1991014436A1

公开(公告)日：1991-10-03

申请号：PCT/US1991001822

申请日：1991-03-19

Applicant: ISIS PHARMACEUTICALS, INC. ,  ECKER, David, J. ,  BRUICE, Thomas, W. ,  VICKERS, Timothy, A.

Inventor： ISIS PHARMACEUTICALS, INC.

IPC: A61K31/70

CPC classification number: A61K31/70 ,  A61K31/7105 ,  A61K38/00 ,  C07H21/00 ,  C07K14/005 ,  C12N15/1132 ,  C12N15/67 ,  C12N15/85 ,  C12N2310/13 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2740/16322 ,  C12Q1/68 ,  C12Q1/6897 ,  C12Q1/703 ,  C12N2310/3521

Abstract: Expression of genes may be modulated by employment of compositions which are capable of RNA mimicry. A portion of RNA coded by the gene whose expression is to be modulated is selected which is capable of interacting with one or more proteins. An oligonucleotide or oligonucleotide analog is then prepared in such a way as to mimic the portion of the RNA. Cells containing the gene are then contacted with the oligonucleotide or oligonucleotide analog to effect the modulation. Therapeutic compositions and methods, especially for the treatment of human immunodeficiency, are disclosed.

Abstract translation: 可以通过使用能够进行RNA模拟的组合物来调节基因的表达。 选择由其表达被调节的基因编码的RNA的一部分，其能够与一种或多种蛋白质相互作用。 然后制备寡核苷酸或寡核苷酸类似物，以模拟RNA的部分。 然后将含有该基因的细胞与寡核苷酸或寡核苷酸类似物接触以进行调节。 公开了治疗组合物和方法，特别是用于治疗人类免疫缺陷。

公开(公告)号：WO1993017717A1

公开(公告)日：1993-09-16

申请号：PCT/US1993002057

申请日：1993-03-05

Applicant: ISIS PHARMACEUTICALS, INC. ,  COOK, Phillip, Dan ,  BRUICE, Thomas ,  GUINOSSO, Charles, John ,  KAWASAKI, Andrew, Mamoru ,  GRIFFEY, Richard

Inventor： ISIS PHARMACEUTICALS, INC.

IPC: A61K48/00

CPC classification number: C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C07K14/005 ,  C12N9/0069 ,  C12N15/1137 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3511 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12N2740/16322 ,  C12Q1/68 ,  C12Q1/6813 ,  C12Y113/11012

Abstract: Compositions and methods for modulating the activity of RNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.

Abstract translation: 公开了调节RNA活性的组合物和方法。 根据优选实施方案，制备包含靶向和反应部分的反义组合物。 反应性部分优选包含通过具有或不具有插入插入部分的接头与靶向寡核苷酸缀合的一个或两个咪唑官能团。 还公开了治疗学，诊断和研究方法，合成核苷和可以被制成寡核苷酸的核苷片段也是公开的。