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1. 发明申请

WO1995006659A1 AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES 审中-公开
标题翻译：胺衍生的核苷酸和寡核苷酸
公开(公告)号：WO1995006659A1
公开(公告)日：1995-03-09
申请号：PCT/US1994010131
申请日：1994-09-02
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , MANOHARAN, Muthiah , GUINOSSO, Charles, J.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H21/00
CPC分类号： C12N15/113 , A61K47/51 , C07H19/04 , C07H19/16 , C07H19/20 , C07H21/00 , C12N15/1131 , C12N15/1132 , C12N15/1133 , C12N15/1135 , C12N15/1138 , C12N2310/315 , C12N2310/318 , C12N2310/32 , C12N2310/321 , C12N2310/3527
摘要： Nucleosides and oligonucleosides functionalized to include alkylamino functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the alkylamino group.
摘要翻译：功能化为包括烷基氨基官能团的核苷和寡核苷酸及其衍生物。在某些实施方案中，本发明的化合物还包括通过烷基氨基连接到核苷上的类固醇，报道分子，报道酶，亲脂性分子，肽或蛋白质。

2. 发明申请

WO1996030377A1 NITROGENOUS MACROCYCLIC COMPOUNDS 审中-公开
标题翻译：硝基大环化合物
公开(公告)号：WO1996030377A1
公开(公告)日：1996-10-03
申请号：PCT/US1996004215
申请日：1996-03-27
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , AN, Haoyun , GUINOSSO, Charles, J. , KUNG, Pei-Pei , FRASER, Allister, S.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07D519/00
CPC分类号： C07D471/08 , B01J2219/0072 , C07D515/08
摘要： Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring sytem. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.
摘要翻译：构建新的大环化合物以包括被至少一个环系中断的大环状结构。每个中断环系统包括两个桥头原子。桥头原子键合到一个或多个互连一个或多个环系统的桥，从而形成大的环状结构。位于每个桥中的是具有化学官能团衍生化的两个或多个含氮部分。环系统可以包括作为环原子的另外的含氮部分或连接到环上的侧基上。这些也可以用化学官能团衍生化。化学官能团的总体对大环化合物赋予某些构象和其他性质。根据本发明的某些实施方案，利用化学官能团和含氮部分的置换和组合来制备这种大环化合物的文库，从而构建文库的复杂性。

3. 发明申请

WO1995021184A1 SUBSTITUTED PURINES AND OLIGONUCLEOTIDE CROSS-LINKING 审中-公开
标题翻译：替代产品和寡糖交联
公开(公告)号：WO1995021184A1
公开(公告)日：1995-08-10
申请号：PCT/US1995001361
申请日：1995-02-01
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , MANOHARAN, Muthiah , RAMASAMY, Kanda, S.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H19/16
CPC分类号： C07H19/16 , A61K38/00 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C07K14/005 , C12N9/0069 , C12N15/113 , 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
摘要： This invention is directed to novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents -- agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The compounds of the invention may also be used for cross-linking oligonucleotides. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating deseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要翻译：本发明涉及用于包含在寡核苷酸中的新型基于嘌呤的化合物。当掺入寡核苷酸时，本发明的化合物特别可用作“反义”试剂 - 能够与RNA的核苷酸序列特异性杂交的试剂。本发明的化合物也可用于交联寡核苷酸。寡核苷酸用于各种治疗和诊断目的，例如治疗疾病，调节实验系统中的基因表达，通过使用与这种RNA的反义相互作用来测定RNA和RNA产物，诊断疾病，调节蛋白质的产生，并在现场具体时尚中切割RNA。本发明的化合物包括新的杂环碱基，核苷和核苷酸。当掺入寡核苷酸时，本发明的化合物可用于调节RNA的活性。

4. 发明申请

WO1993017717A1 COMPOSITIONS AND METHODS FOR MODULATING RNA 审中-公开
标题翻译：用于调节RNA的组合物和方法
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
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , BRUICE, Thomas , GUINOSSO, Charles, John , KAWASAKI, Andrew, Mamoru , GRIFFEY, Richard
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A61K48/00
CPC分类号： 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
摘要： 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.
摘要翻译：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。

5. 发明申请

WO1998005332A1 NOVEL HETEROCYCLE COMPOSITIONS 审中-公开
标题翻译：新型杂环化合物
公开(公告)号：WO1998005332A1
公开(公告)日：1998-02-12
申请号：PCT/US1997013686
申请日：1997-08-01
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , KAWASAKI, Andrew, M. , KUNG, Pei, Pei
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： A61K31/495
CPC分类号： C07D295/13 , A61K31/495 , A61K31/496 , C07D261/08 , C07D277/82 , C07D295/15 , C40B40/00 , Y02A50/473 , A61K2300/00
摘要： Compositions comprising novel di-nitrogen heterocycle compounds containing at least one N-meta-substituted alkaryl group and/or novel meta-benzylic compounds. The compounds of the present invention are useful as antibacterial and as other pharmaceutical agents and as intermediates for preparation of other pharmaceutical agents. In addition, compounds of the present invention are useful as research reagents.
摘要翻译：包含含有至少一个N-间位取代的烷芳基的新型二氮杂环化合物和/或新的间 - 苄基化合物的组合物。本发明的化合物可用作抗细菌剂和其他药剂以及用于制备其它药剂的中间体。此外，本发明的化合物可用作研究试剂。

6. 发明申请

WO1993013121A1 GAPPED 2' MODIFIED OLIGONUCLEOTIDES 审中-公开
标题翻译： GAPPED 2'MODIFIED OLIGONUCLEOTIDES
公开(公告)号：WO1993013121A1
公开(公告)日：1993-07-08
申请号：PCT/US1992011339
申请日：1992-12-23
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H21/04
CPC分类号： C12Q1/6813 , C07H21/00 , C07H21/04 , C07K14/003 , C07K14/82 , C12N15/1135 , C12N2310/315 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/3521 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533 , C12Q1/6816 , C12Q1/6832 , C12Q2525/125 , C12Q2521/319 , C12Q2525/101
摘要： Oligonucleotides and other macromolecules are provided that have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strand, and subsequences of 2'-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H enzyme. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to antisense therapeutics.
摘要翻译：提供具有增加的核酸酶抗性的寡核苷酸和其它大分子，用于增加对互补链的结合亲和力的取代基，以及激活核糖核酸酶H酶的2'-脱氧 - 赤 - 戊呋喃糖基核苷酸的亚序列。这样的寡核苷酸和大分子可用于诊断和其他研究目的，用于调节生物体中的蛋白质，以及诊断，检测和治疗对反义治疗剂敏感的其它病症。

7. 发明申请

WO1992020822A1 BACKBONE MODIFIED OLIGONUCLEOTIDE ANALOGUES 审中-公开
标题翻译：反向修饰的寡核苷酸类似物
公开(公告)号：WO1992020822A1
公开(公告)日：1992-11-26
申请号：PCT/US1992004294
申请日：1992-05-21
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , SANGHVI, Yogesh, Shantilal , VASSEUR, Jean-Jacques , DEBART, Françoise
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C12Q01/68
CPC分类号： C07D405/04 , A61K47/549 , A61K47/59 , C07D405/14 , C07F7/1804 , C07H11/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Therapeutic oligonucleotide analogs which have nuclease resistance and improved cellular uptake are provided. Replacement of posphorodiester inter-sugar linkages found in wild type oligomers with four atom linking groups forms unique di- and polynucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.
摘要翻译：提供具有核酸酶抗性和改善的细胞摄取的治疗性寡核苷酸类似物。在具有四个原子连接基团的野生型寡聚物中发现的磷酸酯间糖链的替换形成用于调节RNA表达和治疗学的独特的二核苷酸和多核苷和核苷酸。还公开了合成和使用方法。

8. 发明申请

WO1998010286A1 METHODS FOR PROCESSING CHEMICAL COMPOUNDS HAVING REACTIVE FUNCTIONAL GROUPS 审中-公开
标题翻译：用于处理具有反应性功能团的化学化合物的方法
公开(公告)号：WO1998010286A1
公开(公告)日：1998-03-12
申请号：PCT/US1997015493
申请日：1997-09-04
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： G01N33/53
CPC分类号： C07D471/08 , C07C231/02 , C07C269/04 , C07C269/06 , C40B40/04 , C40B50/08 , G01N33/5308 , C07C233/36 , C07C271/20
摘要： Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring sytem. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.
摘要翻译：构建新的大环化合物以包括被至少一个环系中断的大环状结构。每个中断环系统包括两个桥头原子。桥头原子键合到一个或多个互连一个或多个环系统的桥，从而形成大的环状结构。位于每个桥中的是具有化学官能团衍生化的两个或多个含氮部分。环系统可以包括作为环原子的另外的含氮部分或连接到环上的侧基上。这些也可以用化学官能团衍生化。化学官能团的总体对大环化合物赋予某些构象和其他性质。根据本发明的某些实施方案，利用化学官能团和含氮部分的置换和组合来制备这种大环化合物的文库，从而构建文库的复杂性。

9. 发明申请

WO1993018052A1 COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES 审中-公开
标题翻译：共同交叉的寡核苷酸
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
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , MANOHARAN, Muthian , BRUICE, Thomas
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： C07H21/04
CPC分类号： C07H21/00
摘要： 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.
摘要翻译：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。

10. 发明申请

WO1998008091A1 NORMALIZATION OF COMBINATORIAL REACTIONS 审中-公开
标题翻译：组合反应的正规化
公开(公告)号：WO1998008091A1
公开(公告)日：1998-02-26
申请号：PCT/US1997014144
申请日：1997-08-22
申请人： ISIS PHARMACEUTICALS, INC. , COOK, Phillip, Dan , GAUS, Hans , CUMMINS, Lendell, L.
发明人： ISIS PHARMACEUTICALS, INC.
IPC分类号： G01N33/53
CPC分类号： C07K1/047
摘要： Improvements in the provision of combinatorial chemical libraries are provided. In accordance with preferred embodiments, sets of chemical reactants are normalized to ensure representations of all anticipated reaction products in a reaction between the set and a scaffold molecule. The processes can be practiced iteratively to yield large libraries.
摘要翻译：提供了提供组合化学图书馆的改进。根据优选的实施方案，将化学反应物组归一化以确保所述预期反应产物在组和支架分子之间的反应中的表示。这些过程可以迭代地实现以产生大的库。

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