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51. 发明申请

US20050026160A1 Compositions comprising alternating 2'-modified nucleosides for use in gene modulation 有权
公开(公告)号：US20050026160A1
公开(公告)日：2005-02-03
申请号：US10701007
申请日：2003-11-04
申请人： Charles Allerson , Balkrishen Bhat , Anne Eldrup , Muthiah Manoharan , Richard Griffey , Brenda Baker , Eric Swayze
发明人： Charles Allerson , Balkrishen Bhat , Anne Eldrup , Muthiah Manoharan , Richard Griffey , Brenda Baker , Eric Swayze
IPC分类号： C07H21/00 , C07H21/04 , C12N15/113 , C12Q1/68
CPC分类号： C07H21/00 , C07H21/04 , C12N15/111 , C12N15/113 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2310/343 , C12N2310/3521 , C12N2310/3533 , C12N2320/51
摘要： The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

52. 发明授权

US06831166B2 Derivatized oligonucleotides having improved uptake and other properties 失效
标题翻译：具有改善摄取和其他性质的衍生寡核苷酸
公开(公告)号：US06831166B2
公开(公告)日：2004-12-14
申请号：US10073718
申请日：2002-02-11
申请人： Muthiah Manoharan , Phillip Dan Cook , Clarence Frank Bennett
发明人： Muthiah Manoharan , Phillip Dan Cook , Clarence Frank Bennett
IPC分类号： C07H1900
CPC分类号： C07H21/04 , C07J1/00 , C12N2710/20022 , H04J2203/0042 , H04J2203/006
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 liked 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的核苷类为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。

53. 发明授权

US06803198B2 Carbamate-derivatized nucleosides and oligonucleosides 失效
标题翻译：氨基甲酸酯衍生的核苷和寡核苷
公开(公告)号：US06803198B2
公开(公告)日：2004-10-12
申请号：US09934138
申请日：2001-08-21
申请人： Phillip Dan Cook , Muthiah Manoharan
发明人： Phillip Dan Cook , Muthiah Manoharan
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07J1/00
摘要： Nucleosides and oligonucleosides functionalized to include carbamate 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 carbamate group.
摘要翻译：功能化为包括氨基甲酸酯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氨基甲酸酯基团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。

54. 发明授权

US06784290B1 Antisense oligonucleotide inhibition of ras 失效
标题翻译：反义寡核苷酸抑制ras
公开(公告)号：US06784290B1
公开(公告)日：2004-08-31
申请号：US09575554
申请日：2000-05-22
申请人： Brett P. Monia , Lex M. Cowsert , Muthiah Manoharan
发明人： Brett P. Monia , Lex M. Cowsert , Muthiah Manoharan
IPC分类号： C07H2102
CPC分类号： C12N15/1135 , A61K38/00 , C07K14/82 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/3521 , C12N2310/3527 , C12N2310/3533 , C12Q2525/125 , C12N2310/3525
摘要： Compositions and methods are provided for the modulation of ras expression. Oligonucleotides are provided which are targeted to nucleic acids encoding human ras. Oligonucleotides specifically hybridizable with mRNA encoding human H-ras, Ki-ras and N-ras are provided. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. Methods are also disclosed for modulating ras gene expression in cells and tissues using the oligonucleotides provided, and for specific modulation of expression of activated ras. Methods for diagnosis, detection and treatment of conditions, or particular cancers, associated with ras are also disclosed.
摘要翻译：提供了ras表达调控的组成和方法。提供了靶向编码人ras的核酸的寡核苷酸。提供与编码人H-ras，Ki-ras和N-ras的mRNA特异性杂交的寡核苷酸。这样的寡核苷酸可用于治疗和诊断以及用于研究目的。还公开了使用所提供的寡核苷酸调节细胞和组织中的ras基因表达以及用于特异性调节活化的ras表达的方法。还公开了与ras有关的病症或特定癌症的诊断，检测和治疗方法。

55. 发明授权

US06673912B1 2′-O-aminoethyloxyethyl-modified oligonucleotides 有权
标题翻译： 2'-O-氨基乙氧基乙基修饰的寡核苷酸
公开(公告)号：US06673912B1
公开(公告)日：2004-01-06
申请号：US10121135
申请日：2002-04-11
申请人： Muthiah Manoharan , Phillip Dan Cook
发明人： Muthiah Manoharan , Phillip Dan Cook
IPC分类号： C07H2100
CPC分类号： C12N15/113 , C07H21/00 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/3527
摘要： 2′-O-Modified ribosyl nucleosides and modified oligomeric compounds containing such nucleosidic monomers are disclosed. Oligomeric compounds are disclosed that have increased binding affinity as shown by molecular modeling experiments. The 2′-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3′ endo geometries.
摘要翻译：公开了2'-O-修饰的核糖基核苷和含有这种核苷单体的改性低聚化合物。公开了具有增强的结合亲和力的低聚化合物，如分子模拟实验所示。本发明的2'-O-修饰的核苷包括将核苷的糖部分优先置于3'内部几何形状的环结构。

56. 发明授权

US06525031B2 Targeted Oligonucleotide conjugates 有权
标题翻译：靶向寡核苷酸缀合物
公开(公告)号：US06525031B2
公开(公告)日：2003-02-25
申请号：US09934424
申请日：2001-08-21
申请人： Muthiah Manoharan
发明人： Muthiah Manoharan
IPC分类号： C12Q168
CPC分类号： C12N15/87
摘要： The present invention provides improved ingress of therapeutic and other moieties into cellular targets. In accordance with preferred embodiments, complexes are provided which carry primary moieties, chiefly therapeutic moieties, to such target cells. Such complexes preferably feature cell surface receptor ligands to provide specificity. Such ligands are preferably bound to primary moieties through polyfunctional manifold compounds.
摘要翻译：本发明提供治疗性和其它部分进入细胞靶的改善的进入。根据优选的实施方案，提供了将主要部分（主要是治疗性部分）携带到这些靶细胞的复合物。这样的复合物优选地具有细胞表面受体配体以提供特异性。这样的配体优选通过多官能歧管化合物与主要部分结合。

57. 发明授权

US06495671B1 Oligonucleotide and nucleotide amine analogs, methods of synthesis and use 失效
标题翻译：寡核苷酸和核苷酸类似物，合成和使用方法
公开(公告)号：US06495671B1
公开(公告)日：2002-12-17
申请号：US09689964
申请日：2000-10-12
申请人： Muthiah Manoharan , P. Dan Cook
发明人： Muthiah Manoharan , P. Dan Cook
IPC分类号： C07H2102
CPC分类号： C07H21/00 , C12Q1/6813
摘要： Novel amine compounds are provided by the present invention. Methods of preparing and using said novel amine compounds are also provided.
摘要翻译：本发明提供了新的胺化合物。还提供了制备和使用所述新型胺化合物的方法。

58. 发明授权

US06440943B1 Oligonucleotides having site specific chiral phosphorothioate internucleoside linkages 有权
标题翻译：具有位点特异性手性硫代磷酸酯核苷间键的寡核苷酸
公开(公告)号：US06440943B1
公开(公告)日：2002-08-27
申请号：US09352058
申请日：1999-07-14
申请人： Phillip Dan Cook , Muthiah Manoharan
发明人： Phillip Dan Cook , Muthiah Manoharan
IPC分类号： A61K3170
CPC分类号： C07H21/00 , C07H19/04
摘要： Novel chiral compounds that mimic and/or modulate the activity of wild-type nucleic acids are disclosed. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′, and the 3′-terminal internucleoside linkages are chirally Sp and internal internucleoside linkages are chirally Rp.
摘要翻译：公开了模拟和/或调节野生型核酸活性的新型手性化合物。通常，化合物是硫代磷酸酯寡核苷酸，其中5'和3'末端核苷间键是手性Sp，内部核苷间键是手性Rp。

59. 发明授权

US06414135B1 C3′-methylene hydrogen phosphonate monomers and related compounds 失效
标题翻译： C3'-亚甲基氢膦酸酯单体和相关化合物
公开(公告)号：US06414135B1
公开(公告)日：2002-07-02
申请号：US09349035
申请日：1999-07-07
申请人： Phillip Dan Cook , Haoyun An , Tingmin Wang , Muthiah Manoharan
发明人： Phillip Dan Cook , Haoyun An , Tingmin Wang , Muthiah Manoharan
IPC分类号： C07H2100
CPC分类号： C07H21/00 , C07H19/10
摘要： The present invention is directed to nucleoside monomers wherein the 3′-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylenephosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.
摘要翻译：本发明涉及其中3'-O原子被亚甲基代替的核苷单体。本发明还提供了包含多个这样的单体的低聚物，其通过亚甲基膦酸酯键连接。此外，提供了制备根据本发明的单体和低聚物的方法。

60. 发明授权

US06403779B1 Regioselective synthesis of 2′-O-modified nucleosides 失效
标题翻译： 2'-O-修饰核苷的区域选择性合成
公开(公告)号：US06403779B1
公开(公告)日：2002-06-11
申请号：US09227782
申请日：1999-01-08
申请人： Andrew M. Kawasaki , Allister S. Fraser , Muthiah Manoharan , P. Dan Cook , Thazha P. Prakash
发明人： Andrew M. Kawasaki , Allister S. Fraser , Muthiah Manoharan , P. Dan Cook , Thazha P. Prakash
IPC分类号： C07H2102
CPC分类号： C07H19/06 , C07H19/16
摘要： Methods for the regioselective alkylation at the 2′-hydroxy position over the 3′-hydroxy position of nucleosides and nucleoside analogs, forming 2′-O-ester modified compounds, are disclosed. Reduction and derivatization of the 2′-O-ester provides 2′-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.
摘要翻译：公开了在形成2'-O-酯改性化合物的核苷和核苷类似物的3'-羟基位置上2'-羟基位置选择性烷基化的方法。 2'-O-酯的还原和衍生化提供可用于合成具有改善的杂交亲和性和核酸酶抗性的寡聚化合物的2'-O-修饰的核苷和核苷类似物。

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