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    Derivatized oligonucleotides having improved uptake and other properties
    2.
    发明申请
    Derivatized oligonucleotides having improved uptake and other properties 失效
    具有改善摄取和其他性质的衍生寡核苷酸

    公开(公告)号：US20050043219A1

    公开(公告)日：2005-02-24

    申请号：US10755166

    申请日：2004-01-09

    申请人： Muthiah Manoharan ,  Phillip Cook ,  Clarence Bennett

    发明人： Muthiah Manoharan ,  Phillip Cook ,  Clarence Bennett

    IPC分类号： A61K38/16 ,  A61K48/00 ,  C07H21/04 ,  C07J1/00 ,  C07J17/00 ,  C07K14/47 ,  C12Q1/68 ,  H04L12/42 ,  H04L12/46 ,  H04L12/56 ,  H04Q11/04

    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。

    Compositions and methods for non-parenteral delivery of oligonucleotides
    4.
    发明申请
    Compositions and methods for non-parenteral delivery of oligonucleotides 有权
    用于非肠胃外递送寡核苷酸的组合物和方法

    公开(公告)号：US20070249551A1

    公开(公告)日：2007-10-25

    申请号：US11237063

    申请日：2005-09-28

    申请人： Ching-Leou Teng ,  Phillip Cook ,  Lloyd Tillman ,  Gregory Hardee ,  David Ecker ,  Muthiah Manoharan

    发明人： Ching-Leou Teng ,  Phillip Cook ,  Lloyd Tillman ,  Gregory Hardee ,  David Ecker ,  Muthiah Manoharan

    IPC分类号： A61K48/00

    CPC分类号： A61K48/0008 ,  A61K9/0014 ,  A61K9/0031 ,  A61K9/107 ,  A61K9/1075 ,  A61K38/00 ,  A61K47/12 ,  A61K47/28 ,  A61K48/00 ,  A61K48/0025 ,  A61K48/0041 ,  C12N15/113 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3521 ,  C12N2310/3527 ,  C12N2310/3525

    摘要： The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes. The compositions and methods of the invention are utilized to effect the oral, buccal, rectal or vaginal administration of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic, palliative or prophylactic purposes

    摘要翻译： 本发明涉及通过非肠胃外给药途径增强寡核苷酸和核酸的局部和全身摄取和递送的组合物和方法。 包含本文公开的寡核苷酸的药物组合物包括用于全身递送的乳液和微乳液制剂用于各种应用和口服剂型。 还令人惊讶地发现，可以用简单的溶液，例如纯的或盐水，通过直肠灌肠剂和栓剂将寡核苷酸局部递送至结肠部位。 寡核苷酸的这种药物组合物可以进一步包括一种或多种用于将寡核苷酸和其它核酸转移穿过粘膜的渗透增强剂。 本发明的组合物和方法用于对动物进行口服，口腔，直肠或阴道给予反义寡核苷酸，以调节动物中基因的表达用于调查，治疗，姑息或预防目的

    Oligonucleotdies having A-DNA form and B-DNA form conformational geometry
    5.
    发明申请
    Oligonucleotdies having A-DNA form and B-DNA form conformational geometry 审中-公开
    具有A-DNA形式和B-DNA的寡核苷酸形成构象几何

    公开(公告)号：US20070123702A1

    公开(公告)日：2007-05-31

    申请号：US11283119

    申请日：2005-11-17

    申请人： Muthiah Manoharan ,  Venkatraman Mohan ,  Phillip Cook ,  Andrew Kawasaki

    发明人： Muthiah Manoharan ,  Venkatraman Mohan ,  Phillip Cook ,  Andrew Kawasaki

    IPC分类号： C07H21/02

    CPC分类号： C07H21/00 ,  C07H19/04 ,  C07H19/20 ,  C07H21/02

    摘要： Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2′ endo sugars or O4′ endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2′-O-modified nucleotides that have 3′ endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.

    摘要翻译： 公开了含有A型构象几何形状和B-构象几何核苷酸的修饰寡核苷酸。 当结合到靶核酸链上时，B型几何允许寡核苷酸用作核糖核酸酶H的底物。 A型几何赋予调节结合亲和力和核酸酶抗性的寡核苷酸的性质。 通过使用C2'内糖或O4'内糖，B型特征被赋予寡核苷酸的一部分。 通过使用具有3'内部几何形状的2'-O-修饰的核苷酸或使用具有特定核酸酶稳定性的端帽或通过使用它们彼此结合来赋予A型特征。

    Car rim protector
    9.
    外观设计
    Car rim protector 失效
    汽车保护罩

    公开(公告)号：USD491874S1

    公开(公告)日：2004-06-22

    申请号：US29196342

    申请日：2003-12-29

    申请人： Phillip Cook

    设计人： Phillip Cook