利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

100 条记录 (耗时 0.113 秒)

    Folate conjugates
    33.
    发明授权
    Folate conjugates 有权
    叶酸共轭物

    公开(公告)号：US08507455B2

    公开(公告)日：2013-08-13

    申请号：US12328537

    申请日：2008-12-04

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Muthusamy Jayaraman ,  Jayaprakash K. Narayanannair

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Muthusamy Jayaraman ,  Jayaprakash K. Narayanannair

    IPC分类号： C12N15/11 ,  A61K48/00 ,  C07H21/02 ,  C07H21/04

    CPC分类号： C12N15/113 ,  A61K47/55

    摘要： The present invention provides iRNA agent including at least one monomer having the structure shown in formula (I′) wherein: A and B are each independently for each occurrence O, N(RN) or S; X is H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a polymer, —P(Z′)(Z″)O-L6-Q′-L7-OP(Z′″)(Z′″″)O-oligonucleotide, a nucleotide, or an oligonucleotide; Y is H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z′)(Z″)O-L6-Q′-L7-OP(Z′″)(Z′″″)O-oligonucleotide, a nucleotide, or an oligonucleotide; R is folate, a folate analog a folate mimic or a folate receptor binding ligand; L6 and L7 are each independently for each occurrence —(CH2)n—, —C(R′)(R″)(CH2)n—, —(CH2)nC(R′)(R″)—, —(CH2CH2O)mCH2CH2—, or —(CH2CH2O)mCH2CH2NH—; Q′ is NH, O, S, CH2, C(O)O, C(O)NH, —NH—CH(Ra)—C(O)—, —C(O)—CH(Ra)—NH—, CO, where Ra is H or amino acid side chain; R′ and R″ are each independently H, CH3, OH, SH, NH2, NH(Alkyl=Me, Et, Pr, isoPr, Bu, Bn) or N(diAlkyl=Me2, Et2, Bn2); Z′, Z″, Z′″ and Z″″ are independently O or S; n represent independently for each occurrence 1-20; and m represent independently for each occurrence 0-50.

    摘要翻译： 本发明提供包含至少一种具有式（I'）所示结构的单体的iRNA试剂，其中：A和B各自独立地为O，N（RN）或S; X是H，保护基，磷酸基，磷酸二酯基，活化磷酸酯基，活化亚磷酸酯基，亚磷酰胺，固体载体，-P（Z'）（Z“）O-核苷，-P （Z'）（Z“）O-寡核苷酸，脂质，PEG，类固醇，聚合物，-P（Z'）（Z”）O-L6-Q'-L7-OP（Z“ '）（Z“”）O-寡核苷酸，核苷酸或寡核苷酸; Y是H，保护基，磷酸基，磷酸二酯基，活化磷酸酯基，活化亚磷酸酯基，亚磷酰胺，固体载体，-P（Z'）（Z“）O-核苷，-P （Z'）（Z“）（Z”）O-寡核苷酸，脂质，PEG，类固醇，亲脂性，聚合物，-P（Z'）（Z“）O-L6-Q'-L7-OP Z“'）（Z”“）O-寡核苷酸，核苷酸或寡核苷酸; R是叶酸，叶酸类似物叶酸类似物或叶酸受体结合配体; L 6和L 7各自独立地为 - （CH 2）n - ， - C（R'）（R“）（CH 2）n - ， - （CH 2）n C（R'）（R” （CH 2 CH 2 O）mCH 2 CH 2 - 或 - （CH 2 CH 2 O）m CH 2 CH 2 NH-; Q'是NH，O，S，CH2，C（O）O，C（O）NH，-NH-CH（Ra）-C（O） - ， - （O）-CH（Ra） ，CO，其中Ra为H或氨基酸侧链; R'和R“各自独立地为H，CH 3，OH，SH，NH 2，NH（烷基= Me，Et，Pr，isoPr，Bu，Bn）或N（二烷基= Me 2，Et 2，Bn 2）; Z'，Z“，Z”“和”Z“独立地为O或S; n每次出现1-20，独立地表示1-20; 而m代表每次出现的0-50。

    Oligonucleotides comprising a non-phosphate backbone linkage
    38.
    发明授权
    Oligonucleotides comprising a non-phosphate backbone linkage 有权
    包含非磷酸骨架键的寡核苷酸

    公开(公告)号：US07723512B2

    公开(公告)日：2010-05-25

    申请号：US12496250

    申请日：2009-07-01

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    IPC分类号： C07H19/00 ,  C07H19/22

    CPC分类号： C12N15/111 ,  C07H19/04 ,  C07H19/12 ,  C07H19/16 ,  C07H19/167 ,  C07H19/173 ,  C07H21/02 ,  C12N15/1136 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2320/51

    摘要： One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

    摘要翻译： 本发明的一个方面涉及在3'-位被亚磷酰胺基取代的核糖核苷。 在某些实施方案中，亚磷酰胺是烷基亚磷酰胺。 本发明的另一方面涉及包含至少一种非磷酸键的双链寡核苷酸。 代表性的非磷酸酯键包括膦酸酯，羟胺，羟基肼基，酰胺和氨基甲酸酯键。 在某些实施方案中，非磷酸酯键是膦酸酯键。 在某些实施方案中，非磷酸酯键仅出现在一条链中。 在某些实施方案中，在两条链中都发生非磷酸连接。 在某些实施方案中，配体与包含双链寡核苷酸的寡核苷酸链之一结合。 在某些实施方案中，配体与包含双链寡核苷酸的两条寡核苷酸链结合。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一种非磷酸键的单链寡核苷酸。 代表性的非磷酸酯键包括膦酸酯，羟胺，羟基肼基，酰胺和氨基甲酸酯键。 在某些实施方案中，非磷酸酯键是膦酸酯键。 在某些实施方案中，配体与寡核苷酸链结合。 在某些实施方案中，寡核苷酸包含至少一个修饰的糖部分。

    Oligonucleotides comprising a non-phosphate backbone linkage
    39.
    发明授权
    Oligonucleotides comprising a non-phosphate backbone linkage 有权
    包含非磷酸骨架键的寡核苷酸

    公开(公告)号：US07615618B2

    公开(公告)日：2009-11-10

    申请号：US11170798

    申请日：2005-06-29

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    IPC分类号： C07H19/00 ,  C07H21/00

    CPC分类号： C12N15/111 ,  C07H19/04 ,  C07H19/12 ,  C07H19/16 ,  C07H19/167 ,  C07H19/173 ,  C07H21/02 ,  C12N15/1136 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2320/51

    摘要： One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

    摘要翻译： 本发明的一个方面涉及在3'-位被亚磷酰胺基取代的核糖核苷。 在某些实施方案中，亚磷酰胺是烷基亚磷酰胺。 本发明的另一方面涉及包含至少一种非磷酸键的双链寡核苷酸。 代表性的非磷酸酯键包括膦酸酯，羟胺，羟基肼基，酰胺和氨基甲酸酯键。 在某些实施方案中，非磷酸酯键是膦酸酯键。 在某些实施方案中，非磷酸酯键仅出现在一条链中。 在某些实施方案中，在两条链中都发生非磷酸连接。 在某些实施方案中，配体与包含双链寡核苷酸的寡核苷酸链之一结合。 在某些实施方案中，配体与包含双链寡核苷酸的两条寡核苷酸链结合。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一种非磷酸键的单链寡核苷酸。 代表性的非磷酸酯键包括膦酸酯，羟胺，羟基肼基，酰胺和氨基甲酸酯键。 在某些实施方案中，非磷酸酯键是膦酸酯键。 在某些实施方案中，配体与寡核苷酸链结合。 在某些实施方案中，寡核苷酸包含至少一个修饰的糖部分。