Folate conjugates
    5.
    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

    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。

    CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES
    6.
    发明申请
    CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES 有权
    碳氢化合物作为交付剂的交付代理

    公开(公告)号:US20120136042A1

    公开(公告)日:2012-05-31

    申请号:US13326203

    申请日:2011-12-14

    摘要: The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(RN) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl 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-Linker-OP(Z′″)(Z″″)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)— or -Linker-R; R is LG, -Linker-LG, or has the structure shown below: LG is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide; RN is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z′, Z″, Z′″ and Z″″ are each independently for each occurrence O or S.

    摘要翻译: 本发明提供包含至少一个式(I)亚基的iRNA试剂:其中:A和B各自独立地为O,N(RN)或S; X和Y各自独立地为H,OH,羟基保护基,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,亲脂性,聚合物,-P(Z')(Z“)O-Linker- OP(Z'“)(Z”“) - 寡核苷酸,寡核苷酸,-P(Z')(Z”) - 式(I),-P(Z')(Z“) - 链接器R R是LG,-Linker-LG,或具有如下结构:每次出现LG独立为碳水化合物,例如单糖,二糖,三糖,四糖,寡糖,多糖; 乙烯基,丙基,异丙基,丁基或苄基各自独立地为N, 和Z',Z“,Z”“和Z”“各自独立地为O或S.

    Carbohydrate conjugates as delivery agents for oligonucleotides
    10.
    发明授权
    Carbohydrate conjugates as delivery agents for oligonucleotides 有权
    碳水化合物缀合物作为寡核苷酸的递送剂

    公开(公告)号:US08106022B2

    公开(公告)日:2012-01-31

    申请号:US12328528

    申请日:2008-12-04

    IPC分类号: A01N43/04 A61K31/70

    摘要: The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(RN) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl 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-Linker-OP(Z′″)(Z″″)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)— or -Linker-R; R is LG, -Linker-LG, or has the structure shown below: LG is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide; RN is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z′, Z″, Z′″ and Z″″ are each independently for each occurrence O or S.

    摘要翻译: 本发明提供包含至少一个式(I)亚基的iRNA试剂:其中:A和B各自独立地为O,N(RN)或S; X和Y各自独立地为H,OH,羟基保护基,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,亲脂性,聚合物,-P(Z')(Z“)O-Linker- OP(Z'“)(Z”“) - 寡核苷酸,寡核苷酸,-P(Z')(Z”) - 式(I),-P(Z')(Z“) - 链接器R R是LG,-Linker-LG,或具有如下结构:每次出现LG独立为碳水化合物,例如单糖,二糖,三糖,四糖,寡糖,多糖; 乙烯基,丙基,异丙基,丁基或苄基各自独立地为N, 和Z',Z“,Z”“和Z”“各自独立地为O或S.