发明申请
- 专利标题: Folate Conjugates
- 专利标题(中): 叶酸缀合物
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申请号: US12328537申请日: 2008-12-04
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公开(公告)号: US20090247614A1公开(公告)日: 2009-10-01
- 发明人: Muthiah Manoharan , Kallanthottathil G. Rajeev , Muthusamy Jayaraman , Jayaprakash K. Narayanannair
- 申请人: Muthiah Manoharan , Kallanthottathil G. Rajeev , Muthusamy Jayaraman , Jayaprakash K. Narayanannair
- 申请人地址: US MA Cambridge
- 专利权人: ALNYLAM PHARMACEUTICALS, INC.
- 当前专利权人: ALNYLAM PHARMACEUTICALS, INC.
- 当前专利权人地址: US MA Cambridge
- 主分类号: A61K31/7088
- IPC分类号: A61K31/7088 ; C07H21/02 ; C12N5/02
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 L1 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.
公开/授权文献
- US08507455B2 Folate conjugates 公开/授权日:2013-08-13
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