Folate conjugates

US8507455B2 · kind B2 · utility

Assignee

• Alnylam Pharmaceuticals, Inc. · US

Inventors

• Muthiah Manoharan · Carlsbad, US
• Kallanthottathil G. Rajeev · Wayland, US
• Muthusamy Jayaraman · Cambridge, US
• Jayaprakash K. Narayanannair · Cambridge, US

Key dates

• Filing date: Dec 4, 2008
• Grant date: Aug 13, 2013
• Expiry date: Feb 1, 2032

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K47/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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…