Patent ID: 9657296
Date: 2017-05-23
CPC Classifications: A61K,A61P,C07C,C07H,C12N,C12Y

Claim:
1. A method of synthesizing a lipid conjugated oligonucleotide comprising at least 5 contiguous nucleoside subunits complementary to the RNA component of human telomerase each subunit joined by a N3′→P5′ thiophosphoramidate linkage, the method comprising: (a) deprotecting and reacting a lipid containing solid support with a first 3′-protected aminonucleoside-5′-O-cyanoethyl-N,N-diisopropylaminophosphoramidite monomer to produce a first nucleoside attached to the lipid containing solid support through a phosphite linkage, wherein after the deprotecting the lipid containing solid support comprises the structure wherein Suc is a succinyl group that is attached to the solid support and R″ is the carbon chain of a fatty acid lipid or a sterol; (b) sulfurizing the phosphite linkage to form a thiophosphate linkage; (c) deprotecting the protected 3′-amino group of the first aminonucleoside to form a free 3′-amino group; (d) reacting the free 3′-amino group with a second 3′-protected aminonucleoside-5′-O-cyanoethyl-N,N-diisopropylaminophosphoramidite monomer to form an internucleoside N3′→P5′ phosphoramidite linkage; and (e) sulfurizing the internucleoside N3′→P5′ phosphoramidite linkage to form a N3′→P5′ thiophosphoramidate linkage; and (f) repeating steps (c) through (e) to produce the lipid conjugated oligonucleotide.