Patent ID: 6028188
Filing Date: 2000-02-22
Classification: A61K,C07H

Abstract:
A method for making a synthetic Oligomer which hybridizes to an RNA target sequence, comprising the steps of:(a) identifying a single stranded RNA target sequence;(b) synthesizing a nucleoside dimer, trimer or tetramer having racemic internucleosidyl phosphonate linkages;(c) purify ing from said racemic nucleoside dimer, trimer or tetramer a chirally pure nucleoside dimer, trimer or tetramer; and(d) sequentially linking two or more of said chirally pure nucleoside dimers, trimers or tetramers to form a synthetic Oligomer having chirally pure phosphonate internucleosidyl linkages selected from the group consisting of lower alkyl- or arylphosphonate internucleosidyl linkages and lower alkyl- or arylphosphonothioate internucleosidyl linkages which are mixed with non-phosphonate internucleosidyl linkages wherein the chirally pure phosphonate linkages are interspersed between single non-phosphonate internucleosidyl linkages in a ratio of from 1 non-phosphonate linkage to about 1 phosphonate linkage to 1 non-phosphonate linkage to about 4 phosphonate linkages and wherein the Oligomer is substantially complementary to said identified RNA target sequence.