US 11,725,208 B2
Conjugated antisense compounds and their use
Michael Oestergaard, Carlsbad, CA (US); Punit P. Seth, Carlsbad, CA (US); Frank Rigo, Carlsbad, CA (US); and Chrissa A. Dwyer, San Diego, CA (US)
Assigned to Ionis Pharmaceuticals, Inc., Carlsbad, CA (US)
Appl. No. 16/771,620
Filed by Ionis Pharmaceuticals, Inc., Carlsbad, CA (US)
PCT Filed Dec. 14, 2018, PCT No. PCT/US2018/065830
§ 371(c)(1), (2) Date Jun. 10, 2020,
PCT Pub. No. WO2019/118916, PCT Pub. Date Jun. 20, 2019.
Claims priority of provisional application 62/598,926, filed on Dec. 14, 2017.
Prior Publication US 2020/0392509 A1, Dec. 17, 2020
Int. Cl. C12N 15/113 (2010.01); A61K 9/00 (2006.01)
CPC C12N 15/1137 (2013.01) [A61K 9/0085 (2013.01); C12N 15/113 (2013.01); C12N 2310/11 (2013.01); C12N 2310/113 (2013.01); C12N 2310/31 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/3341 (2013.01); C12N 2310/351 (2013.01); C12N 2310/3515 (2013.01); C12N 2310/3535 (2013.01); C12N 2320/32 (2013.01)] 33 Claims
 
1. A compound comprising a first oligomeric compound and a second oligomeric compound, wherein the first oligomeric compound comprises a first modified oligonucleotide consisting of 14-20 linked nucleosides and has a nucleobase sequence complementary to the nucleobase sequence of the second oligomeric compound and to a nucleic acid target; and
the second oligomeric compound comprises a second modified oligonucleotide consisting of 6-12 linked nucleosides;
wherein the first modified oligonucleotide has a sugar motif comprising:
a 5′-region consisting of 1-5 linked 5′-nucleosides,
a central region consisting of 6-10 linked central region nucleosides, and
a 3′-region consisting of 1-5 linked 3′-nucleosides; wherein
each of the 5′-region nucleosides and each of the 3′-region comprises a modified sugar moiety and each of the central region nucleosides comprises an unmodified DNA sugar moiety; and
wherein the second modified oligonucleotide has a sugar motif comprising:
a 5′-region consisting of 2-4 linked 5′-nucleosides,
a central region consisting of 2-4 linked central region nucleosides, and
a 3′-region consisting of 2-4 linked 3′-nucleosides; wherein
each of the 5′-region nucleosides and each of the 3′-region comprises a modified sugar moiety and each of the central region nucleosides comprises an unmodified DNA sugar moiety.