US 12,241,065 B2
Antisense oligonucleotides targeting alpha-synuclein and uses thereof
Richard E. Olson, Cambridge, MA (US); Angela M. Cacace, Haddam Neck, CT (US); Jere E. Meredith, Jr., Haddam, CT (US); Nino Devidze, Conshohocken, PA (US); James K. Loy, Gales Ferry, CT (US); Carl J. Baldick, Pennington, NJ (US); Annapurna Pendri, South Glastonbury, CT (US); Ivar M. McDonald, Woodstock, CT (US); Peter Hagedorn, Hørsholm (DK); and Marianne Lerbech Jensen, Køge (DK)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US); and Roche Innovation Center Copenhagen A/S, Hørsholm (DK)
Appl. No. 16/961,578
Filed by Bristol-Myers Squibb Company, Princeton, NJ (US); and Roche Innovation Center Copenhagen A/S, Hørsholm (DK)
PCT Filed Jan. 11, 2019, PCT No. PCT/US2019/013255
§ 371(c)(1), (2) Date Jul. 10, 2020,
PCT Pub. No. WO2019/140236, PCT Pub. Date Jul. 18, 2019.
Claims priority of provisional application 62/616,994, filed on Jan. 12, 2018.
Prior Publication US 2020/0362347 A1, Nov. 19, 2020
Int. Cl. C12N 15/113 (2010.01); A61K 9/00 (2006.01); A61K 31/7088 (2006.01); A61K 39/395 (2006.01)
CPC C12N 15/113 (2013.01) [A61K 9/0085 (2013.01); A61K 31/7088 (2013.01); A61K 39/3955 (2013.01); C12N 2310/31 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/3341 (2013.01); C12N 2310/341 (2013.01); C12N 2310/351 (2013.01); C12N 2320/31 (2013.01); C12N 2320/32 (2013.01)] 11 Claims
 
1. An antisense oligonucleotide comprising a contiguous nucleotide sequence of 10 to 30 nucleotides in length that are complementary to a nucleic acid sequence within an alpha-synuclein (SNCA) transcript, wherein the contiguous nucleotide sequence comprises a sequence as set forth in:
(i) SEQ ID NO: 7 with the design of AttCctttacaccACaCT (ASO-005578), AttCctttacaccAcACT (ASO-005584), AttCctttacaccaCACT (ASO-005597), or AttCctttacaccacACT (ASO-005611);
(ii) SEQ ID NO: 9 with the design of AatTCctttacaccacACT (ASO-005717) or AAttCctttacaccaCACT (ASO-005700);
(iii) SEQ ID NO: 12 with the design of ttccTttacaccacac (ASO-288906), ttCctttacaccAcAc (ASO-287957), TtcctttacaccaCaC (ASO-287959), or ttCctttacaccACac (ASO-287962); or
(iv) SEQ ID NO: 14 with the design of AAttcctttacACCAcAC (ASO-005650), AAttCctttacacCaCAC (ASO-005496), or AAttCCtTtacaccacAC (ASO-005392);
wherein the upper case letter is a beta-D-oxy-locked nucleic acid (LNA) and the lower case letter is a DNA.