US 12,071,620 B2
Polynucleotides containing a morpholino linker
Gabor Butora, Cambridge, MA (US); Andrew W. Fraley, Arlington, MA (US); Edward John Miracco, Cambridge, MA (US); Jennifer Nelson, Brookline, MA (US); Amy Rhoden Smith, Watertown, MA (US); and Matthew Stanton, Marlton, NJ (US)
Assigned to ModernaTX, Inc., Cambridge, MA (US)
Filed by ModernaTX, Inc., Cambridge, MA (US)
Filed on Sep. 6, 2022, as Appl. No. 17/929,956.
Application 17/929,956 is a continuation of application No. 15/760,667, granted, now 11,434,486, issued on Sep. 6, 2022, previously published as PCT/US2016/052482, filed on Sep. 19, 2016.
Claims priority of provisional application 62/279,486, filed on Jan. 15, 2016.
Claims priority of provisional application 62/219,969, filed on Sep. 17, 2015.
Prior Publication US 2023/0323344 A1, Oct. 12, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/113 (2010.01); C12N 15/11 (2006.01)
CPC C12N 15/113 (2013.01) [C12N 15/111 (2013.01); C12N 2310/317 (2013.01); C12N 2310/321 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/3233 (2013.01); C12N 2310/351 (2013.01); C12N 2320/51 (2013.01)] 20 Claims
 
1. A compound, or a salt thereof, including:
a) a polynucleotide; and
b) at least one of a nucleotide, a second polynucleotide, targeting moiety, small molecule, polypeptide, or polymer,
wherein the polynucleotide of a) is conjugated to the nucleotide, second polynucleotide, targeting moiety, small molecule, polypeptide, or polymer via a linker including the structure of Formula I:

OG Complex Work Unit Chemistry
wherein B is a nucleobase, hydrogen, halo, hydroxy, thiol, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted amino, azido, optionally substituted C3-C10 cycloalkyl, optionally substituted C6-C10 aryl, or optionally substituted C2-C12 heterocycle;
X1 is O, S, NRU, or C(RU)2, wherein each RU is, independently, H, halo, or optionally substituted C1-C6 alkyl;
X2 is —O—, —NRN1—, —NRN1NRN1—, a bond, optionally substituted C1-C10 alkylene, optionally substituted C2-C10 alkenylene, optionally substituted C2-C10 alkynylene, optionally substituted C2-C10 heterocyclylene, optionally substituted C6-C12 arylene, optionally substituted C2-C100 polyethylene glycolene, or optionally substituted C1-C30 heteroalkylene, wherein RN1 is H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, or optionally substituted C6-C10 aryl;
m is 1, 2, 3, 4, or 5;
each L is, independently, an unbranched or branched linker;
R1 and R2 are each, independently, hydrogen, hydroxyl, or C1-C6 alkoxy, and
wherein if B is nucleobase, R1 and R2 are hydrogen and the linker conjugates the polynucleotide of a) to the second polynucleotide then X2-(L)m is not a furanylmethyl moiety, a pyranylmethyl moiety, —P(O)OH—, or —P(O)N(RN)2—, wherein RN is optionally substituted C1-C6 alkyl.