US 12,264,175 B2
Compositions and methods for capping RNAS
Christopher Cheng, North Reading, MA (US); Kallanthottathil Rajeev, Wayland, MA (US); and Caroline Reiss, Somerville, MA (US)
Assigned to Verve Therapeutics, Inc., Boston, MA (US)
Filed by Verve Therapeutics, Inc., Boston, MA (US)
Filed on Mar. 1, 2023, as Appl. No. 18/176,609.
Application 18/176,609 is a continuation of application No. PCT/US2021/049158, filed on Sep. 3, 2021.
Claims priority of provisional application 63/074,993, filed on Sep. 4, 2020.
Prior Publication US 2023/0331763 A1, Oct. 19, 2023
Int. Cl. C07H 21/02 (2006.01); C12N 9/12 (2006.01); C12P 19/34 (2006.01); A61K 31/7115 (2006.01); A61K 31/712 (2006.01); A61K 31/7125 (2006.01)
CPC C07H 21/02 (2013.01) [C12N 9/1247 (2013.01); C12P 19/34 (2013.01); C12Y 207/07006 (2013.01); A61K 31/7115 (2013.01); A61K 31/712 (2013.01); A61K 31/7125 (2013.01)] 6 Claims
OG exemplary drawing
 
1. An in vitro-transcribed (IVY) mRNA sequence initiator comprising a compound of formula (II) or a salt or solvate thereof:

OG Complex Work Unit Chemistry
Wherein
B1 is

OG Complex Work Unit Chemistry
each B2, B3, and Bn is independently a natural, a modified, or an unnatural nucleobase;
each Z′ and Z″ is independently is hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —NH(CH3), —NH3, —NH(C(═O)CH3), or —SCH3;
Z′″ is hydrogen, fluorine, —CH3, —CH2CH3, —OCH3, or —OCH2CH3;
each Z1 and Z2 is independently hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —SCH3, —OCH2CH3, —NH2, NHCH3, or NHC(═O)CH3;
each Z3, Z4, and Zn is independently hydrogen, fluorine, —OH, —CH3, —CH2CH3, —OCH3, —NH2, —NHCH3, —NH(C(═O)CH3), —OCH2CH3, —OCH2OCH3, —OCH2CH2CH3, —OCH(CH3)2, —SCH3, or —OCH2CH2OCH3;
each Q1 and Q4 is independently —CH═CH—, —CH2—, —CH2O—, —CH2S—, —CH2CH2—, —CH2CF2—, —CH2NH2—, —CH2NH(CH3)—, or —CH2N(C(═O)CH3);
each Q2 and Q3 is independently —O—, —S—, —CH2—, —CF2—, —NH—, —N(CH3)—, or —N(C(═O)CH3)—;
each X1, X2, X3, X4, and X5 is independently —OH, —SH, —O−, —S−, —NH2, —NHCH3, —NH(C(═O)CH3), —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2—OCH3 or —OCH2CH3;
each Y1, Y2, Y3, Y4, and Y5 is independently ═O, ═S, ═NH, or ═NCH3;
each A, A1, and A2 is independently —O—, —S—, —CH2—, —NH—, —N(CH3)— or —N(C(═O)CH3); and
p=0, 1, 2, 3, 4, 5 or 6.