US 11,926,832 B2
Ketohexokinase (KHK) iRNA compositions and methods of use thereof
Leila Noetzli, Boston, MA (US); James D. McIninch, Burlington, MA (US); Frederic Tremblay, Boston, MA (US); Mark K. Schlegel, Boston, MA (US); and Adam Castoreno, Framingham, MA (US)
Assigned to Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed on Dec. 2, 2022, as Appl. No. 18/060,990.
Application 18/060,990 is a continuation of application No. PCT/US2022/016890, filed on Feb. 18, 2022.
Claims priority of provisional application 63/280,668, filed on Nov. 18, 2021.
Claims priority of provisional application 63/223,581, filed on Jul. 20, 2021.
Claims priority of provisional application 63/154,005, filed on Feb. 26, 2021.
Prior Publication US 2023/0323363 A1, Oct. 12, 2023
Int. Cl. A61K 48/00 (2006.01); A61K 47/02 (2006.01); A61K 47/54 (2017.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01)
CPC C12N 15/1137 (2013.01) [A61K 47/02 (2013.01); A61K 47/549 (2017.08); C12N 2310/14 (2013.01); C12N 2310/314 (2013.01); C12N 2310/351 (2013.01); C12N 2310/53 (2013.01)] 30 Claims
OG exemplary drawing
 
1. A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of ketohexokinase (KHK) in a cell, or a pharmaceutically acceptable salt thereof, comprising a sense strand and an antisense strand forming a double stranded region,
wherein the nucleotide sequence of the sense strand differs by no more than 4 bases from the nucleotide sequence 5′-gscsaggaagCfAfCfugagauucgu-3′ (SEQ ID NO: 1420) and the nucleotide sequence of the antisense strand differs by no more than 4 bases from the nucleotide sequence 5′-asdCsgadAudCucagdTgCfuuccugcsasc-3′ (SEQ ID NO:1532),
wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively; Cf and Af are 2′-fluoro (2′-F) C and A, respectively; dC, dA, and dT are 2′-deoxy C, A, and T, respectively; and s is a phosphorothioate linkage, and
wherein the sense strand of the dsRNA agent is conjugated to a ligand.