US 12,404,508 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 Oct. 16, 2023, as Appl. No. 18/487,302.
Application 18/487,302 is a continuation of application No. 18/060,990, filed on Dec. 2, 2022, granted, now 11,926,832.
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 2024/0150769 A1, May 9, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 48/00 (2006.01); A61K 47/02 (2006.01); A61K 47/54 (2017.01); 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)] 29 Claims
OG exemplary drawing
 
1. A method of inhibiting expression of a ketohexokinase (KHK) gene in a cell, the method comprising contacting the cell with a double stranded ribonucleic acid (dsRNA) agent that inhibits expression of ketohexokinase (KHK), or a pharmaceutically acceptable salt thereof,
wherein the dsRNA agent comprises 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′ of 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′ of 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, thereby inhibiting expression of the KHK gene in the cell.