US 2026/0226466 A1 · METHODS AND COMPOSITIONS FOR TREATING CTNNB1-ASSOCIATED DISORDERS

Abstract

The present invention relates to methods and compostions comprising RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the beta-catenin (CTNNB1) gene for treating CTNNB1-associated disorders, such as cancer, e.g., hepatocellular carcinoma and colorectal cancer. The present invention also relates to combination therapies of RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the beta-catenin (CTNNB1) gene, and one or more treatments and/or therapeutic agents, e.g., immunotherapeutic agents, e.g., one or more immune checkpoint inhibitors, e.g., a PD-1 inhibitor, e.g., an anti-PD-1 antibody, or antigen-binding fragment thereof, a PD-L1 inhibitor, a CTLA-4 inhibitor, and/or VEGF inhibitors, for treating a subject having a CTNNB1-associated disorder, such as cancer, e.g., hepatocellular carcinoma and colorectal cancer.

Claims35

Dependent claims

A method of treating a subject having a cancer, the method comprising administering to the subject a dose of about 0.01 mg/kg to about 1.5 mg/kg of a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of beta-catenin (CTNNB1), or a salt thereof,

wherein the dsRNA agent, or a salt thereof, comprises a sense strand and an antisense strand,
wherein the sense strand differs by no more than 4 bases from the nucleotide sequence 5′-usascuguugGfAfUfugauucgasasa-3′ of SEQ ID NO:823 and the antisense strand differs by no more than 4 bases from the nucleotide sequence 5′-VPudTucdGadAucaadTcCfaacaguasgsc-3′ of SEQ ID NO:1164,
wherein a, g, c and u are 2′-O-methyl (2′-OMe) adenosine-, guanosine-, cytosine-, and uridine-3′-phosphate, respectively;
Af, Gf, Cf and Uf are 2′-fluoro adenosine-, guanosine-, cytosine-, and uridine-3′-phosphate, respectively;
s is a phosphorothioate linkage;
VP is a vinyl phosphonate;
dT is 2′-deoxythimidine-3′-phosphate;
dG is 2′-deoxyguanosine-3′-phosphate;
and dA is 2′-deoxyadenosine-3′-phosphate, thereby treating the subject having the cancer.

6 more elements

Dependencies are inferred from the claim text.

Methods and compositions for treating ctnnb1-associated disorders

Life of this patent

Methods and compositions for treating ctnnb1-associated disorders

Life of this patent

Abstract

Claims35