Complement factor B (CFB) iRNA compositions and methods of use thereof
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsJames D. McIninch, Mark K. Schlegel, Adam Castoreno, Elane Fishilevich, Kristina Yucius
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Abstract
The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the complement factor B (CFB) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a CFB gene and to methods of treating or preventing a CFB-associated disease in a subject.
Claims30
A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement factor B (CFB) in a cell, or a pharmaceutically acceptable salt thereof,
- wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises a nucleotide sequence which differs by no more than 4 nucleotides from the nucleotide sequence 5′-gsasauuccuGfAfAfuuuuaugacu-3′ of SEQ ID NO:1271 and the antisense strand comprises a nucleotide sequence which differs by no more than 4 nucleotides from the nucleotide sequence 5′-asdGsucdAudAaaaudTcAfggaauucscsu-3′ of SEQ ID NO:1922,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- Af and Gf, are 2′-fluoro A and G, respectively;
- dG is a 2′-deoxyguanosine-3′-phosphate nucleotide;
- dA is a 2′-deoxyadenosine-3′-phosphate nucleotide;
- dT is a 2′-deoxythymidine-3′-phosphate nucleotide;
- and s is a phosphorothioate linkage.
A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement factor B (CFB) in a cell, or a pharmaceutically acceptable salt thereof,
- wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises the nucleotide sequence 5′-gsasauuccuGfAfAfuuuuaugacu-3′ of SEQ ID NO:1271 and the antisense strand comprises the nucleotide sequence 5′-asdGsucdAudAaaaudTcAfggaauucscsu-3′ of SEQ ID NO:1922,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- Af and Gf are 2′-fluoro A and G, respectively;
- dG is a 2′-deoxyguanosine-3′-phosphate nucleotide;
- dA is a 2′-deoxyadenosine-3′-phosphate nucleotide;
- dT is a 2′-deoxythymidine-3′-phosphate nucleotide;
- and s is a phosphorothioate linkage, and
- wherein the 3′-end of the sense strand is conjugated to a ligand as shown in the following schematic
- wherein X is O.
A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement factor B (CFB) in a cell, or a pharmaceutically acceptable salt thereof,
- wherein the dsRNA, or a pharmaceutically acceptable salt thereof, comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand consists of the nucleotide sequence 5′-gsasauuccuGfAfAfuuuuaugacu-3′ of SEQ ID NO:1271 and the antisense strand consists of the nucleotide sequence 5′-asdGsucdAudAaaaudTcAfggaauucscsu-3′ of SEQ ID NO:1922,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- Af and Gf are 2′-fluoro A and G, respectively;
- dG is a 2′-deoxyguanosine-3′-phosphate nucleotide;
- dA is a 2′-deoxyadenosine-3′-phosphate nucleotide;
- dT is a 2′-deoxythymidine-3′-phosphate nucleotide;
- and s is a phosphorothioate linkage, and
- wherein the 3′-end of the sense strand is conjugated to a ligand as shown in the following schematic
- wherein X is O.
Dependencies are inferred from the claim text.