Complement factor b (cfb) irna compositions and methods of use thereof

A method of inhibiting expression of a complement factor B (CFB) gene in a cell, the method comprising contacting the cell with a dsRNA agent that inhibits the expression of CFB, 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, thereby inhibiting expression of the CFB gene in the cell.

A method of treating a subject having a disorder that would benefit from reduction in complement factor B expression, the method comprising administering to the subject a therapeutically effective amount of a dsRNA agent that inhibits the expression of CFB, 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, thereby treating the subject having the disorder that would benefit from reduction in complement factor B expression.

A double stranded ribonucleic acid (dsRNA) for inhibiting expression of complement factor B (CFB) in a cell, wherein the dsRNA comprises a sense strand and an antisense strand forming a double stranded region,

• (a) wherein the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense nucleotide sequences in any one of Tables 2-3;
• or
• (b) wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than three nucleotides from any one of the nucleotide sequence of nucleotides 504-526, 640-662, 641-663, 995-1017, 997-1019, 1034-1056, 1141-1163, 1145-1167, 1389-1411, 1473-1495, 1826-1848, 1828-1850, 1842-1864, 2242-2264, 2391-2413, 2393-2415, 2438-2460, or 2453-2475 of SEQ ID NO:
• 1, and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than three nucleotides from the corresponding nucleotide sequence of SEQ ID NO:8.