Complement factor B (CFB) iRNA compositions and methods of use thereof

1. 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.

2. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 1 , wherein the sense strand comprises a nucleotide sequence which differs by no more than 3 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 3 nucleotides from the nucleotide sequence 5′-asdGsucdAudAaaaudTcAfggaauucscsu-3′ of SEQ ID NO:1922.

3. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 1 , wherein the sense strand comprises a nucleotide sequence which differs by no more than 2 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 2 nucleotides from the nucleotide sequence 5′-asdGsucdAudAaaaudTcAfggaauucscsu-3′ of SEQ ID NO:1922.

4. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 1 , wherein the sense strand comprises a nucleotide sequence which differs by no more than 1 nucleotide 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 1 nucleotide from the nucleotide sequence 5′-asdGsucdAudAaaaudTcAfggaauucscsu-3′ of SEQ ID NO:1922.

5. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 1 , 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.

6. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 1 , 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.

7. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of any one of claims 1 - 6 , further comprising a ligand.

8. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 7 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent or a pharmaceutically acceptable salt thereof.

9. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 7 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

10. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 9 , wherein the ligand is conjugated to the dsRNA agent, or a pharmaceutically acceptable salt thereof, through a monovalent, bivalent, or trivalent linker.

11. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 9 , wherein the ligand is

12. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 11 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is conjugated to the ligand as shown in the following schematic

wherein X is O or S.

13. The dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 12 , wherein X is O.

14. An isolated cell containing the dsRNA agent, or a pharmaceutically acceptable salt thereof, of any one of claims 1 - 6 .

15. A pharmaceutical composition comprising the dsRNA agent, or a pharmaceutically acceptable salt thereof, of any one of claims 1 - 6 .

16. The pharmaceutical composition of claim 15 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is in an unbuffered solution.

17. The pharmaceutical composition of claim 16 , wherein the unbuffered solution is saline or water.

18. The pharmaceutical composition of claim 15 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is in a buffer solution.

19. The pharmaceutical composition of claim 18 , wherein the buffer solution comprises acetate, citrate, prolamine, carbonate, or phosphate or any combination thereof.

20. The pharmaceutical composition of claim 19 , wherein the buffer solution is phosphate buffered saline (PBS).

21. 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.

22. An isolated cell containing the dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 21 .

23. A pharmaceutical composition comprising the dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 21 .

24. The pharmaceutical composition of claim 23 , wherein dsRNA agent, or a pharmaceutically acceptable salt thereof, is in an unbuffered solution.

25. The pharmaceutical composition of claim 23 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is in a buffer solution.

26. 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.

27. An isolated cell containing the dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 26 .

28. A pharmaceutical composition comprising the dsRNA agent, or a pharmaceutically acceptable salt thereof, of claim 26 .

29. The pharmaceutical composition of claim 28 , wherein dsRNA agent, or a pharmaceutically acceptable salt thereof, is in an unbuffered solution.

30. The pharmaceutical composition of claim 28 , wherein said dsRNA agent, or a pharmaceutically acceptable salt thereof, is in a buffer solution.