Complement component C5 iRNA compositions and methods of use thereof

A double stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of complement component C5 in a cell, wherein said dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region, wherein said antisense strand comprises a region of complementarity which comprises at least 17 contiguous nucleotides differing by no more than 3 nucleotides from nucleotides 780-802 of SEQ ID NO:1, wherein each strand is independently about 14 to about 30 nucleotides in length, wherein said dsRNA agent is represented by formula (III):

• (III)
• sense:
• 5′ np-Na-(X X X)i-Nb-Y Y Y-Nb-(Z Z Z)j-Na-nq 3′
• antisense:
• 3′ np′-Na′-(X′X′X′)k-Nb′-Y′Y′Y′-Nb′-(Z′Z′Z′)l-Na′-
• nq′ 5′
• wherein:
• i, j, k, and l are each independently 0 or 1;
• p, p′, q, and q′ are each independently 0-6;
• each Na and Na′ independently represents an oligonucleotide sequence comprising 0-25 nucleotides which are modified, each sequence comprising at least two differently modified nucleotides;
• each Nb and Nb′ independently represents an oligonucleotide sequence comprising 0-10 nucleotides which are modified;
• each np, np′, nq, and nq′, each of which may or may not be present, independently represents an overhang nucleotide;
• XXX, YYY, ZZZ, X′X′X′, Y′Y′Y′, and Z′Z′Z′ each independently represent one motif of three identical modifications on three consecutive nucleotides;
• modifications on Nb differ from the modification on Y and modifications on Nb′ differ from the modification on Y′;
• and
• wherein the sense strand is conjugated to at least one ligand.

A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C5,

• wherein said dsRNA agent comprises a sense strand and an antisense strand each independently 15-30 nucleotides in length forming a double stranded region, the antisense strand comprising a region of complementarity comprising at least 17 contiguous nucleotides differing by no more than 3 nucleotides from nucleotides 780-802 of SEQ ID NO:1,
• wherein substantially all of the nucleotides of said sense strand and substantially all of the nucleotides of said antisense strand are modified nucleotides and the modifications are independently selected from the group consisting of a 2′-O-methyl modification and a 2′-fluoro modification,
• wherein said sense strand comprises two phosphorothioate internucleotide linkage at the 5′-terminus, and the antisense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus and two phosphorothioate internucleotide linkages at the 3′-terminus, and
• wherein said sense strand is conjugated to one or more GalNAc derivatives attached through a branched bivalent or trivalent linker at the 3′-terminus.