COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

1 . A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C5, wherein said dsRNA comprises a sense strand and an antisense strand, wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:1 and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:5.

2 . A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C5, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense sequences listed in any one of Tables 3, 4, 5, 6, 18, 19, 20, 21, and 23.

3 . The dsRNA agent of claim 1 , wherein said dsRNA agent comprises at least one modified nucleotide.

4 . 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 forming a double-stranded region,

wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:1 and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:5,

wherein substantially all of the nucleotides of said sense strand and substantially all of the nucleotides of said antisense strand are modified nucleotides, and

wherein said sense strand is conjugated to a ligand attached at the 3′-terminus.

5 . The dsRNA agent of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.

6 . The dsRNA agent of claim 1 , further comprising a ligand.

7 . 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 complementary to an antisense strand, wherein said antisense strand comprises a region complementary to part of an mRNA encoding C5, wherein each strand is about 14 to about 30 nucleotides in length, wherein said double stranded RNAi agent is represented by formula (III):

(III)

sense:

5′ n p -N a -(X X X) i -N b -Y Y Y-N b -(Z Z Z) j -N a -n q  3′

antisense:

3′ n p ′-N a ′-(X′X′X′) k -N b ′-Y′Y′Y′-N b ′-(Z′Z′Z′) l -N a ′-

n q ' 5′

wherein:

i, j, k, and l are each independently 0 or 1;

p, p′, q, and q′ are each independently 0-6;

each N a and N a ′ independently represents an oligonucleotide sequence comprising 0-25 nucleotides which are either modified or unmodified or combinations thereof, each sequence comprising at least two differently modified nucleotides;

each N b and N b ′ independently represents an oligonucleotide sequence comprising 0-10 nucleotides which are either modified or unmodified or combinations thereof;

each n p , n p ′, n q , and n q ′, 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 N b differ from the modification on Y and modifications on N b ′ differ from the modification on Y′; and

wherein the sense strand is conjugated to at least one ligand.

8 . The dsRNA agent of claim 1 , wherein the double-stranded region is 15-30 nucleotide pairs in length.

9 . The dsRNA agent of claim 7 , wherein the modifications on the nucleotides are 2′-O-methyl or 2′-fluoro modifications.

10 . The dsRNA agent of claim 7 , wherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker.

11 . The dsRNA agent of claim 1 , wherein said agent further comprises at least one phosphorothioate or methylphosphonate internucleotide linkage.

12 . The dsRNA agent of claim 1 , wherein the sense and antisense strands comprise sequences selected from the group consisting of any of the sequences in any one of Tables 3, 4, 5, 6, 18, 19, 20 21, and 23.

13 . A cell containing the dsRNA agent of claim 1 .

14 . A pharmaceutical composition for inhibiting expression of a complement component C5 gene comprising the dsRNA agent of claim 1 .

15 . A method of inhibiting complement component C5 expression in a cell, the method comprising:

(a) contacting the cell with the dsRNA agent of claim 1 or a pharmaceutical composition of claim 14 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a complement component C5 gene, thereby inhibiting expression of the complement component C5 gene in the cell.

16 . The method of claim 15 , wherein said cell is within a subject.

17 . The method of claim 16 , wherein the subject is a human.

18 . A method of treating a subject having a disease or disorder that would benefit from reduction in complement component C5 expression, the method comprising administering to the subject a therapeutically effective amount of the dsRNA agent of claim 1 or a pharmaceutical composition of claim 14 , thereby treating said subject.

19 . A method of preventing at least one symptom in a subject having a disease or disorder that would benefit from reduction in complement component C5 expression, the method comprising administering to the subject a prophylactically effective amount of the dsRNA agent of claim 1 or a pharmaceutical composition of claim 14 , thereby preventing at least one symptom in the subject having a disorder that would benefit from reduction in C5 expression.

20 . The method of claim 18 or 19 , wherein the disorder is a complement component C5-associated disease.