Factor XII (Hageman Factor) (F12), KALLIKREIN B, PLASMA (FLETCHER FACTOR) 1 (KLKB1), and Kininogen 1 (KNG1) iRNA COMPOSITIONS AND METHODS OF USE THEREOF

1 . A double stranded ribonucleic acid (dsRNA) agent selected from the group consisting of

a) a dsRNA agent for inhibiting expression of Factor XII (Hageman Factor) (F12), wherein said dsRNA agent 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:9 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:10;

b) a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Factor XII (Hageman Factor) (F12), wherein said dsRNA agent 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 9, 10, 19C, 19D, 20, 21, 23, 24, 26, and 27;

c) a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Kallikrein B, Plasma (Fletcher Factor) 1 (KLKB1), wherein said dsRNA agent 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:2;

d) a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of a Kallikrein B, Plasma (Fletcher Factor) 1 (KLKB1), wherein said dsRNA agent 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, 19A, or 19B;

e) a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Kininogen 1 (KNG1), wherein said dsRNA agent 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:17 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:18; and

f)_a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of a Kininogen 1 (KNG1), wherein said dsRNA agent 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 15, 16, 19E or 19F;

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

2 . (canceled)

3 . The dsRNA agent of claim 1 , wherein all of the nucleotides of said sense strand and all of the nucleotides of said antisense strand comprise a modification.

4 . The dsRNA agent of claim 1 , wherein the at least one modified nucleotide is selected from the group consisting of a deoxy-nucleotide, a 3′-terminal deoxy-thymine (dT) nucleotide, a 2′-O-methyl modified nucleotide, a 2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an unlocked nucleotide, a conformationally restricted nucleotide, a constrained ethyl nucleotide, an abasic nucleotide, a 2′-amino-modified nucleotide, a 2′-O-allyl-modified nucleotide, 2′-C-alkyl-modified nucleotide, 2′-hydroxly-modified nucleotide, a 2′-methoxyethyl modified nucleotide, a 2′-O-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a tetrahydropyran modified nucleotide, a 1,5-anhydrohexitol modified nucleotide, a cyclohexenyl modified nucleotide, a nucleotide comprising a phosphorothioate group, a nucleotide comprising a methylphosphonate group, a nucleotide comprising a 5′-phosphate, and a nucleotide comprising a 5′-phosphate mimic.

5 . The dsRNA agent of claim 1 , further comprising at least one phosphorothioate internucleotide linkage.

6 . The dsRNA agent of claim 1 , wherein the region of complementarity is 19 to 30 nucleotides in length; 21 to 23 nucleotides in length; 21 nucleotides in length; 19 nucleotides in length; or at least 17 nucleotides in length.

7 . The dsRNA agent of claim 1 , wherein each strand is no more than 30 nucleotides in length; each strand is independently 19-30 nucleotides in length; or each strand is independently 19-25 nucleotides in length.

8 . The dsRNA agent of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide; or a 3′ overhang of at least 2 nucleotides.

9 . The dsRNA agent of claim 31 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent.

10 . The dsRNA agent of claim 9 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

11 . The dsRNA agent of claim 10 , wherein the ligand is

12 . The dsRNA agent of claim 11 , wherein the dsRNA agent is conjugated to the ligand as shown in the following schematic

and, wherein X is O or S.

13 . (canceled)

14 . (canceled)

15 . A pharmaceutical composition for inhibiting expression of a KLKB1 gene, an F12 gene, or a KNG gene, comprising the dsRNA agent of claim 1 .

16 . (canceled)

17 . (canceled)

18 . A method of inhibiting expression of a KLKB1 gene, an F12 gene, or a KNG gene in a cell, the method comprising:

(a) contacting the cell with the dsRNA agent of claim 1 , or a pharmaceutical composition of claim 15 ; and

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

19 . The method of claim 18 , wherein said cell is within a subject.

20 . The method of claim 19 , wherein the subject is a human.

21 . A method of treating a subject having a disease or disorder that would benefit from reduction in expression of a contact activation pathway gene, the method comprising administering to the subject a therapeutically effective amount of the dsRNA agent of claim 1 , or a pharmaceutical composition of claim 15 , thereby treating said subject.

22 .- 30 . (canceled)

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