METHODS AND COMPOSITIONS FOR TREATING A PROPROTEIN CONVERTASE SUBTILISIN KEXIN (PCSK9) GENE-ASSOCIATED DISORDER

1 . A method of inhibiting the expression of a PCSK9 gene in a human subject, comprising administering to the subject a fixed dose of about 25 mg to about 800 mg of a double-stranded ribonucleic acid (RNAi) agent,

wherein the double-stranded RNAi agent comprises a sense strand and an antisense strand forming a double stranded region, the antisense strand comprising a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from nucleotides 3544-3623 of the nucleotide sequence of SEQ ID NO:1, thereby inhibiting the expression of the PCSK9 gene in the subject.

2 . A method of decreasing the level of low density lipoprotein cholesterol (LDLc) in serum in a human subject, comprising administering to the subject a fixed dose of about 25 mg to about 800 mg of a double-stranded ribonucleic acid (RNAi) agent,

wherein the double-stranded RNAi agent comprises a sense strand and an antisense strand forming a double stranded region, the antisense strand comprising a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from nucleotides 3544-3623 of the nucleotide sequence of SEQ ID NO:1, thereby decreasing the level of LDLc in the subject.

3 . (canceled)

4 . (canceled)

5 . The method of claim 1 , wherein the fixed dose is administered to the subject at an interval of once a week; once every two weeks; once a month; once a quarter; or bianually.

6 .- 9 . (canceled)

10 . The method of claim 5 , wherein the subject is administered a fixed dose of about 25 mg to about 50 mg once a week; a fixed dose of about 50 mg to about 100 mg once every two weeks; a fixed dose of about 100 mg to about 200 mg once a month; a fixed dose of about 200 mg to about 800 mg once a quarter; or a fixed dose of about 200 mg to about 800 mg biannually.

11 .- 18 . (canceled)

19 . The method of claim 1 , wherein the double stranded RNAi agent is administered to the subject subcutaneously.

20 . The method of claim 19 , wherein the subcutaneous administration is subcutaneous injection.

21 . (canceled)

22 . The method of claim 1 , wherein the antisense strand comprises a nucleotide sequence corresponding to the unmodified sequence of any one of the nucleotide sequences provided in Table 1.

23 . The method of claim 1 , wherein the antisense strand comprises the nucleotide sequence 5′-ACAAAAGCAAAACAGGUCUAGAA-3′(SEQ ID NO: 685).

24 . The method of claim 1 , wherein the sense strand comprises the nucleotide sequence 5′-CUAGACCUGUTUUGCUUUUGU-3′ (SEQ ID NO: 686).

25 .- 27 . (canceled)

28 . The method of claim 1 , wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification.

29 .- 62 . (canceled)

63 . The method of claim 1 , wherein the double-stranded ribonucleic acid RNAi agent further comprises a ligand.

64 . The method of claim 63 , wherein the ligand is conjugated to the 3′ end of the sense strand of the double-stranded ribonucleic acid RNAi agent.

65 . The method of claim 63 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

66 . The method of claim 65 , wherein the ligand is

67 . The method of claim 65 , wherein the double-stranded ribonucleic acid RNAi agent is conjugated to the ligand as shown in the following schematic

and, wherein X is O or S.

68 . The method of claim 67 , wherein the X is O.

69 .- 72 . (canceled)

73 . The method of claim 1 , further comprising administering an additional therapeutic agent to the subject.

74 .- 76 . (canceled)

77 . The method of claim 1 , wherein the RNAi agent is administered as a pharmaceutical composition.

78 .- 82 . (canceled)

83 . A kit for performing the method of claim 1 , comprising

a) the double-stranded RNAi agent, and

b) instructions for use, and

c) optionally, means for administering the double-stranded RNAi agent to the subject.