Antisense nucleic acid targeting APOC3

1 . An antisense oligomer, pharmaceutically acceptable salt thereof or pharmaceutically acceptable hydrate thereof consisting of any of the following base sequences:

(SEQ ID NO: 26)

AGAatactgtcCCt 

(SEQ ID NO: 37)

TgAg A atactgtcCCt 

(SEQ ID NO: 38)

GAg A atactgtcCCt 

(SEQ ID NO: 39)

AG A atactgtccCTt 

(SEQ ID NO: 40)

TgAg A atactgtccCTt 

(SEQ ID NO: 41)

AcTgag A atactgtcccTtT 

(SEQ ID NO: 38)

GAG R A atactgtcCCt 

(SEQ ID NO: 38)

GAG F A atactgtcCCt 

(SEQ ID NO: 38)

GA GA atactgtcCCt 

(SEQ ID NO: 38)

GAG F A R atactgtcCCt 

(SEQ ID NO: 38)

GA R G A atactgtcCCt 

(SEQ ID NO: 38)

GA F G A atactgtcCCt 

(SEQ ID NO: 38)

G A G A atactgtcCCt 

wherein

upper-case letters indicate LNA (Locked Nucleic Acid) (C is 5-methylcytosine LNA),

lower case letters indicate DNA,

upper case letters+underline indicates 2′-O-Me modification,

N R indicates RNA (2′-OH) (“N” indicates any base),

N F indicates 2′-Fluoro modification, and

each internucleoside bond indicates phosphorothioate bond.

2 . An oligonucleotide conjugate wherein a molecule capable of binding to an asialoglycoprotein receptor is added to one or both ends of the oligonucleotide strand of the antisense oligomer, pharmaceutically acceptable salt thereof or pharmaceutically acceptable hydrate thereof according to claim 1 , wherein the molecule capable of binding to an asialoglycoprotein receptor is selected from the group consisting of lactose, galactose, N-acetylgalactosamine (GalNAc), galactosamine, N-formylgalactosamine, N-propionylgalactosamine, N-n-butanoylgalactosamine, and N-iso-butanoylgalactosamine.

3 . The oligonucleotide conjugate according to claim 2 , wherein

the end of the oligonucleotide strand and the molecule capable of binding to an asialoglycoprotein receptor are bound via a linker,

the linker comprises a main chain linker that binds to the end of the oligonucleotide strand, and a side chain linker that branches from the main chain and binds to the molecule capable of binding to an asialoglycoprotein receptor,

the main chain linker is a straight chain carbon chain selected from the group consisting of ethylene chain, propylene chain, butylene chain, pentylene chain, hexylene chain, heptylene chain, octylene chain, nonylene chain, decylene chain, dodecylene chain, tetradecylene chain, hexadecylene chain, and octadecylene chain (provided that when the side chain linker comprises a hetero atom, it optionally forms a heterocyclic ring together with a carbon atom of the main chain), and

wherein the end of the oligonucleotide and the main chain linker, and, when two or more molecules capable of binding to asialoglycoprotein receptors are added, further the main chain linkers, are linked by phosphodiester bonds.

4 . A pharmaceutical composition for inhibiting APOC3 protein expression, comprising the antisense oligomer, pharmaceutically acceptable salt thereof or pharmaceutically acceptable hydrate thereof according to claim 1 .

5 . A method for treating hypertriglyceridemia in a subject, comprising administering to the subject an effective amount of the antisense oligomer, pharmaceutically acceptable salt thereof or pharmaceutically acceptable hydrate thereof according to claim 1 .

6 . A method for treating primary hyperchylomicronemia in a subject, comprising administering to the subject an effective amount of the antisense oligomer, pharmaceutically acceptable salt thereof or pharmaceutically acceptable hydrate thereof according to claim 1 .

7 . A method for inhibiting APOC3 protein expression in a subject, comprising administering to the subject an effective amount of the oligonucleotide conjugate according to claim 2 .

8 . A method for treating hypertriglyceridemia in a subject, comprising administering to the subject an effective amount of the oligonucleotide conjugate according to claim 2 .

9 . A method for treating for primary hyperchylomicronemia in a subject, comprising administering to the subject an effective amount of the oligonucleotide conjugate according to claim 2 .

10 . A method for inhibiting APOC3 protein expression in a subject, comprising administering to the subject an effective amount of the antisense oligomer, pharmaceutically acceptable salt thereof or pharmaceutically acceptable hydrate thereof according to claim 1 .