US 11,918,600 B2
Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
Hongyan Zhang, Kunshan (CN); Shan Gao, Kunshan (CN); Daiwu Kang, Kunshan (CN); and Gengrong Chen, Kunshan (CN)
Assigned to SUZHOU RIBO LIFE SCIENCE CO., LTD., Kunshan (CN)
Appl. No. 17/269,039
Filed by SUZHOU RIBO LIFE SCIENCE CO., LTD., Kunshan (CN)
PCT Filed Aug. 20, 2019, PCT No. PCT/CN2019/101656
§ 371(c)(1), (2) Date Feb. 17, 2021,
PCT Pub. No. WO2020/038377, PCT Pub. Date Feb. 27, 2020.
Claims priority of application No. 201810951752.4 (CN), filed on Aug. 21, 2018; and application No. 201811165363.5 (CN), filed on Sep. 30, 2018.
Prior Publication US 2021/0275564 A1, Sep. 9, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/113 (2010.01); A61K 31/7088 (2006.01); A61K 31/712 (2006.01); A61K 31/713 (2006.01); A61K 47/18 (2017.01); A61K 47/54 (2017.01)
CPC A61K 31/7088 (2013.01) [A61K 31/712 (2013.01); A61K 31/713 (2013.01); A61K 47/18 (2013.01); A61K 47/543 (2017.08); C12N 15/113 (2013.01); C12N 15/1131 (2013.01); C12N 2310/11 (2013.01); C12N 2310/14 (2013.01); C12N 2310/322 (2013.01); C12N 2320/32 (2013.01)] 40 Claims
OG exemplary drawing
 
1. A siRNA capable of inhibiting the expression of an HBV gene, comprising a sense strand and an antisense strand, wherein each nucleotide in the sense strand and the antisense strand is a modified nucleotide, wherein the sense strand and the antisense strand both comprise fluoro modified nucleotides and non-fluoro modified nucleotides; a “fluoro modified nucleotide” refers to a nucleotide formed by substituting the 2′-hydroxy of the ribose group of the nucleotide with a fluoro group, and a “non-fluoro modified nucleotide” refers to a nucleotide formed by substituting the 2′-hydroxy of the ribose group of the nucleotide with a non-fluoro group, or a nucleotide analogue; the sense strand comprises a nucleotide sequence 1; the antisense strand comprises a nucleotide sequence 2; the nucleotide sequence 1 and the nucleotide sequence 2 are at least partly reverse complementary to form a double-stranded region; wherein the nucleotide sequence 1 and the nucleotide sequence shown in SEQ ID NO: 1 have an equal length and no more than 3 nucleotide differences; and the nucleotide sequence 2 and the nucleotide sequence shown in SEQ ID NO: 2 have an equal length and no more than 3 nucleotide differences:
5′-GAAAGUAUGUCAACGAAUZ-3′  (SEQ ID NO: 1),
5′-Z′AUUCGUUGACAUACUUUC-3′  (SEQ ID NO: 2),
wherein Z is U, Z′ is A;
the nucleotide sequence 1 comprises a nucleotide ZA at the position corresponding to Z; the nucleotide sequence 2 comprises a nucleotide Z′B at the position corresponding to Z′; the nucleotide Z′B is the first nucleotide from 5′ terminal of the antisense strand; and
the fluoro modified nucleotides are located within the nucleotide sequence 1 and the nucleotide sequence 2; wherein in the direction from 5′ terminal to 3′ terminal, the nucleotides at positions 7, 8 and 9 in the sense strand of the nucleotide sequence 1 are fluoro modified nucleotides; the nucleotides at positions 2, 6, 14 and 16 in the antisense strand of the nucleotide sequence 2 are fluoro modified nucleotides; and the nucleotides at the other positions in the antisense strand and sense strand are non-fluoro modified nucleotides.