US 12,274,752 B2
Nucleic acid, composition and conjugate containing same, preparation method, and use thereof
Hongyan Zhang, Suzhou (CN); Shan Gao, Suzhou (CN); and Daiwu Kang, Suzhou (CN)
Assigned to SUZHOU RIBO LIFE SCIENCE CO., LTD., Kunshan (CN)
Filed by SUZHOU RIBO LIFE SCIENCE CO., LTD., Suzhou (CN)
Filed on Apr. 17, 2023, as Appl. No. 18/301,845.
Application 18/301,845 is a continuation of application No. 16/758,532, granted, now 11,660,347, previously published as PCT/CN2018/118232, filed on Nov. 29, 2018.
Claims priority of application No. 201711249345.0 (CN), filed on Dec. 1, 2017; and application No. 201711486999.5 (CN), filed on Dec. 29, 2017.
Prior Publication US 2023/0355775 A1, Nov. 9, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/54 (2017.01); A61K 31/713 (2006.01); A61P 3/06 (2006.01); C07H 1/00 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/549 (2017.08) [A61K 31/713 (2013.01); A61P 3/06 (2018.01); C07H 1/00 (2013.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/344 (2013.01); C12N 2310/346 (2013.01); C12N 2310/351 (2013.01)] 26 Claims
OG exemplary drawing
 
1. A modified siRNA, comprising a sense strand and an antisense strand, wherein each of the nucleotides in the sense strand and in 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, the sense strand comprises a nucleotide sequence I and the antisense strand comprises a nucleotide sequence II, said nucleotide sequence I and said nucleotide sequence II being at least partly reverse complementary to form a double-strand region, wherein the nucleotide sequence I comprises a nucleotide sequence represented by SEQ ID NO:60, and the nucleotide sequence II comprises a nucleotide sequence represented by SEQ ID NO:61:
5′-CAAUAAAGCUGGACAAGAZA-3′ (SEQ ID NO: 60);
5′-Z′BUCUUGUCCAGCUUUAUUG-3′ (SEQ ID NO: 61),
wherein, ZA is selected from A, U, G, or C, and Z′B is the first nucleotide at the 5′ terminal of the antisense strand and complementary to ZA;
wherein the fluoro modified nucleotides are present in nucleotide sequence 60 and nucleotide sequence 61; in the direction from 5′ terminal to 3′ terminal, the nucleotides at positions 7, 8 and 9 of nucleotide sequence represented by SEQ ID NO:60 are fluoro modified nucleotides and the nucleotides at the other positions in the sense strand are non-fluoro modified nucleotides; and in the direction from 5′ terminal to 3′ terminal, the nucleotides at positions 2, 6, 14 and 16 of nucleotide sequence represented by SEQ ID NO:61 are fluoro modified nucleotides, and the nucleotides at the other positions in the antisense strand are non-fluoro modified nucleotides;
wherein “non-fluoro modified nucleotide” refers to a nucleotide formed by replacing 2′-hydroxy of the ribose group with a non-fluoro group, or a nucleotide analogue.