Patent ID: 11896674
Assignee: SUZHOU RIBO LIFE SCIENCE CO., LTD.
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 0:
1. A siRNA conjugate having the structure as shown by Formula (1):, wherein,
n1 is an integer of 1-3, and n3 is an integer of 0-4, and n1+n3≥2;
m1, m2, and m3 independently of one another are an integer of 2-10;
R10, R11, R12, R13, R14 and R15 independently of one another are one of H, methyl or ethyl;
R3 is a group having the structure as shown by Formula A59:, wherein E1 is OH, SH or BH2, and Nu is a siRNA;
each nucleotide in the siRNA is independently a modified or unmodified nucleotide; the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence 1, and the antisense strand comprises a nucleotide sequence 2; the nucleotide sequence 1 and nucleotide sequence 2 are at least partly reverse complementary to form a double-stranded region, wherein the nucleotide sequence 1 and the nucleotide sequence as shown by SEQ ID NO: 1 have an equal length and no more than 3 nucleotide differences, and the nucleotide sequence 2 and the nucleotide sequence as shown by SEQ ID NO: 2 have an equal length and no more than 3 nucleotide differences:, (SEQ ID NO: 1)

5′-GAAAGUAUGUCAACGAAUZ-3′;

 

(SEQ ID NO: 2)

5′-Z′AUUCGUUGACAUACUUUC-3′;

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′, wherein the Z′B is the first nucleotide at 5′ terminal of the antisense strand;
R2 is any group capable of linking to the N atom on the nitrogenous backbone and linking to A59;
each L1 is independently selected from the linkage combinations of one or more of Formulae A1-A26:, wherein j1 is an integer of 1-20;
j2 is an integer of 1-20;
R′ is a C1-C10 alkyl;
Ra is selected from one of Formulae A27-A45:, Rb is a C1-C10 alkyl; and
 represents the site where a group is covalently linked;
each M1 is independently selected from one of the ligands that have affinity to the asialoglycoprotein receptors (ASGP-R) on the surface of mammalian hepatocytes.