公开(公告)号：US20220395526A1

公开(公告)日：2022-12-15

申请号：US16765799

申请日：2018-11-29

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang

IPC: A61K31/713 ,  A61K47/54 ,  A61P31/20

Abstract: Provided are a siRNA for inhibiting the expression of hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is independently a modified nucleotide. The siRNA comprises a sense strand and an antisense strand. The sense strand of the siRNA comprises a nucleotide sequence 1 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 155, and the antisense strand of the siRNA comprises a nucleotide sequence 2 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 156.

公开(公告)号：US11918600B2

公开(公告)日：2024-03-05

申请号：US17269039

申请日：2019-08-20

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang ,  Gengrong Chen

IPC: C12N15/113 ,  A61K31/7088 ,  A61K31/712 ,  A61K31/713 ,  A61K47/18 ,  A61K47/54

CPC classification number: A61K31/7088 ,  A61K31/712 ,  A61K31/713 ,  A61K47/18 ,  A61K47/543 ,  C12N15/113 ,  C12N15/1131 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2320/32

Abstract: Provided is a siRNA for inhibiting HBV gene expression, including a sense strand and an antisense strand. The sense strand includes a nucleotide sequence 1, and the antisense strand includes a nucleotide sequence 2; the nucleotide sequence 1 and the nucleotide sequence 2 are at least partially reversely complementary to form a double-stranded region; the nucleotide sequence 1 and the nucleotide sequence shown in SEQ ID NO: 1 are equal in length, and no more than 3 nucleotide differences are generated; the nucleotide sequence 2 and the nucleotide sequence shown in SEQ ID NO: 2 are equal in length, and no more than 3 nucleotide differences are generated; nucleotides of the 7th, 8th, and 9th bits of the nucleotide sequence 1 and the 2nd, 6th, 14th, and 16th of the nucleotide sequence 2 are fluoro-modified nucleotides. Also provided are a pharmaceutical composition and a conjugate containing the siRNA.

公开(公告)号：US11660347B2

公开(公告)日：2023-05-30

申请号：US16758532

申请日：2018-11-29

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang

IPC: A61K47/54 ,  A61P3/06 ,  A61K31/713 ,  C12N15/113 ,  C07H1/00

CPC classification number: A61K47/549 ,  A61K31/713 ,  A61P3/06 ,  C07H1/00 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/351

Abstract: The present disclosure provides a siRNA for inhibiting the expression of apolipoprotein C3 (ApoC3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

公开(公告)号：US11414661B2

公开(公告)日：2022-08-16

申请号：US16764307

申请日：2018-11-29

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang ,  Lina Kong

IPC: C12N15/113 ,  A61P3/06

Abstract: Provided are a siRNA for inhibiting the expression of an angiopoietin-like protein 3 (ANGPTL3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

公开(公告)号：US09549986B2

公开(公告)日：2017-01-24

申请号：US14354496

申请日：2012-10-23

Applicant: Suzhou Ribo Life Science Co., Ltd.

Inventor： Hongyan Zhang ,  Jun Wang

IPC: A61K47/34 ,  C08G79/04 ,  C12N15/113 ,  C08G63/08 ,  A61K9/107 ,  A61K9/51 ,  A61K31/7105 ,  A61K31/713 ,  C12N15/11

CPC classification number: A61K47/34 ,  A61K9/1075 ,  A61K9/5153 ,  A61K31/7105 ,  A61K31/713 ,  C08G63/08 ,  C08G79/04 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/32

Abstract: Provided are a polycaprolactone-polyphosphate block copolymer, a liquid composite formed by the block copolymer, a nucleic acid preparation, preparation methods for the copolymer and the liquid composite, and the use of the copolymer and the liquid composite in a nucleic acid medicine delivery system. The block copolymer prepared using the present invention has good biocompatibility, low cytotoxicity, and good biodegradability. The micelles provided in the present invention self-assemble into nano-particles in an aqueous solution, and have good stability, biocompatibility, and biodegradability, and low cytotoxicity. The preparation method is simple, has high repeatability, as a vector can protect small nucleic acids such as siRNA from biodegradation, can combine with the scale effect of nano-particles, and can be used for treating different diseases. Additionally, bonding targeting groups enable specificity recognition of different cancer cells.

Abstract translation: 提供了聚己内酯 - 聚磷酸酯嵌段共聚物，通过嵌段共聚物形成的液体复合物，核酸制剂，共聚物和液体复合物的制备方法，以及在核酸药物递送系统中使用共聚物和液体复合物 。 使用本发明制备的嵌段共聚物具有良好的生物相容性，低细胞毒性和良好的生物降解性。 本发明提供的胶束在水溶液中自组装成纳米颗粒，具有良好的稳定性，生物相容性和生物降解性以及低的细胞毒性。 制备方法简单，重复性高，载体可以保护小核酸如siRNA免受生物降解，可与纳米颗粒的鳞屑结合，可用于治疗不同疾病。 另外，结合靶向组能够特异性识别不同的癌细胞。

公开(公告)号：US11414665B2

公开(公告)日：2022-08-16

申请号：US16763058

申请日：2018-11-29

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang

IPC: C12N15/11 ,  C12N15/113 ,  A61P31/20 ,  A61K31/713

Abstract: Provided are an siRNA for inhibiting expression of a Hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is an independently modified or unmodified nucleotide; the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A; the length of the nucleotide sequence A is the same as that of a nucleotide sequence as shown in SEQ ID NO: 1, and the number of the nucleotide differences is not more than three; the antisense strand comprises a nucleotide sequence B; and the length of the nucleotide sequence B is the same as that of a nucleotide sequence as shown in SEQ ID NO: 2, and number of nucleotide differences is not more than three.

公开(公告)号：US20150093444A1

公开(公告)日：2015-04-02

申请号：US14354496

申请日：2012-10-23

Applicant: Suzhou Ribo Life Science Co., Ltd.

Inventor： Hongyan Zhang ,  Jun Wang

IPC: A61K47/34 ,  C12N15/113 ,  C08G79/04

CPC classification number: A61K47/34 ,  A61K9/1075 ,  A61K9/5153 ,  A61K31/7105 ,  A61K31/713 ,  C08G63/08 ,  C08G79/04 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/32

Abstract: Provided are a polycaprolactone-polyphosphate block copolymer, a liquid composite formed by the block copolymer, a nucleic acid preparation, preparation methods for the copolymer and the liquid composite, and the use of the copolymer and the liquid composite in a nucleic acid medicine delivery system. The block copolymer prepared using the present invention has good biocompatibility, low cytotoxicity, and good biodegradability. The micelles provided in the present invention self-assemble into nano-particles in an aqueous solution, and have good stability, biocompatibility, and biodegradability, and low cytotoxicity. The preparation method is simple, has high repeatability, as a vector can protect small nucleic acids such as siRNA from biodegradation, can combine with the scale effect of nano-particles, and can be used for treating different diseases. Additionally, bonding targeting groups enable specificity recognition of different cancer cells.

Abstract translation: 提供了聚己内酯 - 聚磷酸酯嵌段共聚物，通过嵌段共聚物形成的液体复合物，核酸制剂，共聚物和液体复合物的制备方法，以及在核酸药物递送系统中使用共聚物和液体复合物 。 使用本发明制备的嵌段共聚物具有良好的生物相容性，低细胞毒性和良好的生物降解性。 本发明提供的胶束在水溶液中自组装成纳米颗粒，具有良好的稳定性，生物相容性和生物降解性以及低的细胞毒性。 制备方法简单，重复性高，载体可以保护小核酸如siRNA免受生物降解，可与纳米颗粒的鳞屑结合，可用于治疗不同疾病。 另外，结合靶向组能够特异性识别不同的癌细胞。

公开(公告)号：US12083142B2

公开(公告)日：2024-09-10

申请号：US16765799

申请日：2018-11-29

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang

IPC: A61K31/713 ,  A61K47/54 ,  A61P31/20

CPC classification number: A61K31/713 ,  A61K47/549 ,  A61P31/20

Abstract: Provided are a siRNA for inhibiting the expression of hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is independently a modified nucleotide. The siRNA comprises a sense strand and an antisense strand. The sense strand of the siRNA comprises a nucleotide sequence 1 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 155, and the antisense strand of the siRNA comprises a nucleotide sequence 2 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 156.

公开(公告)号：US11492620B2

公开(公告)日：2022-11-08

申请号：US16758720

申请日：2018-11-29

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang ,  Shan Gao ,  Daiwu Kang

IPC: C12N15/113 ,  A61P3/06

Abstract: Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5′ end to 3′ end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

公开(公告)号：US09593335B2

公开(公告)日：2017-03-14

申请号：US15130091

申请日：2016-04-15

Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD.

Inventor： Hongyan Zhang

IPC: C12N15/11 ,  C12N15/113

CPC classification number: C12N15/1137 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2320/30 ,  C12Y207/11021

Abstract: The present invention provides siRNAs for inhibiting the expression of plk1 gene, and the method for inhibiting the expression of plk1 gene in mammalian cells. The siRNAs of the present invention have the double-stranded structure, and said double-stranded structure is composed of the first single strand and the second single strand that are fully complementary, wherein the sequence of said first single strand is the same as the target sequence within the sequence as shown in SEQ ID NO: 1, and the sequence of said second single strand is complementary to the target sequence within the sequence as shown in SEQ ID NO: 1. The siRNAs of the present invention can sequence specifically mediate the inhibition of plk1 gene expression, and have a good serum stability. By the introduction of the siRNAs of the present invention into the tumor cells, the expression of plk1 gene can be effectively inhibited, and the growth of tumor cells is inhibited and the apoptosis of tumor cells is promoted.

Abstract translation: 本发明提供抑制plk1基因表达的siRNA，以及抑制哺乳动物细胞中plk1基因表达的方法。 本发明的siRNA具有双链结构，所述双链结构由完全互补的第一单链和第二单链组成，其中所述第一单链的序列与靶相同 SEQ ID NO：1所示的序列中的序列，并且所述第二单链的序列与SEQ ID NO：1所示的序列内的靶序列互补。本发明的siRNA可以特异性介导 抑制plk1基因表达，并具有良好的血清稳定性。 通过将本发明的siRNA引入肿瘤细胞中，可以有效抑制plk1基因的表达，抑制肿瘤细胞的生长，促进肿瘤细胞的凋亡。