Compositions and methods directed to treating liver fibrosis

Patent metadata

Field	Value
Publication number	US-9944671-B2
Application number	US-201113701551-A
Country	US
Kind code	B2
Filing date	Jun 2, 2011
Priority date	Jun 2, 2010
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the COL1A1, TGF-β, and SMAD2/3 genes, and methods of using such dsRNA compositions to inhibit expression of COL1A1, TGF-β, and SMAD2/3.

First claim

We claim:

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of COL1A1, wherein said dsRNA comprises a sense strand and an antisense strand, wherein the sense strand consists of SEQ ID NO: 53 and the antisense strand consists of SEQ ID NO: 54.

2. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of COL1A1, wherein said dsRNA comprises a modified sense strand and a modified antisense strand,
the sense strand comprising one of SEQ ID NOs:29, 33, 41, 45, 47, and 55, and the antisense strand comprising, respectively, one of SEQ ID NOs:30, 34, 42, 46, 48, and 56.

3. The dsRNA of claim 2 , wherein each strand is no more than 30 nucleotides in length.

4. The dsRNA of claim 2 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.

5. The dsRNA of claim 2 , further comprising a ligand.

6. A cell containing the dsRNA of claim 2 .

7. A lipid formulation comprising the dsRNA of claim 2 .

8. A vector encoding a dsRNA, wherein said dsRNA comprises a sense strand comprising a nucleobase sequence selected from the group consisting of SEQ ID NOs:29, 33, 41, 45, 47, and 55, an antisense strand comprising, respectively, a nucleobase sequence selected from the group consisting of SEQ ID NOs: 30, 34, 42, 46, 48, and 56, wherein the dsRNA is 30 or fewer base pairs in length, and wherein said dsRNA targets a COL1A1 mRNA for cleavage.

Assignees

• Hinkle Greg
• Kotelianski Victor
• Bettencourt Brian
• Sehgal Alfica
• Novobrantseva Tatiana
• Alnylam Pharmaceuticals Inc

Inventors

• Hinkle Greg
• Kotelianski Victor
• Bettencourt Brian
• Sehgal Alfica
• Novobrantseva Tatiana

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title