Serpina1 siRNAs: compositions of matter and methods of treatment

Patent metadata

Field	Value
Publication number	US-9879261-B2
Application number	US-201514974650-A
Country	US
Kind code	B2
Filing date	Dec 18, 2015
Priority date	Jun 23, 2011
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

The technology described herein relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the Serpina1 gene, and methods of using such dsRNA compositions to inhibit expression of Serpina1.

First claim

What is claimed herein is:

1. A method of inhibiting Serpina1 expression in a cell, the method comprising:
(a) introducing into the cell a double-stranded ribonucleic acid (dsRNA) comprising a sense strand having the sequence of SEQ ID NO: 129 and an antisense strand having the sequence of SEQ ID NO: 173; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a Serpina1 gene, thereby inhibiting expression of the Serpina1 gene in the cell.

2. The method of claim 1 , wherein the Serpina1 expression is inhibited by at least 30%.

3. A method of treating a disorder mediated by Serpina1 expression comprising administering to a patient in need of such treatment a therapeutically effective amount of a double-stranded ribonucleic acid (dsRNA) comprising a sense strand having the sequence of SEQ ID NO: 129 and an antisense strand having the sequence of SEQ ID NO: 173.

4. The method of claim 3 , wherein the disorder is Alpha 1 anti-trypsin deficiency liver disease.

5. The method of claim 3 , wherein the administration of the dsRNA to the subject causes a decrease in cirrohsis, fibrosis, and/or Serpina1 protein accumulation in the liver.

6. The method of claim 3 , wherein the likelihood of hepatocellular carcinoma occurring in the patient is reduced.

7. The method of claim 3 , wherein the dsRNA is administered at a concentration of 0.01 mg/kg-5 mg/kg bodyweight of the patient.

Assignees

• Alnylam Pharmaceuticals Inc

Inventors

• Sehgal Alfica
• Bumcrot David
• Bettencourt Brian

Classifications

• C12N15/113 Primary

  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

• G03G15/556 Primary

  for toner consumption, e.g. pixel counting, toner coverage detection or toner density measurement · CPC title

• G03G2215/0888

  Arrangements for detecting toner level or concentration in the developing device · CPC title

• G03G15/086

  the level being measured by electro-magnetic means · CPC title

• C12N2310/3521

  Methyl · CPC title