Compositions and methods for inhibiting expression of factor V

Patent metadata

Field	Value
Publication number	US-10501740-B2
Application number	US-201715676874-A
Country	US
Kind code	B2
Filing date	Aug 14, 2017
Priority date	Nov 9, 2005
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of Factor V, comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of Factor V. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of Factor V using the pharmaceutical composition; and methods for inhibiting the expression of Factor V in a cell.

First claim

We claim:

1. An isolated double-stranded ribonucleic acid (dsRNA) comprising a sense strand and an antisense strand and wherein the sense strand comprises at least 15 contiguous nucleotides of the nucleotide sequence of SEQ ID NO: 5 and the antisense strand comprises at least 15 contiguous nucleotides of the nucleotide sequence of SEQ ID NO: 6 respectively, wherein the dsRNA comprises a duplex structure at least 15 base pairs in length; and wherein the sense strand and the antisense strand are between 15 and 30 base pairs in length.

2. The dsRNA of claim 1 , wherein the duplex structure is 19 base pairs in length.

3. The dsRNA of claim 1 , wherein the sense strand consists of the nucleotide sequence of SEQ ID NO: 5 and the antisense strand consists of the nucleotide sequence of SEQ ID NO: 6, respectively.

4. The dsRNA of claim 1 , wherein the dsRNA comprises at least one modified nucleotide.

5. The dsRNA of claim 4 , wherein said modified nucleotide is chosen from the group of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.

6. The dsRNA of claim 4 , wherein said modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.

7. An isolated cell comprising the dsRNA of claim 1 .

8. The cell of claim 7 , wherein the cell is a mammalian cell.

9. A pharmaceutical composition comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.

10. A vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of claim 1 .

11. A cell comprising the vector of claim 10 .

12. The cell of claim 11 , wherein the cell is a mammalian cell.

13. A method for inhibiting the expression of a Factor V gene in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 1 ; and
(b) maintaining the cell for a time sufficient to obtain degradation of the mRNA transcript of the Factor V gene, thereby inhibiting the expression of the Factor V gene in the cell.

14. The method of claim 13 , wherein the cell is a mammalian cell.

Assignees

• Alnylam Pharmaceuticals Inc

Inventors

• Vornlocher Hans-Peter
• Maraganore John M

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61K47/554

  the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid · CPC title

• 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

• C12N2310/14

  interfering nucleic acids [NA] · CPC title