Compositions and methods for inhibiting expression of factor V

Patent metadata

Field	Value
Publication number	US-9441225-B2
Application number	US-201414155239-A
Country	US
Kind code	B2
Filing date	Jan 14, 2014
Priority date	Nov 9, 2005
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

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) compound comprising a sense strand and an antisense strand, wherein the nucleotide sequence of the sense strand comprises the nucleotide sequence of SEQ ID NO: 3 and the nucleotide sequence of the antisense strand comprises the nucleotide sequence of SEQ ID NO: 4, respectively.

2. The dsRNA of claim 1 , wherein the sense strand consists of the nucleotide sequence of SEQ ID NO: 3 and the antisense strand consists of the nucleotide sequence of SEQ ID NO: 4, respectively.

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

4. The dsRNA of claim 3 , 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.

5. The dsRNA of claim 3 , 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.

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

7. The cell of claim 6 , wherein the cell is a mammalian cell.

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

9. 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.

10. The method of claim 9 , wherein the cell is a mammalian cell.

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

12. A cell comprising the vector of claim 11 .

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

14. The vector of claim 11 , comprising at least one regulatory sequence operably linked to at least one nucleotide sequence that encodes the sense strand and antisense strand of the dsRNA of claim 1 .

15. A cell comprising the vector of claim 14 .

16. The cell of claim 15 , wherein the cell is a mammalian cell.

17. A pharmaceutical composition comprising the dsRNA of claim 2 and a pharmaceutically acceptable carrier.

18. 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 3 ; 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.

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

• 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

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title