# US 10,501,740 B2 · Compositions and methods for inhibiting expression of factor V

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- Number: US 10,501,740 B2
- Document ID: US10501740B2
- Status: Granted
- Kind: B2
- Application number: 15/676,874
- Filed: 2017-08-14
- Published: 2018-05-10
- Granted: 2019-12-10
- Earliest claimed: 2005-11-09
- Assignees: Alnylam Pharmaceuticals, Inc.
- Applicants: Alnylam Pharmaceuticals, Inc.
- Inventors: Hans-Peter Vornlocher; John M. Maraganore
- Web page: https://patentgrep.com/patent/US10501740B2

## CPC

- C12N 15/113: 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)}
- A61K 47/554: {the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/30: Special therapeutic applications
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 4)

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.

### Claim 6 (depends on 4)

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.

### Claim 7 (depends on 1)

An isolated cell comprising the dsRNA of claim 1.

### Claim 8 (depends on 7)

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

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 10)

A cell comprising the vector of claim 10.

### Claim 12 (depends on 11)

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

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 13)

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