# US 7,745,418 B2 · Compositions and methods for inhibiting viral replication

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,745,418 B2
- Document ID: US7745418B2
- Status: Granted
- Kind: B2
- Application number: 11/959,936
- Filed: 2007-12-19
- Published: 2008-08-14
- Granted: 2010-06-29
- Earliest claimed: 2001-10-12
- Assignees: Alnylam Pharmaceuticals, Inc.
- Inventors: Matthias John; Stefan Limmer; Hans-Peter Vornlocher; Roland Kreutzer
- Web page: https://patentgrep.com/patent/US7745418B2

## CPC

- C12N 15/1131: {against viruses}
- A61P 31/14: for RNA viruses
- A61P 35/00: Antineoplastic agents
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/53: partially self-complementary or closed
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to a double-stranded ribonucleic acid (dsRNA) having a nucleotide sequence which is less that 30 nucleotides in length and which is substantially identical to at least a part of a 3′-untranslated region (3′-UTR) of a (+) strand RNA virus, such as HCV, as well as pharmaceutical compositions comprising the dsRNA, together with a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful for treating infections and diseases caused by the replication or activity of the (+) strand RNA virus, as well as methods for inhibiting viral replication.

## Claims

### Claim 1

A double-stranded ribonucleic acid (dsRNA) for inhibiting the replication of a (+) strand RNA virus, wherein the dsRNA comprises a sense RNA strand comprising a the nucleotide sequence of SEQ ID NO:4 and a complementary RNA strand comprising the nucleotide sequence of SEQ ID NO:5, and wherein the dsRNA is less than 30 base pairs in length.

### Claim 2 (depends on 1)

The dsRNA of claim 1, wherein the complementary nucleotide sequence is less than 25 nucleotides in length.

### Claim 3 (depends on 1)

The dsRNA of claim 1, wherein the complementary nucleotide sequence is 23 or 24 nucleotides in length.

### Claim 4 (depends on 1)

The dsRNA of claim 1, wherein the dsRNA comprises a blunt end.

### Claim 5 (depends on 1)

The dsRNA of claim 1, wherein the dsRNA comprises two blunt ends.

### Claim 6 (depends on 1)

The dsRNA of claim 1, wherein the complementary RNA strand and the sense RNA strand comprise a 3′-terminus and a 5′-terminus, and wherein at least one of said RNA strands comprises a nucleotide overhang of 1 to 3 nucleotides in length.

### Claim 7 (depends on 6)

The dsRNA of claim 6, wherein the nucleotide overhang is two nucleotides in length.

### Claim 8 (depends on 6)

The dsRNA of claim 6, wherein the nucleotide overhang is on the 3′-terminus of the complementary RNA strand.

### Claim 9 (depends on 6)

The dsRNA of claim 6, wherein the dsRNA further comprises a first end and a second end, wherein the first end comprises the 3′-terminus of the complementary RNA strand and the 5′-terminus of the sense RNA strand, and wherein the second end comprises the 5′-terminus of the complementary RNA strand and the 3′-terminus of the sense RNA strand, wherein the first end comprises a nucleotide overhang on the 3′-terminus of the complementary RNA strand, and wherein the second end is blunt.

### Claim 10 (depends on 9)

The dsRNA of claim 9, wherein the complementary RNA strand comprises a 2-nucleotide overhang at the 3′-terminus and wherein the second end of the dsRNA is blunt.

### Claim 11

A pharmaceutical composition for inhibiting the replication of a (+) strand RNA virus in an organism, comprising a dsRNA and a pharmaceutically acceptable carrier, wherein the dsRNA comprises a sense RNA strand comprising the nucleotide sequence of SEQ ID NO:4 and a complementary RNA strand comprising the nucleotide sequence of SEQ ID NO:5, and wherein the dsRNA is less than 30 base pairs in length.

### Claim 12 (depends on 11)

The pharmaceutical composition of claim 11, wherein the complementary nucleotide sequence is less than 25 nucleotides in length.

### Claim 13 (depends on 11)

The pharmaceutical compositions of claim 11, wherein the complementary nucleotide sequence is 23 or 24 nucleotides in length.

### Claim 14 (depends on 11)

The pharmaceutical composition of claim 11, wherein the dsRNA comprises a blunt end.

### Claim 15 (depends on 11)

The pharmaceutical composition of claim 11, wherein the dsRNA comprises two blunt ends.

### Claim 16 (depends on 11)

The pharmaceutical composition of claim 11, wherein the complementary RNA strand and the sense RNA strand comprise a 3′-terminus and a 5′-terminus, and wherein at least one of said RNA strands comprise a nucleotide overhang of 1 to 3 nucleotides in length.

### Claim 17 (depends on 16)

The pharmaceutical composition of claim 16, wherein the nucleotide overhang is two nucleotides in length.

### Claim 18 (depends on 16)

The pharmaceutical composition of claim 16, wherein the nucleotide overhang is on the 3′-terminus of the complementary RNA strand.

### Claim 19 (depends on 16)

The pharmaceutical composition of claim 16, wherein the dsRNA further comprises a first end and a second end, wherein the first end comprises the 3′-terminus of the complementary RNA strand and the 5′-terminus of the sense RNA strand, and wherein the second end comprises the 5′-terminus of the complementary RNA strand and the 3′-terminus of the sense RNA strand, wherein the first end comprises a nucleotide overhang on the 3′-terminus of the complementary RNA strand, and wherein the second end is blunt.

### Claim 20 (depends on 19)

The pharmaceutical composition of claim 19, wherein the complementary RNA strand comprises a 2-nucleotide overhang at the 3′-terminus and wherein the second end of the dsRNA is blunt.

### Claim 21 (depends on 11)

The pharmaceutical composition of claim 11, wherein a dosage unit of dsRNA is less than 5 milligram (mg) of dsRNA per kg body weight of the mammal.

### Claim 22 (depends on 11)

The pharmaceutical composition of claim 11, wherein a dosage unit of dsRNA is in a range of 0.01 to 2.5 milligrams (mg), 0.1 to 200 micrograms (μg), 0.1 to 100 μg per kilogram body weight of the mammal.

### Claim 23 (depends on 11)

The pharmaceutical composition of claim 11, wherein a dosage unit of dsRNA is less than 25 μg per kilogram body weight of the mammal.

### Claim 24 (depends on 11)

The pharmaceutical composition of claim 11, wherein the pharmaceutically acceptable carrier is an aqueous solution.

### Claim 25 (depends on 24)

The pharmaceutical composition of claim 24, wherein the aqueous solution is phosphate buffered saline.

### Claim 26 (depends on 11)

The pharmaceutical composition of claim 11, wherein the pharmaceutically acceptable carrier comprises a micellar structure selected from the group consisting of a liposome, capsid, capsoid, polymeric nanocapsule, and polymeric microcapsule.

### Claim 27 (depends on 11)

The pharmaceutical composition of claim 11, which is formulated to be administered by inhalation, infusion, injection, or orally.

### Claim 28 (depends on 11)

The pharmaceutical composition of claim 11, which is formulated to be administered by intravenous or intraperitoneal injection.