# US 8,785,407 B2 · Antisense antiviral agent and method for treating ssRNA viral infection

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

- Number: US 8,785,407 B2
- Document ID: US8785407B2
- Status: Granted
- Kind: B2
- Application number: 11/431,968
- Filed: 2006-05-10
- Published: 2007-11-15
- Granted: 2014-07-22
- Earliest claimed: 2006-05-10
- Assignees: Sarepta Therapeutics, Inc.
- Applicants: David A. Stein; Douglas E. Skilling; Patrick L. Iversen; Alvin W. Smith; Dwight D. Weller
- Inventors: David A. Stein; Douglas E. Skilling; Patrick L. Iversen; Alvin W. Smith; Dwight D. Weller
- Web page: https://patentgrep.com/patent/US8785407B2

## CPC

- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- 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)

## Abstract

The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds have morpholino subunits linked by uncharged phosphorodiamidate linkages interspersed with cationic phosphorodiamidate linkages.

## Claims

### Claim 1

A method of inhibiting infection by an HCV virus in a subject, comprising administering to the subject, a therapeutically effective amount of a morpholino oligonucleotide composed of 12 to 30 morpholino subunits that is substantially complementary to the target sequence set forth in SEQ ID NO:37, wherein the oligonucleotide has a Tm, with respect to binding to the target sequence of greater than about 50° C., and wherein the morpholino subunits are linked by uncharged phosphorodiamidate linkages interspersed with at least two and up to eight phosphorodiamidate linkages containing piperazine groups.

### Claim 2 (depends on 1)

The method of claim 1, wherein said morpholino subunits are joined by phosphorodiamidate linkages, in accordance with the structure:
where Y1=O, Z=O, Pj is a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide (where base-pairing moieties on different subunits may be the same or different), and X is alkyl, alkoxy, thioalkoxy, or alkyl amino of the form NR2, where each R is independently hydrogen or methyl, for the uncharged linkages, and the phosphorodiamidate linkages containing piperazine groups are represented by the same structure, but where X is 1-piperazino.

### Claim 3 (depends on 1)

The method of claim 1, wherein the oligonucleotide is actively taken up by mammalian cells.

### Claim 4 (depends on 1)

The method of claim 1, wherein the oligonucleotide is complementary to at least 8 contiguous bases of SEQ ID NO:15.

### Claim 5 (depends on 1)

The method of claim 1, wherein an arginine-rich peptide is linked covalently to the 5′ or 3′ end of the oligonucleotide.

### Claim 6 (depends on 5)

The method of claim 5, wherein the arginine-rich peptide is about 8-16 amino acids.

### Claim 7 (depends on 5)

The method of claim 5, wherein the arginine-rich peptide is selected from SEQ ID NOS:41-43.

### Claim 8 (depends on 1)

The method of claim 1, wherein the oligonucleotide is composed of 12 to 25 morpholino subunits.

### Claim 9 (depends on 8)

The method of claim 8, wherein the oligonucleotide is complementary to at least 12 contiguous bases of SEQ ID NO:37.

### Claim 10 (depends on 1)

The method of claim 1, wherein the oligonucleotide is complementary to at least 15 contiguous bases of SEQ ID NO:37.

### Claim 11 (depends on 1)

The method of claim 1, wherein the oligonucleotide is composed of 15 to 22 subunits and is 100% complementary to SEQ ID NO:37.

### Claim 12 (depends on 2)

The method of claim 2, wherein X is alkyl amino of the form NR2, where R is methyl, and where the phosphorodiamidate linkages containing piperazine groups are represented by the same structure, but where X is 1-piperazino.