# US RE45,016 E1 · Development of mutations useful for attenuating dengue viruses and chimeric dengue viruses

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- Number: US RE45,016 E1
- Document ID: USRE45016E1
- Status: Granted
- Kind: E1
- Application number: 13/896,396
- Filed: 2013-05-17
- Granted: 2014-07-15
- Earliest claimed: 2001-05-22
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America, as represented by the Secretary of the Department of Health and Human Services
- Inventors: Stephen S. Whitehead; Brian R. Murphy; Kathryn A. Hanley; Joseph E. Blaney; Ching-Juh Lai
- Web page: https://patentgrep.com/patent/USRE45016E1

## Abstract

A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.

## Claims

### Claim 1

A temperature-sensitive, host-range restricted mutant flavivirus, designated mutant 200, 201, wherein said virus comprises charge-cluster-to-alanine mutations at amino acids 2687 and 2688 of the NS5 gene, where amino acid position is given for the polyprotein of dengue virus type 4.

### Claim 2 (depends on 1)

The flavivirus of claim 1, further comprising the Δ30 mutation.

### Claim 3 (depends on 1)

The flavivirus of claim 1, wherein the flavivirus is a dengue virus type 1.

### Claim 4 (depends on 1)

The flavivirus of claim 1, wherein the flavivirus is a dengue virus type 2.

### Claim 5 (depends on 1)

The flavivirus of claim 1, wherein the flavivirus is a dengue virus type 3.

### Claim 6 (depends on 1)

The flavivirus of claim 1, wherein the flavivirus is a dengue virus type 4.

### Claim 7 (depends on 1)

The flavivirus of claim 1, wherein the flavivirus is a chimeric virus.

### Claim 8 (depends on 7)

The chimeric virus of claim 7 having a dengue 1 backbone.

### Claim 9 (depends on 7)

The chimeric virus of claim 7 having a dengue 2 backbone.

### Claim 10 (depends on 7)

The chimeric virus of claim 7 having a dengue 3 backbone.

### Claim 11 (depends on 7)

The chimeric virus of claim 7 having a dengue 4 backbone.

### Claim 12 (depends on 1)

The flavivirus of claim 1, wherein the phenotype is temperature sensitivity in Vero cells or the human liver cell line HuH-7.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

A pharmaceutical composition comprising a pharmacologically acceptable vehicle and a flavivirus according to any of claims 1-12.