# US 2002/0086033 A1 · Pestivirus mutants and vaccines containing the same

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- Number: US 2002/0086033 A1
- Document ID: US20020086033A1
- Status: Published application
- Kind: A1
- Application number: 09/839,796
- Filed: 2001-04-19
- Published: 2002-07-04
- Earliest claimed: 2000-04-21
- Assignees: Akzo Nobel N.V.
- Inventors: Heinz-Jurgen H.J. Thiel; Paul P. Becher; Michaela M. Orlich
- Web page: https://patentgrep.com/patent/US20020086033A1

## CPC

- A61K 39/12: Viral antigens
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/552: {Veterinary vaccine}
- C12N 2770/24322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2770/24334: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2770/24362: by genetic engineering
- C12N 2770/24364: by serial passage
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention is directed to attenuated pestivirus mutants, which have a reduced ability to replicate as exhibited by a small plaque size. The mutations are in the 5′ nontranslated region of the viral genome. These mutant viruses are useful as live vaccines in the control of bovine viral diarrhea, border disease and classical swine fever.

## Claims

### Claim 1

A pestivirus which contains one or more mutations in the region containing stem-loops la and lb of the 5′ nontranslated region (NTR) of the pestivirus genome, which mutation results in a small plaque size phenotype, and in which the expression of the viral polyprotein is under the control of a homologous internal ribosome entry site (IRES) and the sequence at the 5′ end of the genome is GUAU.

### Claim 2 (depends on 1)

The pestivirus according to claim 1, characterised in that the pestivirus has more than one mutation in the 5′ NTR.

### Claim 3 (depends on 1)

The pestivirus according to claim 1, characterised in that the mutation is a deletion of one or more nucleotides.

### Claim 4 (depends on 3)

The pestivirus according to claim 3, characterised in that the mutation is a deletion of stem-loop la.

### Claim 5 (depends on 4)

The pestivirus according to claim 4, characterised in that the mutation is a deletion of stem-loop la and part of stem-loop lb.

### Claim 6 (depends on 4)

The pestivirus according to claim 4, characterised in that the mutation is a deletion of stem-loops la and lb, provided that the 5′ terminal sequence is GUAUAU or GUAUCCU.

### Claim 7 (depends on 1, 2, 3, 4)

The pestivirus according to claims 1-4, characterised in that if the loop portion of stem-loop lb is present, then the loop consists of five adenosine (A) residues.

### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7)

The pestivirus according to claims 1-7, characterised in that the pestivirus is BVDV-1 or BVDV-2.

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

A vaccine comprising a live attenuated pestivirus according to claims 1-8, and a pharmaceutically acceptable carrier or diluent.

### Claim 10 (depends on 9)

The vaccine according to claim 9, which contains an adjuvant.

### Claim 11 (depends on 9)

The vaccine according to claim 9, which is in freeze-dried or frozen form.

### Claim 12 (depends on 9)

The vaccine according to claim 9, which comprises an live attenuated BVDV and an immunogen derived from one or more of bovine rotavirus, bovine respiratory syncytial virus, bovine herpesvirus type 1, bovine coronaviruses, parainfluenza type 3 virus, bovine paramyxovirus, foot and mouth disease virus, infectious bovine rhinotracheitis virus and Pasteurella hemolytica.

### Claim 13 (depends on 9, 10, 11, 12)

A method of immunizing against a pestivirus-induced disease, comprising administering to an animal the vaccine according to claims 9-12.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

A method of making a vaccine for the protection of an animal against a pestivirus, comprising mixing together a pestivirus according to claims 1-8 with a pharmaceutically acceptable carrier.
