# US 6,077,510 A · Borna disease viral sequences, diagnostics and therapeutics for nervous system diseases

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- Number: US 6,077,510 A
- Document ID: US6077510A
- Status: Granted
- Kind: A
- Application number: 08/582,776
- Filed: 1996-01-04
- Granted: 2000-06-20
- Earliest claimed: 1995-01-06
- Assignees: The Regents of the University of California
- Inventors: W. Ian Lipkin; Thomas Briese; Stefanie Kliche; Patrick A. Schneider; Lothar Stitz; Annette Schneemann
- Web page: https://patentgrep.com/patent/US6077510A

## CPC

- C07K 14/005: from viruses
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 31/12: Antivirals
- A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/51: {comprising whole cells, viruses or DNA/RNA}
- C12N 2760/00022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/00043: viral genome or elements thereof as genetic vector
- Y10S 435/975: Kit
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention presents: genomic nucleotide sequence of Borna disease virus, nucleotide and amino acid sequences of Borna disease virus proteins, recombinant viral proteins, vectors and cells containing the sequences or encoding the proteins, ligand binding to these proteins such as antibodies, and the diagnostic and therapeutic uses of the foregoing.

## Claims

### Claim 1

A purified deglycosylated or unglycosylated gp18 polypeptide comprising an amino acid sequence of:
as set forth in SEQ ID NO:6.

### Claim 2

An isolated immunoreactive fragment of gp18 selected from the group consisting of:
a) amino acid position 1 to amino acid position 70 of unglycosylated gp18;
b) amino acid position 23 to amino acid position 142 of unglycosylated gp18;
c) amino acid 63 to amino acid position 142 of unglycosylated gp18;
d) amino acid position 100 to amino acid position 142 of unglycosylated gp18; and
e) fragments of the foregoing comprising at least four contiguous amino acids and at least one immunogenic epitope.

### Claim 3

An isolated immunoreactive fragment of gp18 selected from the group consisting of: SEQ ID NO:28 to SEQ ID NO:32.

### Claim 4 (depends on 1)

A composition comprising the polypeptide of claim 1.

### Claim 5 (depends on 2)

A composition comprising at least one immunoreactive fragment of claim 2, or 3.

### Claim 6

A method for detecting, in a sample, a ligand capable of binding a BDV protein, said method comprising the steps of:
a) contacting the sample with an isolated polypeptide selected from the group consisting of: unglycosylated recp18, unglycosylated polypeptides having the amino acid sequence of SEQ ID NO:6, and immunogenic fragments thereof; and
b) determining the presence or absence of a ligand which binds to the polypeptide.

### Claim 7 (depends on 6)

A method according to claim 6, further comprising the steps of:
a) contacting the sample with at least one other isolated polypeptide selected from the group consisting of p23, recp23, p40, recp40, p57, recp57, pol, recpol, and immunogenic fragments thereof; and
b) determining the presence or absence of a ligand which binds the other polypeptide.

### Claim 8

An immunoassay method for detecting, in a sample, an antibody immunoreactive with Borna disease virus, said method comprising the steps of:
a) contacting the sample with an isolated polypeptide, selected from the group consisting of gp18; recp18; polypeptides having the amino acid sequence of SEQ ID NO:6; and immunogenic fragments of the foregoing wherein the isolated polypeptide is prebound to a solid support without gel size fractionation; and
b) determining the presence or absence of an antibody which binds to the polypeptide.

### Claim 9

A method for selecting a ligand capable of binding gp18, said method comprising the steps of:
a) contacting the ligand with an isolated polypeptide selected from the group consisting of: unglycosylated recp18, unglycosylated polypeptides having the amino acid sequence of SEQ ID NO:6, and immunogenic fragments thereof; and
b) selecting for the ligand which binds to the polypeptide.

### Claim 10 (depends on 9)

A method according to claim 9, wherein said ligand is a monospecific antiserum and said selection step comprises eluting the ligand bound to the polypeptide.

### Claim 11 (depends on 9)

A method according to claim 9, wherein said ligand is a monoclonal antibody.

### Claim 12 (depends on 9)

A ligand, selected according to the method of claim 9, capable of binding a protein selected from the group consisting of: deglycosylated gp18, recp18, unglycosylated polypeptides having the amino acid sequence of SEQ ID NO:6, and fragments thereof which contain at least one immunogenic epitope.

### Claim 13 (depends on 12)

A ligand according to claim 12 selected from the group consisting of antisera, antibodies, F(ab').sub.2, and Fv fragments of antibodies.

### Claim 14

A panel comprising one or more purified polypeptides prebound to a solid support without gel size fractionation, wherein at least one of said polypeptides is selected from the group consisting of: gp18; recp18; polypeptides having the amino acid sequence of SEQ ID NO:6; and immunogenic fragments of the foregoing.

### Claim 15 (depends on 14)

A panel according to claim 14, comprising at least one other purified polypeptide prebound to a solid support without gel size fractionation, wherein the other purified polypeptide is selected from the group consisting of: p23, recp23, p40, recp40, p57, recp57, pol, recpol, and immunogenic fragments of the foregoing.

### Claim 16 (depends on 14)

A panel according to claim 14, wherein the solid support is selected from the group consisting of: microtiter wells, test tubes, beads, strips, membranes, and microparticles.

### Claim 17

A kit for use in a method of determining the presence or absence of a ligand that can bind gp18, said kit comprising:
a) a first container comprising a purified polypeptide selected from the group consisting of: gp18, recp18, polypeptides having the amino acid sequence of SEQ ID NO:6, and immunogenic fragments of gp18; and
b) a second container comprising another purified polypeptide selected from the group consisting of: p23, recp23, p40, recp40, p57, recp57, pol, recpol, and immunogenic fragments of the foregoing.

### Claim 18

A composition for eliciting an immune response comprising at least one component selected from the group consisting of: deglycosylated gp18, recp18, unglycosylated polypeptides having the amino acid sequence of SEQ ID NO:6, and immunogenic fragments of the foregoing, wherein said component is capable of inducing a cellular or humoral response in an organism administered the composition.

### Claim 19 (depends on 18)

A composition according to claim 18, wherein said component can induce the production of neutralizing antibody.
