# US 9,834,824 B2 · Metapneumovirus strains and their use in vaccine formulations and as vectors for expression of antigenic sequences

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- Number: US 9,834,824 B2
- Document ID: US9834824B2
- Status: Granted
- Kind: B2
- Application number: 15/404,854
- Filed: 2017-01-12
- Published: 2017-05-18
- Granted: 2017-12-05
- Earliest claimed: 2002-02-21
- Assignees: Erasmus University Medical Center Rotterdam
- Applicants: Erasmus University Medical Center Rotterdam
- Inventors: Ronaldus Adrianus Maria Fouchier; Bernadetta Gerarda Van Den Hoogen; Albertus Dominicus Marcellinus Erasmus Osterhaus; Jan Cornelius De Jong; Jan Groen
- Web page: https://patentgrep.com/patent/US9834824B2

## CPC

- C12Q 1/701: {Specific hybridization probes}
- A61K 39/12: Viral antigens
- A61K 39/155: Paramyxoviridae, e.g. parainfluenza virus
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 19/00: Drugs for skeletal disorders
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/16: for influenza or rhinoviruses
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- C07K 16/11: Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/5011: {for testing antineoplastic activity}
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/5088: {of vertebrates}
- G01N 33/56983: {Viruses}
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/552: {Veterinary vaccine}
- A61K 2039/58: {raising an immune response against a target which is not the antigen used for immunisation}
- A61K 2039/70: {Multivalent vaccine}
- A61K 2123/00: Preparations for testing in vivo
- C12N 2710/22034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18321: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/18322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/18334: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18343: viral genome or elements thereof as genetic vector
- C12N 2760/18522: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/18534: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18621: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/18622: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/18634: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18643: viral genome or elements thereof as genetic vector
- C12N 2840/203: having an IRES
- C12Q 2600/158: Expression markers
- G01N 2333/08: RNA viruses
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Provided is an isolated mammalian negative strand RNA virus, metapneumovirus (MPV), within the sub-family Pneumoviridae, of the family Paramyxoviridae. Also provided are isolated mammalian negative strand RNA viruses identifiable as phylogenetically corresponding or relating to the genus Metapneumovirus and components thereof. In particular, provided is a mammalian MPV, subgroups and variants thereof. Also provided are genomic nucleotide sequences of different isolates of mammalian MPV, in particular, human MPV. Disclosed is the use of the sequence information of different isolates of mammalian MPV for diagnostic and therapeutic methods. Provided are nucleotide sequences encoding the genome of an MPV or a portion thereof, including both mammalian and avian MPV. Further described are chimeric or recombinant viruses encoded by the nucleotide sequences and chimeric and recombinant mammalian MPV that comprise one or more non-native or heterologous sequences. Also provided are vaccine formulations comprising mammalian or avian MPV, including recombinant and chimeric forms thereof. The vaccine preparations encompass multivalent vaccines, including bivalent and trivalent vaccine preparations.

## Claims

### Claim 1

A kit for determining the presence of metapneumovirus (MPV) in a mammalian subject, the kit comprising:
a DNA probe of at least 10 nucleotides that specifically hybridizes to a target polynucleotide,
wherein the DNA probe does not specifically hybridize to a polynucleotide from avian pneumovirus (APV);
wherein the probe does not hybridize under stringent conditions to a sequence encoding a polypeptide of SEQ ID NOs:366 and 368 or the complement of the sequence;
wherein the stringent conditions includes a hybridization buffer comprising 6×SSC and 1mM EDTA; and
wherein the target polynucleotide comprises a first nucleic acid encoding a polypeptide that is at least 90% identical to SEQ ID NO:367 or the complement of the first nucleic acid; or
wherein the target polynucleotide comprises a second nucleic acid encoding a polypeptide that is at least 90% identical to SEQ ID NO:369 or the complement of the second nucleic acid.

### Claim 2 (depends on 1)

The kit of claim 1, wherein the DNA probe comprises at least 25 nucleotides.

### Claim 3 (depends on 1)

The kit of claim 1, wherein the DNA probe comprises at least 40 nucleotides.

### Claim 4 (depends on 1)

The kit of claim 1, wherein the DNA probe further comprises a detectable marker.

### Claim 5 (depends on 1)

The kit of claim 1, wherein the target polynucleotide comprises a nucleic acid encoding SEQ ID NO:367 or wherein the target polynucleotide comprises a nucleic acid encoding SEQ ID NO:369.