# US 9,370,562 B2 · Schmallenberg virus (SBV) vaccine, methods of production, and uses thereof

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- Number: US 9,370,562 B2
- Document ID: US9370562B2
- Status: Granted
- Kind: B2
- Application number: 13/904,752
- Filed: 2013-05-29
- Published: 2013-12-05
- Granted: 2016-06-21
- Earliest claimed: 2012-06-01
- Assignees: Boehringer Ingelheim Vetmedica GmbH
- Applicants: Veljko Nikolin; Konrad Stadler; Axel Lischewski; Alexander Brix; Jeffrey P. Knittel; Katharina Hedwig Toepfer
- Inventors: Veljko Nikolin; Konrad Stadler; Axel Lischewski; Alexander Brix; Jeffrey P. Knittel; Katharina Hedwig Toepfer
- Web page: https://patentgrep.com/patent/US9370562B2

## CPC

- A61K 39/12: Viral antigens
- A61K 35/76: Viruses; Subviral particles; Bacteriophages
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 37/04: Immunostimulants
- C07K 7/00: Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K 2039/5252: {inactivated (killed)}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/552: {Veterinary vaccine}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55577: {Saponins; Quil A; QS21; ISCOMS}
- C12N 2760/12021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/12022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/12034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/12063: by chemical treatment
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to the field of vaccines and medicaments for the prophylaxis and treatment of infectious diseases in ruminants. In particular, it relates to inactivated Schmallenberg virus (SBV) useful as vaccine or medicament for preventing or treating viremia, the transmission and clinical symptoms, in particular malformations in newborn ruminants such as cattle, sheep and goats, induced by SBV.

## Claims

### Claim 1

An immunogenic composition comprising saponin, aluminum hydroxide, and an aziridine compound-inactivated Schmallenberg virus (SBV), wherein the inactivated SBV comprises a medium (M) RNA segment having a sequence that is inverse complementary to a nucleic acid sequence having at least 95% sequence identity with the nucleic acid sequence of SEQ ID NO:2 over the whole length of SEQ ID NO:2.

### Claim 2 (depends on 1)

The immunogenic composition according to claim 1, wherein the inactivated SBV further comprises:
(a) a small (S) RNA segment having a sequence that is inverse complementary to the nucleic acid sequence of SEQ ID NO:7 over the whole length of SEQ ID NO:7;
(b) a medium (M) RNA segment that is inverse complementary to a nucleic acid sequence of SEQ ID NO:2 over the whole length of SEQ ID NO:2; and
(c) a large (L) RNA segment that is inverse complementary to a nucleic acid sequence of SEQ ID NO:3 over the whole length of SEQ ID NO:3.

### Claim 3 (depends on 1)

The immunogenic composition according to claim 1, wherein the aziridine compound is binary ethyleneimine (BEI).

### Claim 4 (depends on 1)

The immunogenic composition according to claim 1, comprising an amount of SBV which is equivalent to a virus titer of at least about 105 TCID50/mL per dose.

### Claim 5 (depends on 1)

The immunogenic composition according to claim 1, wherein the SBV has a pre-inactivation titer of at least about 106 SBV particles per milliliter.

### Claim 6 (depends on 1)

The immunogenic composition according to claim 1, further containing one or more pharmaceutically acceptable carriers or excipients.

### Claim 7 (depends on 6)

The immunogenic composition according to claim 6, wherein said one or more pharmaceutically acceptable carriers or excipients are selected from the group consisting of solvents, dispersion media, adjuvants, stabilizing agents, diluents, preservatives, antibacterial and antifungal agents, isotonic agents, and adsorption delaying agents.

### Claim 8 (depends on 1)

A vaccine composition for the treatment of Schmallenberg associated disease in an animal selected from the group consisting kyphosis, lordosis, scoliosis, and torticollis of the vertebral column macrocephaly and brachygnathia inferior of the scull; and hydracephaly, porencephaly, cerebellar hypoplasia, and hypoplasia of the brain stem comprising administration of a therapeutic dose to the animal in need thereof of the immunogenic composition according to claim 1.

### Claim 9 (depends on 1)

A vaccine composition for the reduction of the viremia or malformations induced by SBV comprising the immunogenic composition according to claim 1.

### Claim 10 (depends on 1)

A vaccine composition for the reduction of the transmission of SBV, which comprises the immunogenic composition according to claim 1.

### Claim 11 (depends on 1)

A method for the production of the immunogenic composition according to claim 1, comprising the steps of
(A) infecting cells with a SBV that comprises a medium (M) RNA segment having a sequence that is inverse complementary to a nucleic acid sequence having at least 95% sequence identity with the nucleic acid sequence of SEQ ID NO: 2 over the whole length of SEQ ID NO: 2;
(B) cultivating the infected cells;
(C) harvesting the SBV produced by said cells; and
(D) inactivating said viral particles an aziridine compound.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the cells are monkey kidney cells or BHK cells.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the monkey kidney cells are Ma104 cells or Ma104-AK cells, and the BHK cells are BHK-21 cells.

### Claim 14 (depends on 11)

The method according to claim 11, wherein the cells are infected with SBV at an MOI of 0.00001-0.01.

### Claim 15 (depends on 11)

The method according to claim 11, wherein the cells are infected with SBV at an MOI of 0.0001-0.001.

### Claim 16 (depends on 11)

The method according to claim 11, wherein the cells are cultivated in a medium comprising about 0% FCS.

### Claim 17 (depends on 11)

The method according to claim 11, wherein the cells are cultivated in a medium comprising about 1-10% FCS.

### Claim 18 (depends on 11)

The method according to claim 11, wherein the cells are cultivated in a medium comprising about 2-6% FCS.

### Claim 19 (depends on 11)

The method according to claim 11, wherein the cells are cultivated at a temperature of 25-38° C.