# US 9,777,043 B2 · Compositions and methods for treatment of cytomegalovirus

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- Number: US 9,777,043 B2
- Document ID: US9777043B2
- Status: Granted
- Kind: B2
- Application number: 14/357,423
- Filed: 2012-11-09
- Published: 2014-10-16
- Granted: 2017-10-03
- Earliest claimed: 2011-11-11
- Assignees: Variation Biotechnologies Inc.
- Applicants: Variation Biotechnologies, Inc.
- Inventors: David E. Anderson; Anne-Catherine Fluckiger
- Web page: https://patentgrep.com/patent/US9777043B2

## CPC

- A61K 39/12: Viral antigens
- C07K 14/005: from viruses
- A61K 39/245: Herpetoviridae, e.g. herpes simplex virus
- A61P 31/22: for herpes viruses
- A61K 2039/5258: {Virus-like particles}
- A61K 2039/70: {Multivalent vaccine}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/03: containing a transmembrane segment
- C12N 2710/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/13023: Virus like particles [VLP]
- C12N 2760/20234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/20245: Special targeting system for viral vectors
- 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)
- 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
- 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 disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

## Claims

### Claim 1

A virus like particle (VLP) comprising:
a fusion protein comprising an N-terminal portion of a gag protein found in a murine leukemia virus (MLV) fused upstream of a pp65 protein found in HCMV; and
a polypeptide comprising a glycoprotein (gB) protein found in HCMV.

### Claim 2 (depends on 1)

The VLP of claim 1, wherein the N-terminal portion of the gag protein does not comprise a C-terminal polymerase sequence found in MLV.

### Claim 3 (depends on 1)

The VLP of claim 1, wherein the N-terminal portion of the gag protein comprises the amino acid sequence of SEQ ID NO:1.

### Claim 4 (depends on 1)

The VLP of claim 1, wherein the N-terminal portion of the gag protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:1.

### Claim 5 (depends on 1)

The VLP of claim 1, wherein the polypeptide comprising the gB protein comprises the amino acid sequence of SEQ ID NO:7.

### Claim 6 (depends on 1)

The VLP of claim 1, wherein the polypeptide comprising the gB protein comprises at least 15 consecutive residues of SEQ ID NO:7.

### Claim 7 (depends on 1)

The VLP of claim 1, wherein the polypeptide comprising the gB protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:7.

### Claim 8

A VLP comprising:
a fusion protein comprising an amino acid sequence at least 85% identical to SEQ ID NO:4.; and
a polypeptide comprising an amino acid sequence at least 85% identical to SEQ ID NO:7.

### Claim 9 (depends on 8)

The VLP of claim 8, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO:4, and the polypeptide comprises the amino acid sequence of SEQ ID NO:7.

### Claim 10 (depends on 1, 8)

A pharmaceutical composition comprising the VLP of any one of claims 1 and 8, and a pharmaceutically acceptable carrier.

### Claim 11 (depends on 10)

The pharmaceutical composition of claim 10, further comprising an adjuvant selected from the group consisting of a cytokine, a gel-type adjuvant, a microbial adjuvant, an oil-emulsion adjuvant, an emulsifier-based adjuvant, a particulate adjuvant, a synthetic adjuvant, a polymer adjuvant, and a combination thereof.

### Claim 12

A method for the production of a VLP, the method comprising:
co-transfecting a host cell with a vector comprising a nucleotide sequence encoding an MLV gag-HCMV pp65 fusion protein, wherein the gag protein is fused upstream of the pp65 protein, and a vector comprising a nucleotide sequence encoding a gB polypeptide found in HCMV; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.

### Claim 13 (depends on 10)

A method for reducing frequency or severity or delaying onset of symptoms of HCMV infection in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 10.