# US 2014/0193483 A1 · Therapeutic vaccines for treating herpes simplex virus type-2 infections

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- Number: US 2014/0193483 A1
- Document ID: US20140193483A1
- Status: Published application
- Kind: A1
- Application number: 14/149,670
- Filed: 2014-01-07
- Published: 2014-07-10
- Earliest claimed: 2013-01-07
- Assignees: Biomedical Research Models, Inc.
- Applicants: Biomedical Research Models, Inc.
- Inventors: Kejian YANG; Dennis L. Guberski
- Web page: https://patentgrep.com/patent/US20140193483A1

## CPC

- A61K 39/12: Viral antigens
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/06: Antiasthmatics
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 31/04: Antibacterial agents
- A61P 31/22: for herpes viruses
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- 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 39/245: Herpetoviridae, e.g. herpes simplex virus
- A61K 2039/543: {intranasal}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- C07K 14/005: from viruses
- C07K 14/03: Herpetoviridae, e.g. pseudorabies virus
- C07K 14/035: Herpes simplex virus I or II
- C07K 16/085: Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
- C12N 2710/16634: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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 invention provides methods and kits for inducing a therapeutic immunity in animals (e.g. mammals) against viral antigens, including herpes-simplex virus type 2. In particular, the invention provides a method of treating animals with an established HSV-2 infection by administering a therapeutic vaccine comprising a priming dose of a nucleic acid encoding an HSV-2 antigen, an initial or first boosting dose comprising the protein form of the antigen encapsulated in liposomes, and one or more subsequent boosting doses comprising both the nucleic acid encoding the HSV-2 antigen and the liposomal-encapsulated protein antigen.

## Claims

### Claim 1

A method for treating an HSV-2 infection in a mammal comprising administering to the mammal:
(a) a priming preparation comprising a vector encoding an HSV-2 antigen under the control of a promoter;
(b) a first boosting preparation comprising the HSV-2 antigen encapsulated in liposomes; and
(c) a second boosting preparation comprising the vector encoding the HSV-2 antigen and the HSV-2 antigen encapsulated in liposomes,
wherein the vector is administered intramuscularly and the liposomal-encapsulated antigen is administered intranasally.

### Claim 2 (depends on 1)

The method of claim 1, wherein the priming preparation is administered in one or two administrations.

### Claim 3 (depends on 1)

The method of claim 1, wherein the first boosting preparation is administered to the mammal about 2 to 4 weeks after the priming preparation.

### Claim 4 (depends on 1)

The method of claim 1, wherein the first boosting preparation is administered to the mammal about 7 to 18 days after the priming preparation.

### Claim 5 (depends on 4)

The method of claim 4, wherein the first boosting preparation is administered to the mammal about 10 to 16 days after the priming preparation.

### Claim 6 (depends on 1)

The method of claim 1, wherein the second boosting preparation is administered to the mammal about 2 to 4 weeks after the first boosting preparation.

### Claim 7 (depends on 1)

The method of claim 1, wherein the second boosting preparation is administered to the mammal about 7 to 18 days after the first boosting preparation.

### Claim 8 (depends on 7)

The method of claim 7, wherein the second boosting preparation is administered to the mammal about 10 to 16 days after the first boosting preparation.

### Claim 9 (depends on 1)

The method of claim 1, further comprising administering to the mammal a combination of the vector encoding the HSV-2 antigen and the HSV-2 antigen encapsulated in liposomes at the sign of recurrence of herpatic lesions.

### Claim 10 (depends on 1)

The method of claim 1, wherein one or more symptoms of HSV-2 infection is ameliorated in the mammal following administration of the second boosting preparation.

### Claim 11 (depends on 10)

The method of claim 10, wherein the recurrence of herpatic lesions is reduced and/or completely prevented in the mammal as compared to an untreated mammal or a mammal vaccinated with a non-mucosal vaccine.

### Claim 12 (depends on 10)

The method of claim 10, wherein viral shedding is reduced in the mammal as compared to an untreated mammal or a mammal vaccinated with a non-mucosal vaccine.

### Claim 13 (depends on 1)

The method of claim 1, wherein antigen-specific IgA and IgG is increased in the vaginal secretions of the mammal as compared to an untreated mammal or a mammal vaccinated with a non-mucosal vaccine.

### Claim 14 (depends on 11, 12, 13)

The method of any one of claims 11 to 13, wherein the non-mucosal vaccine comprises a truncated HSV-2 gD protein formulated for subcutaneous administration.

### Claim 15 (depends on 1)

The method of claim 1, wherein the promoter is a cytomegalovirus promoter.

### Claim 16 (depends on 15)

The method of claim 15, wherein the cytomegalovirus promoter is an immediate early promoter.

### Claim 17 (depends on 1)

The method of claim 1, wherein the HSV-2 antigen encoded by the vector is codon-optimized for expression in mammalian cells.

### Claim 18 (depends on 1)

The method of claim 1, wherein the HSV-2 antigen encoded by the vector is codon-optimized for expression in human cells.

### Claim 19 (depends on 1)

The method of claim 1, wherein the HSV-2 antigen is a gD glycoprotein.

### Claim 20 (depends on 1)

The method of claim 1, wherein the vector encodes a full-length gD glycoprotein sequence.

### Claim 21 (depends on 20)

The method of claim 20, wherein the full-length gD glycoprotein sequence comprises a sequence of SEQ ID NO: 1.

### Claim 22 (depends on 1)

The method of claim 1, wherein the liposomal-encapsulated antigen in the first and second boosting preparations is an extracellular domain of a gD glycoprotein.

### Claim 23 (depends on 22)

The method of claim 22, wherein the antigen comprises a sequence of SEQ ID NO: 2.

### Claim 24 (depends on 1)

The method of claim 1, wherein the liposomes are anionic liposomes.

### Claim 25 (depends on 24)

The method of claim 24, wherein the liposomes have an average diameter of about 0.5-5 μm.

### Claim 26 (depends on 1)

The method of claim 1, wherein the mammal is human.