# US 2014/0193446 A1 · Biodegradable high-efficiency dengue vaccine, method for making the same, and pharmaceutical composition comprising the same

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- Number: US 2014/0193446 A1
- Document ID: US20140193446A1
- Status: Published application
- Kind: A1
- Application number: 13/924,793
- Filed: 2013-06-24
- Published: 2014-07-10
- Earliest claimed: 2013-01-09
- Assignees: National Cheng Kung University
- Applicants: National Cheng Kung University
- Inventors: YEE-SHIN LIN; YU-HUNG CHEN
- Web page: https://patentgrep.com/patent/US20140193446A1

## CPC

- A61K 39/12: Viral antigens
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 47/6921: {the form being a particulate, a powder, an adsorbate, a bead or a sphere}
- A61K 47/6933: {the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol}
- A61K 47/6939: {the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin}
- A61P 31/14: for RNA viruses
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/6031: {Proteins}
- A61K 2039/6093: {Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine}
- A61K 2039/64: {characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units}
- C12N 2770/24134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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
- 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 is related to a biodegradable high-efficiency dengue vaccine, a method for making the same, and a pharmaceutical composition comprising the same. The biodegradable high-efficiency dengue vaccine comprises a biodegradable nanocomplex with electric properties holding a dengue viral protein inside. An organism has antibody responses after vaccination with the biodegradable nanocomplex twice. Accordingly, in comparison with the Alum adjuvant and Ribi adjuvant used in the traditional dengue vaccine of the prior art, the vaccination times in the present invention is decreased to further reduce the vaccination cost, so the biodegradable high-efficiency dengue vaccine is good for being a commercial vaccine.

## Claims

### Claim 1

A biodegradable high-efficiency dengue vaccine, comprising:
a biodegradable nanocomplex with an electric property holding a dengue viral protein inside, wherein an organism has an antibody response after vaccination with the biodegradable nanocomplex twice.

### Claim 2 (depends on 1)

The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the dose of the biodegradable nanocomplex is no more than 25 μg for a first vaccination.

### Claim 3 (depends on 1)

The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the organism has an antibody titer of 32000 at least after a second vaccination with the biodegradable nanocomplex.

### Claim 4 (depends on 3)

The biodegradable high-efficiency dengue vaccine as claimed in claim 3, wherein the organism has the antibody titer of 1:256000 after the second vaccination with the biodegradable nanocomplex.

### Claim 5 (depends on 1)

The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the dengue viral protein comprising:
a nonstructural chimeric protein DJ NS1, comprising:
a N-terminal amino acid 1-270 of a dengue virus nonstructural protein (DV NS1); and
a C-terminal amino acid 271-352 of a Japanese encephalitis virus nonstructural protein (JEV NS1).

### Claim 6 (depends on 5)

The biodegradable high-efficiency dengue vaccine as claimed in claim 5, wherein the sequence similarity between the nonstructural chimeric protein DJ NS1 and the SEQ. ID. NO.1 is more than 90%.

### Claim 7 (depends on 1)

The biodegradable high-efficiency dengue vaccine as claimed in claim 1, wherein the biodegradable nanocomplex is made from a chitosan with positive charge and a heparin or polyglutamic acid with negative charge.

### Claim 8

A method for making a biodegradable high-efficiency dengue vaccine, comprising the steps of:
preparing a first solution comprising a first biodegradable macromolecule with a first electric property;
dissolving a dengue viral protein with the same electric property as the first biodegradable macromolecule into the first solution to be a mixture solution with the first electric property;
preparing a second solution comprising a second biodegradable macromolecule with a second electric property, wherein the first electric property is opposite to the second electric property; and
adding the mixture solution into the second solution for forming a biodegradable nanocomplex by attraction force between the different electric properties, wherein the dengue viral protein is held in the biodegradable nanocomplex.

### Claim 9 (depends on 8)

The making method as claimed in claim 8, wherein the first macromolecule is heparin or polyglutamic acid, and the first electric property is a negative charge.

### Claim 10 (depends on 8)

The making method as claimed in claim 8, wherein the second macromolecule is chitosan or collagen, and the second electric property is a positive charge.

### Claim 11 (depends on 8)

The making method as claimed in claim 8, wherein the dengue viral protein comprising:
a nonstructural chimeric protein DJ NS1, comprising:
a N-terminal amino acid 1-270 of a dengue virus nonstructural protein (DV NS 1); and
a C-terminal amino acid 271-352 of a Japanese encephalitis virus nonstructural protein (JEV NS1).

### Claim 12 (depends on 11)

The making method as claimed in claim 11, wherein the sequence similarity between the nonstructural chimeric protein DJ NS1 and the SEQ. ID. NO.1 is more than 90%.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising:
a biodegradable high-efficiency dengue vaccine as claimed in claim 1 or an addition salt thereof with a pharmaceutically acceptable base; and
at least one pharmaceutically acceptable excipient.

### Claim 14 (depends on 13)

The pharmaceutical composition as claimed in claim 13. which is used for producing a vaccine or a drug for treating or preventing hemorrhagic dengue fever or dengue shock syndrome.