# US 9,433,671 B2 · Anti-malaria compositions and methods

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- Number: US 9,433,671 B2
- Document ID: US9433671B2
- Status: Granted
- Kind: B2
- Application number: 13/827,469
- Filed: 2013-03-14
- Published: 2013-10-03
- Granted: 2016-09-06
- Earliest claimed: 2012-03-30
- Assignees: Artificial Cell Technologies, Inc.
- Applicants: Artificial Cell Technologies, Inc.
- Inventors: Thomas J. Powell
- Web page: https://patentgrep.com/patent/US9433671B2

## CPC

- A61K 39/002: Protozoa antigens
- A61K 9/50: Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 39/015: Hemosporidia antigens, e.g. Plasmodium antigens
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/6093: {Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine}
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Multilayer films comprise polypeptide epitopes from Plasmodium falciparum, specifically a circumsporozoite T1, B or T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a Plasmodium protozoan.

## Claims

### Claim 1

A composition comprising
a first multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the polyelectrolyte layers in the multilayer film comprises a first antigenic polypeptide polyelectrolyte,
wherein the first antigenic polypeptide comprises a Plasmodium falciparum circumsporozoite T1BT* epitope covalently linked to one or two surface adsorption regions at the C-terminus and/or the N-terminus of the polypeptide, wherein at least one of the surface adsorption regions comprises eight negatively or positively charged amino acid residues,
wherein the polyelectrolytes in the multilayer film comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule,
wherein the first multilayer film is deposited on a core nanoparticle or microparticle, or is in the form of a nanocapsule or microcapsule prepared by dissolving the core particle,
wherein the first multilayer film retains more than half of its polyelectrolytes when incubated in phosphate buffered saline at 37° C. for 24 hours.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the first multilayer film further comprises a TLR ligand.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the TLR ligand is covalently linked to the first antigenic polypeptide.

### Claim 4 (depends on 1)

The composition of claim 1, further comprising a second multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the layers in the second multilayer film comprises a second antigenic polyelectrolyte,
wherein the second antigenic polyelectrolyte comprises a Plasmodium falciparum circumsporozoite T1, B or T* epitope covalently linked to a second polyelectrolyte, wherein the first and second antigenic polyelectrolytes comprise different Plasmodium falciparum circumsporozoite epitopes.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the first and second polyelectrolytes are polypeptides.

### Claim 6 (depends on 4)

The composition of claim 4, wherein the first and second multilayer films are deposited onto core particles.

### Claim 7 (depends on 4)

The composition of claim 4, wherein the first and/or the second multilayer film further comprises a TLR ligand.

### Claim 8 (depends on 7)

The composition of claim 7, wherein the TLR ligand is covalently linked to the first and/or second antigenic polyelectrolyte.

### Claim 9 (depends on 4)

The composition of claim 4, further comprising a third multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the layers in the third multilayer film comprises a third antigenic polyelectrolyte,
wherein the third antigenic polyelectrolyte comprises a Plasmodium falciparum circumsporozoite T1, B or T* epitope covalently linked to a third polyelectrolyte, wherein the first, second and third antigenic polyelectrolytes comprise different Plasmodium falciparum circumsporozoite epitopes.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the first, second, and third polyelectrolytes are polypeptides.

### Claim 11 (depends on 9)

The composition of claim 9, wherein the first, second, and third multilayer films are deposited onto core particles.

### Claim 12 (depends on 9)

The composition of claim 9, wherein the first, second and/or third multilayer film further comprises a TLR ligand.

### Claim 13 (depends on 12)

The composition of claim 12, wherein the TLR ligand is covalently linked to the first, second and/or third antigenic polyelectrolyte.

### Claim 14 (depends on 1)

A method of eliciting an immune response in a vertebrate organism comprising administering into the vertebrate organism the composition of claim 1.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the multilayer film is covalently crosslinked.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the covalent crosslinks are amide bonds involving amino acid side chain functional groups.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the first antigenic polypeptide has a magnitude of net charge per residue of greater than or equal to 0.2 at pH 7.0.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the composition provides >90% reduction of PfPb (Plasmodium bergheii transfected with the circumsporozoite gene of P. falciparum) parasite rRNA levels in HepG2 cells measured by qPCR in a transgenic sporozoite neutralization assay (TSNA) performed on a 1:5 dilution of serum from C57BL/6J or BALB/c mice immunized on days 0, 21, and 42 with the composition, wherein the serum is harvested on day 49.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the composition produces T1BT*-specific IgG titers, a specific CD4+ T-cell response, or both, in BALB/c or C57BL/6 mice immunized with the compositions.