# US 10,501,746 B1 · Bacteria carrying bacteriophage and protease inhibitors for the treatment of disorders and methods of treatment

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- Number: US 10,501,746 B1
- Document ID: US10501746B1
- Status: Granted
- Kind: B1
- Application number: 15/456,091
- Filed: 2017-03-10
- Granted: 2019-12-10
- Earliest claimed: 2013-02-14
- Applicants: David Gordon Bermudes
- Inventors: David Gordon Bermudes
- Web page: https://patentgrep.com/patent/US10501746B1

## CPC

- C12N 15/746: {for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus)}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 38/55: Protease inhibitors
- A61K 39/39558: {against tumor tissues, cells, antigens}
- C07K 16/241: {Tumor Necrosis Factors}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention uses co-expression of protease inhibitors and protease sensitive therapeutic agents including phage and phagemids delivering peptides, therapeutic antibodies, DNA and RNA-based therapeutics that results in treating inflammation of a variety of disorders including psoriasis, atopic dermatitis and inflammatory bowel disease. The invention also provides bacteria that inhibit the growth of intestinal parasites such as worms, and deliver siRNA or miRNA that have specific anti-parasitic effects that results in the reduction or elimination of the parasite.

## Claims

### Claim 1

A pharmaceutically acceptable delivery vehicle for a therapeutic agent to treat a eukaryotic disease of a eukaryotic organism, comprising:
a live bacterium; and
a capsid surrounding a first nucleic acid, selected from the group consisting of a phage, a phagemid and a viroid, produced by the live bacterium,
the first nucleic acid comprising a nucleic acid sequence adapted to cause a eukaryotic cell of the eukaryotic organism, after receipt of the first nucleic acid, to produce a corresponding second nucleic acid effective for treating the eukaryotic disease of the eukaryotic organism wherein the corresponding second nucleic acid encodes a heterologous chimeric peptide.

### Claim 2 (depends on 1)

The delivery vehicle according to claim 1, wherein the live bacterium comprises Salmonella and the eukaryotic organism comprises a mammal.

### Claim 3 (depends on 1)

The delivery vehicle according to claim 1, wherein the heterologous chimeric peptide comprises a fusion protein having a signal sequence, and at least one of a targeting peptide and an antibody peptide portion inserted immediately after the signal sequence.

### Claim 4 (depends on 3)

The delivery vehicle according to claim 3, wherein the fusion protein comprises at least one enterococcal bacteriocin.

### Claim 5 (depends on 1)

The delivery vehicle according to claim 1, wherein the second nucleic acid comprises a translation promoter and a polylinker active in the eukaryotic cell.

### Claim 6 (depends on 1)

The delivery vehicle according to claim 1, wherein the live bacterium comprises a gram positive probiotic bacteria, and the capsid surrounding the first nucleic acid comprises a phage.

### Claim 7 (depends on 1)

The delivery vehicle according to claim 1, wherein the live bacterium comprises at least one bacterium selected from the group consisting of Lactococcus and Lactobacillus.

### Claim 8 (depends on 1)

The delivery vehicle according to claim 1, wherein the capsid comprises at least one of a peptide sequence from M13 filamentous phage and a peptide sequence from B5 filamentous phage.

### Claim 9 (depends on 1)

The delivery vehicle according to claim 1, wherein the eukaryotic disease comprises a skin disease, and the pharmaceutically acceptable delivery vehicle is adapted for dermatological application to skin of the eukaryotic organism to treat the skin disease.

### Claim 10 (depends on 1)

The delivery vehicle according to claim 1, wherein the capsid targets at least one of EFG, TGF, EP3, EP4, GPCR, fibronectin and a peptide mimic of keratinocyte growth factor.

### Claim 11 (depends on 1)

The delivery vehicle according to claim 1, wherein the second nucleic acid encodes at least one of an inhibitor of production of pro-inflammatory cytokines, and a promoter for production of anti-inflammatory cytokines.

### Claim 12 (depends on 1)

The delivery vehicle according to claim 1, wherein the second nucleic acid encodes a parasitic worm toxin.
