# US 2014/0155343 A1 · Targeted delivery of drugs, therapeutic nucleic acids and functional nucleic acids to mammalian cells via intact killed bacterial cells

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- Number: US 2014/0155343 A1
- Document ID: US20140155343A1
- Status: Published application
- Kind: A1
- Application number: 14/088,067
- Filed: 2013-11-22
- Published: 2014-06-05
- Earliest claimed: 2006-06-23
- Assignees: EnGeneIC Molecular Delivery Pty Ltd
- Applicants: Engeneic Molecular Delivery Pty Ltd
- Inventors: HIMANSHU BRAHMBHATT; JENNIFER MACDIARMID
- Web page: https://patentgrep.com/patent/US20140155343A1

## CPC

- A61K 47/46: Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- 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 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61K 48/0008: {characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/1203: Gram-negative bacteria
- C07K 16/1235: Salmonella (G)
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/505: {comprising antibodies}
- C07K 2317/31: multispecific
- 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
- 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

A composition comprising intact killed bacterial cells that contain a therapeutic nucleic acid, a drug or a functional nucleic acid is useful for targeted delivery to mammalian cells. The targeted delivery optionally employs bispecific ligands, comprising a first arm that carries specificity for a killed bacterial cell surface structure and a second arm that carries specificity for a mammalian cell surface receptor, to target killed bacterial cells to specific mammalian cells and to cause endocytosis of the killed bacterial cells by the mammalian cells. Alternatively, the delivery method exploits the natural ability of phagocytic mammalian cells to engulf killed bacterial cells without the use of bispecific ligands.

## Claims

### Claim 1

A delivery method that comprises bringing a composition comprising (a) a plurality of intact killed bacterial cells that contain an agent selected from the group consisting of a functional nucleic acid, a therapeutic nucleic acid and a drug and (b) a ligand that carries specificity for a non-phagocytic mammalian cell surface receptor that activates receptor-mediated endocytosis into contact with endocytosis-competent mammalian cells, such that said intact killed bacterial cells are endocytosed by said mammalian cells via receptor-mediated endocytosis, thereby delivering said agent to said mammalian cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein said plurality contains a therapeutically significant concentration of said agent.

### Claim 3 (depends on 1)

The method of claim 1, wherein said contact is in vivo.

### Claim 4 (depends on 1)

The method of claim 1, wherein said contact is in vitro.

### Claim 5 (depends on 1)

The method of claim 1, wherein said agent is a functional nucleic acid.

### Claim 6 (depends on 5)

The method of claim 5, wherein said plurality contains a therapeutically significant concentration of said functional nucleic acid and there is an absence from said intact killed bacterial cells of a construct for in situ expression of said functional nucleic acid.

### Claim 7 (depends on 5)

The method of claim 5, wherein said composition further comprises a drug.

### Claim 8 (depends on 7)

The method of claim 7, wherein said functional nucleic acid targets the transcript of a protein that contributes to resistance to said drug.

### Claim 9 (depends on 8)

The method of claim 8, wherein said drug is packaged in a killed cell.

### Claim 10 (depends on 1)

The method of claim 1, wherein said agent is a therapeutic nucleic acid.

### Claim 11 (depends on 10)

The method of claim 10, wherein said therapeutic nucleic acid is encoded by a plasmid.

### Claim 12 (depends on 11)

The method of claim 11, wherein said plasmid is released from said intact killed bacterial cells into said mammalian cells and expressed in said mammalian cells.

### Claim 13 (depends on 10)

The method of claim 10, wherein said therapeutic nucleic acid encodes a suicide gene.

### Claim 14 (depends on 1)

The method of claim 1, wherein said agent is a drug.

### Claim 15 (depends on 14)

The method of claim 14, wherein said drug is a small molecule drug.

### Claim 16 (depends on 14)

The method of claim 14, wherein said drug is a cancer chemotherapeutic agent.