# US 8,771,668 B2 · Commensal bacteria as signal mediators within a mammalian host

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- Number: US 8,771,668 B2
- Document ID: US8771668B2
- Status: Granted
- Kind: B2
- Application number: 12/937,176
- Filed: 2009-04-08
- Published: 2011-11-17
- Granted: 2014-07-08
- Earliest claimed: 2008-04-09
- Assignees: Cornell University
- Applicants: John C. March; Franklin Faping Duan
- Inventors: John C. March; Franklin Faping Duan
- Web page: https://patentgrep.com/patent/US8771668B2

## CPC

- C12N 15/74: Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- A23K 10/16: Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions (A23K10/12 takes precedence)
- A23K 10/18: of live microorganisms
- A23K 30/15: using chemicals or microorganisms for ensilaging
- A23K 30/18: using microorganisms or enzymes
- A61K 38/164: {from bacteria}
- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- A61K 38/26: Glucagons
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- C07K 14/4705: {stimulating, promoting or activating activity}
- C07K 14/605: Glucagons
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- C07H 21/04: with deoxyribosyl as saccharide radical
- C12N 15/75: for Bacillus
- C12N 2510/00: Genetically modified cells
- 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)
- A23K: FODDER
- 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)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Genetically engineered cells and microorganisms are provided for preventing or ameliorating diseases through genetically engineered quorum signaling. Therapeutic methods for using the cells and microorganisms to prevent or ameliorate diseases are also provided. The genetically engineered cells or microorganisms can be engineered to express a signal and used to interrupt the signaling-dependent virulence of an invading pathogen. The cells or microorganisms can be used to provide signal-dependent expression of a desirable gene in order to interrupt, prevent, and/or ameliorate a disease of mammals, such as parasitic diseases, infectious diseases, autoimmune diseases and genetic disorders.

## Claims

### Claim 1

A method treating diabetes in a mammalian host comprising:
administering to the gastrointestinal tract of mammalian host a recombinant enteric commensal bacterium comprising a recombinant nucleic acid molecule encoding a signal that comprises a glucagon-like peptide 1 (Glp-1),
wherein the signal is expressed by the recombinant enteric commensal bacterium in the gastrointestinal tract and secreted into the gastrointestinal tract of the mammalian host by the recombinant enteric commensal bacterium in the gastrointestinal tract of the mammalian host, and the signal stimulates expression of insulin by the mammalian host to treat said diabetes.

### Claim 2 (depends on 1)

The method of claim 1 wherein the commensal bacteria comprises a strain of Escherichia coli.

### Claim 3 (depends on 2)

The method of claim 2 wherein the strain of Escherichia coli comprises Escherichia coli Nissle 1917.

### Claim 4 (depends on 1)

The method of claim 1 wherein the diabetes is Type I diabetes.

### Claim 5

A method of treating diabetes in a human, the method comprising:
administering to the gastrointestinal tract of the human a recombinant enteric commensal bacterium that comprises a recombinant nucleic acid molecule that encodes a signal that comprises glucagon-like peptide 1 (Glp-1),
wherein the signal is expressed and secreted by the enteric commensal bacterium in the gastrointestinal tract of the human host, and the signal stimulates production of insulin by the human to treat said diabetes.

### Claim 6 (depends on 5)

The method of claim 5 wherein the commensal bacteria comprises a strain of Escherichia coli.

### Claim 7 (depends on 6)

The method of claim 6 wherein the strain of Escherichia coli comprises Escherichia coli Nissle 1917.

### Claim 8 (depends on 5)

The method of claim 5 wherein the diabetes is Type I diabetes.