# US 11,028,135 B2 · Lactobacillus acidophilus surface layer protein a (SlpA) as a therapeutic agent for the treatment of inflammatory diseases

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- Number: US 11,028,135 B2
- Document ID: US11028135B2
- Status: Granted
- Kind: B2
- Application number: 16/804,020
- Filed: 2020-02-28
- Published: 2020-07-02
- Granted: 2021-06-08
- Earliest claimed: 2014-10-24
- Assignees: University of Florida Research Foundation, Inc.
- Applicants: University of Florida Research Foundation, Incorporated
- Inventors: Yaima L. Lightfoot; Bikash Sahay; Mansour Mohamadzadeh
- Web page: https://patentgrep.com/patent/US11028135B2

## CPC

- C07K 14/335: from Lactobacillus (G)
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 35/747: Lactobacilli, e.g. L. acidophilus or L. brevis
- A61K 38/13: Cyclosporins
- A61K 38/164: {from bacteria}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- C12N 1/20: Bacteria; Culture media therefor
- C12N 15/746: {for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus)}
- 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)
- 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)

## Abstract

The current invention provides a recombinant bacterium, the recombinant bacterium being genetically modified to decrease or eliminate the display of lipoteichoic acid (LTA), surface layer protein B (SlpB) and surface layer protein X (SlpX) on the surface of said bacterium. Efficacious therapies for a subject suffering from an inflammation mediated disease are also provided. The methods of the current invention comprise administering to a subject in need thereof a therapeutically effective amount of the recombinant L. acidophilus cells or a therapeutically effective amount of the isolated surface layer protein A (SlpA) or a non-naturally occurring derivative thereof. The recombinant L. acidophilus cells or SlpA isolated from L. acidophilus can be in a pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or excipient. In an embodiment of the invention, the pharmaceutical composition is administered orally.

## Claims

### Claim 1

A recombinant lactic acid bacterium that is genetically modified to express a polypeptide comprising SEQ ID NO: 4 or a polypeptide that is at least 95% identical to SEQ ID NO: 4 and does not express (i) a polypeptide comprising SEQ ID NO: 1 or orthologs thereof or a polypeptide having at least 95% sequence identity to SEQ ID NO: 1; (ii) a polypeptide comprising SEQ ID NO: 2 or orthologs thereof or a polypeptide having at least 95% sequence identity to SEQ ID NO: 2; and (iii) a polypeptide comprising SEQ ID NO: 3 or orthologs thereof or a polypeptide having at least 95% sequence identity to SEQ ID NO: 3.

### Claim 2 (depends on 1)

The recombinant lactic acid bacterium according to claim 1, wherein said recombinant bacterium is a Lactobacillus strain.

### Claim 3 (depends on 2)

The recombinant lactic acid bacterium according to claim 2, wherein the Lactobacillus strain is L. lactis.

### Claim 4 (depends on 1)

The recombinant lactic acid bacterium according to claim 1, wherein said bacterium lacks genes encoding SEQ ID NO: 1 or orthologues thereof, SEQ ID NO: 2 or orthologues thereof, and SEQ ID NO: 3 or orthologues thereof.

### Claim 5 (depends on 1)

The recombinant lactic acid bacterium according to claim 1, wherein said bacterium does not express (i) a polypeptide having at least 95% sequence identity to SEQ ID NO: 1; (ii) a polypeptide having at least 95% sequence identity to SEQ ID NO: 2; and (iii) a polypeptide having at least 95% sequence identity to SEQ ID NO: 3.

### Claim 6 (depends on 1)

A probiotic food comprising the recombinant lactic acid bacterium of claim 1.