# US 10,245,288 B2 · Method and system for reducing the likelihood of developing NASH in an individual diagnosed with non-alcoholic fatty liver disease

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- Number: US 10,245,288 B2
- Document ID: US10245288B2
- Status: Granted
- Kind: B2
- Application number: 15/392,173
- Filed: 2016-12-28
- Published: 2017-04-20
- Granted: 2019-04-02
- Earliest claimed: 2011-03-25
- Applicants: Joseph E. Kovarik
- Inventors: Joseph E. Kovarik
- Web page: https://patentgrep.com/patent/US10245288B2

## CPC

- A61K 35/741: Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06)
- A61F 5/0003: {Apparatus for the treatment of obesity; Anti-eating devices (surgical instruments or methods for treatment of obesity, devices specially adapted therefor A61B17/00; hollow or tubular parts of organs A61F2/04)}
- A61K 35/745: Bifidobacteria
- A61K 35/747: Lactobacilli, e.g. L. acidophilus or L. brevis
- 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)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)

## Abstract

A method for reducing the likelihood of developing liver cancer in an individual diagnosed with non-alcoholic fatty liver disease that involves providing an individual with an effective amount of a composition of bacteria modified using a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated system (CRISPR-Cas) or Clustered Regularly Interspaced Short Palindromic Repeats from Prevotella and Francisella 1 (CRISPR/Cpf1) system so that the bacteria is able to produce a therapeutically effective amount of anti-bodies to oxidized low density lipoprotein, with the modified bacteria preferably being from the Lactobacillus, Bifidobacterium, and Streptococcus species; and most preferably including L. reuteri bacteria modified using CRISPR-Cas and/or Cpf1 systems so that it is able to survive the conditions in the duodenum and jejunum of the small intestine of a human.

## Claims

### Claim 1

A method for reducing the likelihood of developing non-alcoholic steatohepatitis (NASH) in an individual diagnosed with non-alcoholic fatty liver disease, comprising: providing in the gut of an individual a population of beneficial bacteria selected from the group consisting of Lactobacillus species; administering at least 6 grams per day of fiber to the individual to maintain a therapeutically effective amount of the beneficial bacteria in the gut of the individual; and inhibiting monoacylglycerolacyltransferase-3 (MGAT3) synthesis in the individual to lower triacylglycerol (TAG) production.

### Claim 2 (depends on 1)

The method as set forth in claim 1, wherein the beneficial bacteria are present on a thin film mucosal layered strip, said beneficial bacteria being encapsulated in a frangible enclosure.

### Claim 3 (depends on 1)

The method as set forth in claim 1, further comprising inhibiting expression of diacylglycerolacyltransferase-2 (DGAT-2) in said individual.

### Claim 4 (depends on 1)

The method as set forth in claim 1, further comprising increasing the levels of Roseburia, while reducing the levels of Akkermansia spp. in the individual's gut microbiome.

### Claim 5 (depends on 4)

The method as set forth in claim 4, wherein the population of beneficial bacteria include bacteria that have been modified to increase the level of butyrate.

### Claim 6

A method for reducing the likelihood of developing non-alcoholic steatohepatitis (NASH) in an individual diagnosed with non-alcoholic fatty liver disease, comprising: providing in the gut of an individual a population of beneficial bacteria selected from the group consisting of Lactobacillus species; administering at least 6 grams per day of fiber to the individual to maintain a therapeutically effective amount of the beneficial bacteria in the gut of the individual; and inhibiting expression of diacylglycerolacyltransferase-2 (DGAT-2) in said individual.

### Claim 7 (depends on 6)

The method as set forth in claim 6, further comprising increasing the levels of Roseburia, while reducing the levels of Akkermansia spp. in the individual's gut microbiome.

### Claim 8 (depends on 6)

The method as set forth in claim 6, wherein the beneficial bacteria are present on a thin film mucosal layered strip, said beneficial bacteria being encapsulated in a frangible enclosure.

### Claim 9 (depends on 6)

The method as set forth in claim 6, wherein the population of beneficial bacteria include bacteria that have been modified to increase the level of butyrate.

### Claim 10

A method for reducing the likelihood of developing non-alcoholic steatohepatitis (NASH) in an individual diagnosed with non-alcoholic fatty liver disease, comprising: providing in the gut of an individual a population of beneficial bacteria selected from the group consisting of Lactobacillus species; administering at least 6 grams per day of fiber to the individual to maintain a therapeutically effective amount of the beneficial bacteria in the gut of the individual; and increasing the levels of Roseburia, while reducing the levels of Akkermansia spp. in the individual's gut microbiome.

### Claim 11 (depends on 10)

The method as set forth in claim 10, further comprising inhibiting expression of diacylglycerolacyltransferase-2 (DGAT-2) in said individual.

### Claim 12 (depends on 10)

The method as set forth in claim 10, wherein the beneficial bacteria are present on a thin film mucosal layered strip, said beneficial bacteria being encapsulated in a frangible enclosure.

### Claim 13 (depends on 10)

The method as set forth in claim 10, wherein the population of beneficial bacteria include bacteria that have been modified to increase the level of butyrate.
