# US 11,026,979 B2 · Human hepatocytes and uses thereof

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- Number: US 11,026,979 B2
- Document ID: US11026979B2
- Status: Granted
- Kind: B2
- Application number: 16/937,777
- Filed: 2020-07-24
- Published: 2020-11-05
- Granted: 2021-06-08
- Earliest claimed: 2014-11-26
- Assignees: Accelerated Biosciences Corp.
- Applicants: Accelerated Biosciences Corp.
- Inventors: Jau-Nan Lee; Tony Tung-Yin Lee; Yuta Lee; Eing-Mei Tsai
- Web page: https://patentgrep.com/patent/US11026979B2

## CPC

- A61K 35/407: Liver; Hepatocytes
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 35/00: Antineoplastic agents
- C12N 5/067: {Hepatocytes}
- C12N 5/0671: {Three-dimensional culture, tissue culture or organ culture; Encapsulated cells}
- A61K 35/545: Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
- C12N 2501/115: Basic fibroblast growth factor (bFGF, FGF-2)
- C12N 2501/12: Hepatocyte growth factor [HGF]
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/20: Cytokines; Chemokines
- C12N 2501/237: Oncostatin M [OSM]
- C12N 2501/39: Steroid hormones
- C12N 2501/40: Regulators of development
- C12N 2501/65: MicroRNA
- C12N 2506/025: from extra-embryonic cells, e.g. trophoblast, placenta
- 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

Disclosed herein are human hepatocytes for example isolated human hepatic progenitor cells, artificial tissue or organ thereof, and kits or compositions thereof. Also disclosed herein are various methods of using a human hepatocyte disclosed herein.

## Claims

### Claim 1

An isolated human hepatocyte, wherein the isolated human hepatocyte endogenously expresses transforming growth factor beta 1 (TGFβ1), fibronectin, and collagen IV.

### Claim 2 (depends on 1)

The isolated human hepatocyte of claim 1, wherein the isolated human hepatocyte is a human hepatic progenitor cell.

### Claim 3 (depends on 1)

The isolated human hepatocyte of claim 1, wherein the isolated human hepatocyte further expresses human leukocyte antigen G (HLA-G).

### Claim 4 (depends on 1)

The isolated human hepatocyte of claim 1, wherein the isolated human hepatocyte recruits CD4+Foxp3+Treg cells.

### Claim 5 (depends on 1)

The isolated human hepatocyte of claim 1, wherein a plurality of the isolated human hepatocytes forms a tissue of a 3-dimensional structure.

### Claim 6 (depends on 1)

The isolated human hepatocyte of claim 1, wherein a plurality of the isolated human hepatocytes forms a crescent cell mass.

### Claim 7 (depends on 1)

A population of isolated human hepatocytes that comprises a plurality of the isolated human hepatocytes of claim 1, wherein the plurality of isolated human hepatocytes are present in a cluster or an aggregate.

### Claim 8 (depends on 1)

A kit that comprises the isolated human hepatocyte of claim 1 and a carrier.

### Claim 9 (depends on 1)

A pharmaceutical composition that comprises the isolated human hepatocyte of claim 1 and a pharmaceutically acceptable carrier.

### Claim 10 (depends on 9)

A method of treating a disorder of liver tissue or liver function in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of claim 9, whereby the disorder is treated.

### Claim 11 (depends on 1)

A method of screening a therapeutic compound for use in treatment or prevention of a condition, comprising:
a) contacting the isolated human hepatocyte of claim 1, with the therapeutic compound; and
b) detecting an expression level of a biomarker in the isolated human hepatocyte.

### Claim 12 (depends on 1)

A method of producing a therapeutic protein, comprising culturing the isolated human hepatocyte of claim 1 in a medium and extracting the therapeutic protein from the medium.

### Claim 13 (depends on 1)

A method of regenerating a liver, comprising applying the isolated human hepatocyte of claim 1 to an ex vivo perfusion system to regenerate the liver.

### Claim 14 (depends on 1)

A cell therapy, comprising intravenously administering to a subject in need thereof a composition that comprises the isolated human hepatocyte of claim 1.

### Claim 15 (depends on 1)

A method of bioprinting, comprising applying the isolated human hepatocyte of claim 1 to a bioprinting system.

### Claim 16 (depends on 1)

A method of generating a tissue scaffold, comprising culturing the isolated human hepatocyte of claim 1 in a medium on a three-dimensional biocompatible substrate to generate the tissue scaffold.

### Claim 17

An artificial tissue or organ, comprising human hepatocytes that endogenously express human leukocyte antigen G (HLA-G) and one or more biomarkers selected from the group consisting of C—X—C chemokine receptor type 4 (CXCR4), forkhead box protein A2 (FOXA2), hematopoietically expressed homeobox (HHEX), cytochrome P450 7A1 (CYP7A1), bile salt export pump (BSEP), alpha-1-antitrypsin member 1 (SERPINA1), ATP-binding cassette sub-family C member 2 (ABCC2), CCAAT-enhancer-binding protein beta (C/EBPβ), hepatocyte nuclear factor 1-alpha (HNF1α), and any combination thereof.