# US 9,005,962 B2 · Regionalised endoderm cells and uses thereof

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- Number: US 9,005,962 B2
- Document ID: US9005962B2
- Status: Granted
- Kind: B2
- Application number: 12/674,890
- Filed: 2008-08-25
- Published: 2012-04-26
- Granted: 2015-04-14
- Earliest claimed: 2007-08-24
- Assignees: The University Court of the University of Edinburgh
- Applicants: Gillian Mary Morrison; Joshua Mark Brickman; Ifigenia Oikonomopoulou
- Inventors: Gillian Mary Morrison; Joshua Mark Brickman; Ifigenia Oikonomopoulou
- Web page: https://patentgrep.com/patent/US9005962B2

## CPC

- C12N 5/0603: {Embryonic cells (production of embryos, nuclear transfer A01K67/027); Embryoid bodies}
- A61K 35/54: Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 11/00: Drugs for disorders of the respiratory system
- C12Q 1/6881: for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
- C12N 2500/90: Serum-free medium, which may still contain naturally-sourced components
- C12N 2501/11: Epidermal growth factor [EGF]
- C12N 2501/115: Basic fibroblast growth factor (bFGF, FGF-2)
- C12N 2501/119: Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/16: Activin; Inhibin; Mullerian inhibiting substance
- C12N 2501/165: Vascular endothelial growth factor [VEGF]
- C12N 2501/385: of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
- C12N 2501/40: Regulators of development
- C12N 2501/41: Hedgehog proteins; Cyclopamine (inhibitor)
- C12N 2501/999: Small molecules not provided for elsewhere
- C12N 2502/02: embryonic cells
- C12N 2506/02: from embryonic cells
- C12N 2510/00: Genetically modified cells
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention relates to the generation of anterior definitive endoderm (ADE) cells from embryonic stem cells and the differentiation of such cells to, for example, pancreatic or liver cells. The invention also relates to cell lines, cell culture methods, cells markers and the like and their potential uses in a variety of applications.

## Claims

### Claim 1

A substantially pure cell population of isolated anterior definitive endoderm (ADE) cells derived from embryonic stem (ES) cells cultured with activin,
wherein the ADE cells are capable of
i) proliferating in an in vitro culture without further differentiation for at least 8 passages and/or over 2 months; and
ii) maintaining the potential to differentiate into derivatives of ADE cells;
wherein the substantially pure cell population comprises at least 40% ADE cells; and
wherein said ADE cells are derived from human or mouse ES cells.

### Claim 2 (depends on 1)

The cell population according to claim 1, wherein said derivatives of ADE cells consist of liver, pancreas, lung, thymus, thyroid, and parathyroid cells.

### Claim 3 (depends on 1)

The cell population according to claim 1, wherein the ADE cells are derived from human ES cells.

### Claim 4 (depends on 1)

The cell population according to claim 1, wherein the ADE cells are derived from mouse ES cells.

### Claim 5 (depends on 1)

The cell population according to claim 1, wherein the ES cells from which the ADE cells are derived are either wild-type or genetically modified ES cells.

### Claim 6 (depends on 1)

The cell population according to claim 1, wherein said derivatives of ADE cells comprise pancreas cells.