# US 11,896,622 B2 · Methods of producing pancreatic hormones

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- Number: US 11,896,622 B2
- Document ID: US11896622B2
- Status: Granted
- Kind: B2
- Application number: 16/679,100
- Filed: 2019-11-08
- Published: 2020-10-08
- Granted: 2024-02-13
- Earliest claimed: 2006-03-02
- Assignees: ViaCyte, Inc.
- Applicants: ViaCyte, Inc.
- Inventors: Laura Martinson; Evert Kroon; Kevin D'Amour; Emmanuel Edward Baetge
- Web page: https://patentgrep.com/patent/US11896622B2

## CPC

- A61K 35/39: Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36)
- A61K 38/26: Glucagons
- A61K 38/28: Insulins
- C12N 5/0676: {Pancreatic cells}
- C12N 5/0678: {Stem cells; Progenitor cells; Precursor cells}
- 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)
- C12N 2500/38: Vitamins
- C12N 2501/10: Growth factors
- C12N 2501/105: Insulin-like growth factors [IGF]
- C12N 2501/113: Acidic fibroblast growth factor (aFGF, FGF-1)
- 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 2501/12: Hepatocyte growth factor [HGF]
- C12N 2501/16: Activin; Inhibin; Mullerian inhibiting substance
- C12N 2501/33: Insulin
- C12N 2501/385: of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
- C12N 2501/41: Hedgehog proteins; Cyclopamine (inhibitor)
- C12N 2501/415: Wnt; Frizzeled
- C12N 2501/42: Notch; Delta; Jagged; Serrate
- C12N 2501/58: Adhesion molecules, e.g. ICAM, VCAM, CD18 (ligand), CD11 (ligand), CD49 (ligand)
- C12N 2501/999: Small molecules not provided for elsewhere
- C12N 2506/02: from embryonic cells
- 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)
- 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 methods of producing pancreatic hormone-expressing cells by first differentiating pluripotent cells in cell culture so as to produce endodermal cells, the endodermal cells being competent to further differentiate into hormone-expressing cells capable of secreting at least one pancreatic hormone in response to a physiological signal, and then, transplanting the cultured endodermal cells into an organism, such as an organism in need of an endocrine cell therapy.

## Claims

### Claim 1

A method for producing insulin in a human subject in need thereof, comprising: maturing in vivo a cell population comprising human PDX-1 positive pancreatic cells that has been transplanted into the human subject,
thereby obtaining insulin secreting cells that secrete insulin in response to glucose stimulation, and producing insulin in the human subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the human PDX-1 positive pancreatic cells also express NKX6.1.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cell culture also comprises human endocrine precursor cells that express neurogenin 3 (NEUROG3).

### Claim 4 (depends on 1)

The method of claim 1, wherein the human PDX-1 positive pancreatic cells are pancreatic endoderm cells, pancreatic progenitor cells, endocrine precursor cells, endocrine progenitor cells, immature pancreatic islet hormone expressing cells, or mature pancreatic islet hormone expressing cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the human subject has been identified as having a condition which limits the ability of the human subject to produce sufficient levels of insulin in response to physiologically high blood glucose concentrations.

### Claim 6 (depends on 1)

The method of claim 1, wherein insulin secretion is detected by measuring C-peptide levels in a sample obtained from the human subject.

### Claim 7 (depends on 6)

The method of claim 6, wherein C-peptide levels increase over time.

### Claim 8 (depends on 1)

The method of claim 1, wherein the insulin secreting cells are responsive to blood glucose.

### Claim 9 (depends on 1)

The method of claim 1, wherein the insulin secreting cells increase in number over time.

### Claim 10 (depends on 1)

The method of claim 1, wherein the insulin secreting cells form islet like cell clusters.

### Claim 11 (depends on 1)

The method of claim 1, wherein the human PDX-1 positive pancreatic cells form pancreatic epithelium in the human subject.

### Claim 12 (depends on 11)

The method of claim 11, wherein the pancreatic epithelium expresses NKX6.1.

### Claim 13 (depends on 11)

The method of claim 11, wherein the pancreatic epithelium expands over time.

### Claim 14

A method for producing insulin in a human in need thereof, said method comprising the steps of:
a) transplanting a cell population comprising a population of human PDX-1 positive pancreatic cells into the human; and
b) maturing in vivo the transplanted human PDX-1 positive pancreatic cells of step a) in the human,
thereby obtaining insulin secreting cells that secrete insulin in response to glucose stimulation and producing insulin in the human.