# US 2020/0399603 A1 · Brown fat cells and method for preparing same

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- Number: US 2020/0399603 A1
- Document ID: US20200399603A1
- Status: Published application
- Kind: A1
- Application number: 17/010,778
- Filed: 2020-09-02
- Published: 2020-12-24
- Earliest claimed: 2012-07-12
- Assignees: Kyoto Prefectural Public University Corporation
- Applicants: Kyoto Prefectural Public University Corporation
- Inventors: Tsunao Kishida; Osam Mazda
- Web page: https://patentgrep.com/patent/US20200399603A1

## CPC

- C12N 5/0653: {Adipocytes; Adipose tissue}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- C12N 2501/01: Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
- 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 2501/39: Steroid hormones
- C12N 2501/395: Thyroid hormones
- C12N 2501/60: Transcription factors
- C12N 2501/606: c-Myc
- C12N 2506/09: from epidermal cells, from skin cells, from oral mucosa cells
- C12N 2506/13: from connective tissue cells, from mesenchymal cells
- C12N 2506/1307: from adult fibroblasts
- C12N 2506/45: from artificially induced pluripotent stem 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention provides a method for preparing a brown adipocyte from a somatic cell of a mammal by introducing at least one brown adipocyte-related gene or expression product thereof and at least one reprogramming-related gene or expression product thereof into the somatic cell, the brown adipocyte-related gene being at least one member selected from the group consisting of PRDM16(P) and C/EBPβ(C), the reprogramming-related gene being at least one member selected from the group consisting of Myc family genes (c-Myc(M), N-Myc, L-Myc(L), S-Myc, and B-Myc), GLIS family genes (GLIS1 (G), GLIS 2, and GLIS 3), Klf family genes (KLF1, KLF2, KLF3, KLF4(K), KLF5, KLF6, KLF7, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14, KLF15, KLF16, and KLF17), Oct family genes, Sox family genes, and Lin-28.

## Claims

### Claim 1

A method for generating a brown adipocyte from a somatic cell in a mammal, the method comprising introducing a polynucleotide encoding at least one brown adipocyte-related gene and a polynucleotide encoding at least one reprogramming-related gene into the somatic cell in the mammal, thereby expressing a brown adipocyte-related gene and a reprogramming-related gene in the somatic cell,
wherein
a combination of the at least one brown adipocyte-related gene and the at least one reprogramming-related gene is any combination selected from the group consisting of CM, PCLMG, CLMG, PCIM, CLM, PCMG, PCM, CL, and CMG, wherein P represents PRDM16, C represents C/EBP3, L represents L-Myc, M represents c-Myc, N represents N-Myc, and G represents Glis1,
the polynucleotide encoding at least one brown adipocyte-related gene and the polynucleotide encoding at least one reprogramming-related gene are introduced into the somatic cell by infection with a viral vector, by transfection with a plasmid vector, or by transfection with an episomal vector,
the brown adipocyte is directly induced from the somatic cell without first becoming an induced pluripotent stem (iPS) cell or an embryonic stem (ES) cell, and
the somatic cell is a fibroblast or a white adipocyte.

### Claim 2 (depends on 1)

The method of claim 1, wherein the mammal is a human.

### Claim 3 (depends on 1)

The method of claim 1, wherein the combination of the at least one brown adipocyte-related gene and the at least one reprogramming-related gene is any combination selected from the group consisting of CM, PCLMG, CLMG, PCLM, CIM, PCMG, PCM, and CMG.

### Claim 4 (depends on 3)

The method of claim 3, wherein the mammal is a human.

### Claim 5

A method for generating a brown adipocyte from a somatic cell in a mammal, the method comprising introducing a polynucleotide encoding at least one brown adipocyte-related gene and a polynucleotide encoding at least one reprogramming-related gene into the somatic cell in the mammal, thereby expressing a brown adipocyte-related gene and a reprogramming-related gene in the somatic cell,
wherein
the at least one brown adipocyte related gene is selected from PRDM16 and C/EBPβ and the at least one reprogramming-related gene is selected from c-Myc, N-Myc, L-Myc, and Glis1,
the polynucleotide encoding at least one brown adipocyte-related gene and the polynucleotide encoding at least one reprogramming-related gene are introduced into the somatic cell by infection with a viral vector, transfection with a plasmid vector, or by transfection of an episomal vector, herein the brown adipocyte is directly induced from the somatic cell without first becoming an induced pluripotent stem (iPS) cell or an embryonic stem (ES) cell, and
the somatic cell is a fibroblast or a white adipocyte.

### Claim 6 (depends on 5)

The method of claim 5, wherein the mammal is a human.

### Claim 7 (depends on 1)

A method for the treatment of obesity, diabetes, impaired glucose tolerance, abnormal lipid metabolism, arteriosclerotic disease, hypertension, hyperuricemia, gout, non-alcoholic fatty liver disease, or metabolic syndrome in a patient, the method comprising administering to the patient a brown adipocyte prepared by the method of claim 1, thereby treating the patient.

### Claim 8 (depends on 7)

The method of claim 7, wherein the mammal is a human.

### Claim 9 (depends on 3)

A method for the treatment of obesity, diabetes, impaired glucose tolerance, abnormal lipid metabolism, arteriosclerotic disease, hypertension, hyperuricemia, gout, non-alcoholic fatty liver disease, or metabolic syndrome in a patient, the method comprising administering to the patient a brown adipocyte prepared by the method of claim 3, thereby treating the patient.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mammal is a human.

### Claim 11 (depends on 5)

A method for the treatment of obesity, diabetes, impaired glucose tolerance, abnormal lipid metabolism, arteriosclerotic disease, hypertension, hyperuricemia, gout, non-alcoholic fatty liver disease, or metabolic syndrome in a patient, the method comprising administering to the patient a brown adipocyte prepared by the method of claim 5, thereby treating the patient.

### Claim 12 (depends on 11)

The method of claim 11, wherein the mammal is a human.

### Claim 13 (depends on 1)

A grafting material comprising a brown adipocyte prepared by the method of claim 1.

### Claim 14 (depends on 3)

A grafting material comprising a brown adipocyte prepared by the method of claim 3.

### Claim 15 (depends on 5)

A grafting material comprising a brown adipocyte prepared by the method of claim 5.