# US 12,214,014 B2 · Methods for scar reduction by converting scar fibroblasts into adipocytes with hair follicle-derived signals

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- Number: US 12,214,014 B2
- Document ID: US12214014B2
- Status: Granted
- Kind: B2
- Application number: 16/475,570
- Filed: 2018-01-03
- Published: 2020-04-23
- Granted: 2025-02-04
- Earliest claimed: 2017-01-04
- Assignees: The Trustees of the University of Pennsylvania; The Regents of the University of California
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: George Cotsarelis; Christian F. Guerrero-Juarez; Maksim Plikus
- Web page: https://patentgrep.com/patent/US12214014B2

## CPC

- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors}
- A61K 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- C12N 5/0625: {Epidermal cells, skin cells; Cells of the oral mucosa}
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2506/1307: from adult fibroblasts
- 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

This invention describes methods for treating wound healing pathologies, inhibiting or reversing fibrotic skin disorders, including but not limited to keloids, atrophic and hypertrophic scars, and reversing skin aging via generating new dermal adipocytes (DAs). Methods described herein comprise (a) grafting of human hair follicles or (b) direct delivery of conditioned media from in vitro cultured hair follicles, or (c) delivery of purified individual factors secreted by hair follicles, or (d) delivery of small molecule agonists that mimic hair derived signaling activities, or (e) delivery of small molecule antagonists that inhibit anti-adipogenic programs, or (f) delivery of small molecule agonists of pro-adipogenic programs to convert endogenous wound or scar skin fibroblasts into new DAs.

## Claims

### Claim 1

A method for treating wound healing pathologies or for inhibiting or suppressing a fibrotic skin disorder in a subject having a wound healing pathology or fibrotic skin disorder, the method comprising the step of administering to the subject a composition consisting of therapeutically effective amount of a wild-type bone morphogenetic protein 2 (BMP2) polypeptide, or a wild-type bone morphogenetic protein 4 (BMP4) polypeptide, or a combination thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein said wound healing pathology or said fibrotic skin disorder is atrophic scars (AS), hypertrophic scars (HS), keloid scars (KS), or another condition characterized by abnormal proliferation of mesenchymal scar tissue.

### Claim 3 (depends on 2)

The method of claim 2, wherein said step of administering is performed during spreading stage of scar formation.

### Claim 4 (depends on 1)

The method of claim 1, wherein said step of administering is via topical administration.

### Claim 5 (depends on 1)

The method of claim 1, wherein said step of administering is via intradermal or subepidermal administration.

### Claim 6 (depends on 1)

The method of claim 1, further comprising the step of administering a corticosteroid to the subject.

### Claim 7 (depends on 6)

The method of claim 6, wherein the corticosteroid is administered by intralesional injection.

### Claim 8 (depends on 1)

The method of claim 1, wherein the composition comprises a human wild-type bone morphogenic protein 4 (hBMP4).

### Claim 9 (depends on 1)

The method of claim 1, wherein the composition is in aqueous solution or suspension at from about 6 ng/ml to about 25 ng/mL.

### Claim 10 (depends on 8)

The method of claim 8, wherein the composition is in aqueous solution or suspension at from about 6 ng/ml to about 25 ng/mL.