# US 10,869,900 B2 · Composition and products comprising senescent cells for use in tissue regeneration

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- Number: US 10,869,900 B2
- Document ID: US10869900B2
- Status: Granted
- Kind: B2
- Application number: 15/752,765
- Filed: 2016-08-11
- Published: 2018-12-20
- Granted: 2020-12-22
- Earliest claimed: 2015-08-21
- Assignees: QRSkin GmbH
- Applicants: QRSkin GmbH
- Inventors: Martin Funk
- Web page: https://patentgrep.com/patent/US10869900B2

## CPC

- A61K 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39)
- 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)
- A61L 15/40: containing ingredients of undetermined constitution or reaction products thereof {, e.g. plant or animal extracts}
- A61L 26/0057: {Ingredients of undetermined constitution or reaction products thereof}
- A61P 17/00: Drugs for dermatological disorders
- A61L 26/0033: {Collagen}
- A61L 26/0047: {Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042}
- A61L 26/0076: {Sprayable compositions}
- A61L 26/008: {Hydrogels or hydrocolloids}
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to in vitro cultured senescent cells, such as epithelial cells, keratinocytes and/or fibroblasts as well as their use in the treatment of tissue regeneration, particularly for the treatment of wounds such as burns or ulcers or the treatment of inflammatory conditions. Optionally, products may be used in combination with further drugs including antimicrobial or antidiabetic agents.

## Claims

### Claim 1

A method for treating a tissue for tissue regeneration, comprising providing a composition comprising a cell component, wherein the cell component includes a senescent cell type or a combination of senescent cell types, and applying said composition to the tissue to be treated, wherein the cell component includes mainly one cell type, the cell type being keratinocytes, and wherein at least 85% of all cells in the composition are keratinocytes.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the senescent cell type derives from cells selected from the group consisting of epithelial cells, corneal epithelial cells, keratinocytes, fibroblasts, melanocytes, endothelial cells, pericytes, monocytes, lymphocytes, thrombocytes, mast cells, adipocytes, muscle cells, neurons, osteocytes, osteoblasts, chondrocytes, mesenchymal stem cells and/or an adult or embryonic stem cells.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the cells are allogeneic, autogeneic or xenogeneic.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the cell component includes more than 70% senescent keratinocytes.

### Claim 5 (depends on 3)

The method according to claim 3, wherein the cell component includes more than 90% senescent keratinocytes.

### Claim 6 (depends on 5)

The method according to claim 5, wherein senescence is induced by cell culture stress, by cell contact inhibition or by administration of surfactants.

### Claim 7 (depends on 1)

The method according to claim 1, wherein senescence is characterized by cell cycle arrest in the presence of growth stimulation and/or wherein senescence is induced by cell cycle arrest in the presence of sustained growth stimulation.

### Claim 8 (depends on 1)

The method according to claim 1, wherein senescent cells express and/or secrete one or more biologically active molecules selected from the group consisting of: IL-1α, IL-1β, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-18, MCP1, MCP2, MCP4, MIF, MIP-1a, MIP-3a, HCC-4, Eotaxin-3, TECK, ENA-78, I-309, I-TAC, GROα, GROβ, GROγ, VEGF, EGF, HGF, FGF, bFGF, KGF, Amphiregulin, Angiogenin, APOJ, CAV1, OSTEO, Epiregulin, Heregulin, SCF, SDF-1 alpha, PIGF, IGFBP-2, -3, -4, -6, -7,GM-CSF, PDGF-BB, TGF-α, TGF-β1, TGF-β2, TGF-β3, ICAM1, ICAM3, TRAIL-R3, Fas, OPG, SGP130, EGF-R uPAR, sTNFRI, sTNFRIII, MMP1, MMP2, MMP3, MMP7, MMP9, MMP10, MMP12, MMP13, MMP14, TIMP1, TIMP2, PAI1, PAI2, Park7DJ-1, uPA/Urokinase, SLPI, Syndecan 1, -4, Tenascin C, Endothelin, Collagens, Fibronectins, Laminins.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the treatment is for treating an acute or chronic wound and/or an inflammatory condition.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the wound is a burn selected from the group consisting of: superficial and/or deep partial thickness burn, second or third degree burn, sun burn, and/or
wherein the wound is a chronic wound-healing disorder selected from the group consisting of ulcers, pressure sores, diabetic foot syndrome.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the cell component includes more than 10% senescent cells.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the cell component includes more than 50% senescent cells.

### Claim 13 (depends on 1)

The method according to claim 1, wherein senescence is induced by cell culture stress selected from the group consisting of: cell overgrowth, cell contact inhibition, high cell density, oxidative stress, presence of reactive oxygen species; administration of surfactants or other small molecule inducers of senescence; senescence-inducing administration of mitomycin C or any other chemically-based mitotic inhibitor; or by irradiation with γ-Rays, irradiation with X-Rays, or irradiation with UV light including UVB; or by treatment with cold plasma, radiation or e-beam treatment.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the senescent cells express and/or secrete at least one or more of IL-8, GROα, VEGF, endothelin, MMP7, MMP9, MMP10, MMP12, MMP13, TIMP1, TIMP2 and TGF-β1.

### Claim 15 (depends on 1)

The method according to claim 1, wherein senescent cells express and/or secrete one or more biologically active molecules selected from the group consisting of: IL-8, GROα, VEGF, endothelin, MMP7, MMP9, MMP10, MMP12, MMP13, TIMP1, TIMP2, TGF-β1 and/or wherein senescent cells are characterized by one or more features selected from the group consisting of: SA β-gal activity, proliferation arrest, p16INK4a expression, DNA-damage signalling, telomere dysfuntion, loss of lamin B1.