# US 2024/0165006 A1 · Dermatological compostions and use thereof

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- Number: US 2024/0165006 A1
- Document ID: US20240165006A1
- Status: Published application
- Kind: A1
- Application number: 18/551,350
- Filed: 2022-03-20
- Published: 2024-05-23
- Earliest claimed: 2021-03-21
- Assignees: Bone Sci. Bio Ltd.
- Applicants: Bone Sci. Bio Ltd.
- Inventors: Yaron Rapaport; Noa Harduf; Hanna Rapaport
- Web page: https://patentgrep.com/patent/US20240165006A1

## CPC

- A61K 8/64: Proteins; Peptides; Derivatives or degradation products thereof
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- 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 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/1709: {from mammals}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61L 27/26: Mixtures of macromolecular compounds
- A61L 27/36: containing ingredients of undetermined constitution or reaction products thereof {, e.g. transplant tissue, natural bone, extracellular matrix (isolated natural compounds, e.g. collagen A61L27/24)}
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/52: Hydrogels or hydrocolloids
- A61Q 19/08: Anti-ageing preparations
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2430/04: for mammary reconstruction
- A61L 2430/34: for soft tissue reconstruction
- 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
- 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)
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## Abstract

Dermatological compositions comprising amphiphilic peptides, derivatives or salts thereof are provided. The compositions are particularly useful as dermal fillers and for inducing soft tissue repair and regeneration.

## Claims

### Claim at position 1

1-47. (canceled)

### Claim 48

A dermatological composition comprising at least one amphiphilic peptide comprising alternating hydrophobic/hydrophilic amino acid residues, or a derivative or a salt thereof, wherein the peptide comprises 1-20 pairs of hydrophobic-hydrophilic alternating amino acid residues wherein the hydrophilic amino acid residue is selected from the group consisting of a negatively charged amino acid, a hydroxyl-containing amino acid, and a phosphorylated-hydroxyl-containing amino acid, and wherein said peptide has no more than 10% positively charged amino acid residues, and a dermatologically acceptable carrier, wherein the dermatological composition is a soft tissue filler composition.

### Claim 49 (depends on 48)

The dermatological composition of claim 48, wherein the at least one amphiphilic peptide has 2 to 40 amino acids, or wherein the at least one amphiphilic peptide comprises at least one terminal Pro residue; or wherein the hydrophobic amino acid residue is selected from the group consisting of Phe, Leu, Ile, Val. Trp, and Ala; or wherein the hydrophilic amino acid residue is selected from the group consisting of Glu, Asp, Tyr, Ser, Thr, Ser(PO4), Thr(PO4), and Tyr(PO4).

### Claim 50 (depends on 48)

The dermatological composition of claim 48, wherein the at least one amphiphilic peptide comprises an amino acid sequence according to Formula I:
X-(hydrophobic-hydrophilic)n-B (Formula I) or a salt thereof,
wherein n designates an integer of 1 to 20, hydrophobic designates a hydrophobic amino acid residue, hydrophilic designates a hydrophilic amino acid residue, X designates Pro, Pro-hydrophilic or the peptide's amino terminus, and B designates Pro or the peptide's carboxy terminus; or wherein the at least one amphiphilic peptide comprises an amino acid sequence of any of the following formulae X-(Phe-Glu)n-B, X-(Phe-Asp)n-B, X-(Leu-Glu)n-B, and X-(Leu-Asp)n-B, or a salt thereof; or wherein the at least one amphiphilic peptide comprises at least one modification selected from a modification of the amino terminus X and a modification of the carboxy terminus B.

### Claim 51 (depends on 50)

The dermatological composition of claim 50, wherein the modification comprises acetylation of the amino terminus, amidation of the carboxy terminus, or a combination thereof.

### Claim 52 (depends on 48)

The dermatological composition of claim 48, wherein the at least one amphiphilic peptide comprises a sequence selected from the group consisting of:
(SEQ ID NO: 1)
Pro-(Asp-Phe)5-Asp-Pro,
(SEQ ID NO: 2)
Pro-Glu-(Phe-Glu)5,
(SEQ ID NO: 3)
Glu-(Phe-Glu)5-Pro,
(SEQ ID NO: 4)
Pro-(Ser-Phe)5-Ser-Pro,
(SEQ ID NO: 5)
Pro-(SerPO4-Phe)5-SerPO4-Pro,
(SEQ ID NO: 6)
Pro-(TyrPO4-Phe)5-TyrPO4-Pro,
(SEQ ID NO: 7)
Pro-(Glu-Leu)5-Glu-Pro,
(SEQ ID NO: 8)
Pro-(Asp-Leu)5-Asp-Pro,
(SEQ ID NO: 9)
Pro-(Ser-Leu)5-Ser-Pro,
(SEQ ID NO: 10)
Pro-(SerPO4-Leu)5-SerPO4-Pro,
(SEQ ID NO: 11)
Pro-(TyrPO4-Leu)5-TyrPO4-Pro,
(SEQ ID NO: 12)
Pro-(Glu-Phe-Ser-Phe)4-Glu-Pro,
(SEQ ID NO: 13)
Pro-(SerPO4-Phe-Ser-Phe)4-Ser-Pro,
(SEQ ID NO: 14)
Pro-(SerPO4-Phe-Glu-Phe)4-Glu-Pro,
(SEQ ID NO: 15)
Pro-(SerPO4-Phe-Asp-Phe)4-Asp-Pro,
(SEQ ID NO: 16)
Ala-Leu-Glu-(Phe-Glu)3-Pro-Ala-(Glu-Phe)3-Glu-Leu-
Pro-Ala-Leu-Glu-(Phe-Glu)3-Pro,
(SEQ ID NO: 17)
Pro-Glu-(Phe-Glu)2-Lys-(Glu-Phe)2-Glu-Pro,
(SEQ ID NO: 18)
Pro-Glu-(Phe-Glu)5-(Gly)3-Arg-Gly-Asp-Ser,
(SEQ ID NO: 19)
(Phe-Glu)3-Pro-(Gly)3-Arg-Gly-Asp-Ser,
(SEQ ID NO: 20)
Ac-Pro-Asp-(Phe-Asp)5-Pro-NH2,
(SEQ ID NO: 21)
Pro-Asp-(Phe-Asp)6,
(SEQ ID NO: 22)
(Phe-Asp)6,
(SEQ ID NO: 23)
Pro-Glu-(Phe-Glu)5-Pro,
(SEQ ID NO: 24)
Pro-Asp-(Phe-Asp)5-Pro-NH2,
(SEQ ID NO: 25)
(Phe-Glu)5,
(SEQ ID NO: 26)
(Phe-Glu)6,
(SEQ ID NO: 27)
(Phe-Glu)7,
(SEQ ID NO: 28)
Pro-Asp-(Phe-Asp)4,
(SEQ ID NO: 29)
Pro-Asp-(Phe-Asp)6,
(SEQ ID NO: 30)
Pro-Asp-(Phe-Asp)8,
(SEQ ID NO: 31)
(Phe-Asp)5,
(SEQ ID NO: 32)
(Phe-Asp)6,
(SEQ ID NO: 33)
(Phe-Asp)7,
(SEQ ID NO: 34)
Pro-Asp-(Phe-Asp)5-Pro-Arg-Gly-Asp-Ser,
(SEQ ID NO: 35)
Pro-(Phe-Asp)3-Pro,
and
(SEQ ID NO: 36)
Pro-(Phe-Asp)3-Pro-(Gly)3-Arg-Gly-Asp-Ser,
or a salt thereof.

### Claim 53 (depends on 52)

The dermatological composition of claim 52, wherein the at least one amphiphilic peptide comprises a sequence as set forth in SEQ ID NO: 1, or a salt thereof.

### Claim 54 (depends on 48)

The dermatological composition of claim 48, formulated for intradermal or subcutaneous administration or formulated for use in 3D bioprinting of an artificial tissue.

### Claim 55 (depends on 54)

The dermatological composition of claim 54 in the form of a hydrogel.

### Claim 56 (depends on 48)

The dermatological composition of claim 48, further comprising at least one of hyaluronic acid, collagen, gelatin, elastin, laminin, and fibronectin.

### Claim 57 (depends on 48)

The dermatological composition of claim 48 further comprising a plurality of cells obtained from adipose tissue.

### Claim 58 (depends on 57)

The dermatological composition of claim 57, wherein the plurality of cells obtained from adipose tissue comprise adipocytes and/or adipose-derived stem cells, or wherein the plurality of cells obtained from adipose tissue are autologous; or wherein the plurality of cells obtained from adipose tissue are obtained by lipoaspiration, or wherein the plurality of cells obtained from adipose tissue are allogeneic.

### Claim 59 (depends on 48)

A method of treating a soft tissue defect, the method comprising the step of injecting or implanting to a subject in need thereof an effective amount of the dermatological composition of claim 48.

### Claim 60 (depends on 59)

The method of claim 59, wherein treating a soft tissue defect comprises face or body contouring; or wherein treating a soft tissue defect comprises breast augmentation following mastectomy.

### Claim 61 (depends on 48)

A pre-filled syringe comprising the dermatological composition of claim 48.

### Claim 62

A dermatological composition comprising at least one amphiphilic peptide comprising alternating hydrophobic/hydrophilic amino acid residues, or a derivative or a salt thereof, wherein the peptide comprises 1-20 pairs of hydrophobic-hydrophilic alternating amino acid residues wherein the hydrophilic amino acid residue is selected from the group consisting of a negatively charged amino acid, a hydroxyl-containing amino acid, and a phosphorylated-hydroxyl-containing amino acid, and wherein said peptide has no more than 10% positively charged amino acid residues, and a dermatologically acceptable carrier, wherein the dermatological composition is a cosmetic composition.

### Claim 63 (depends on 62)

The dermatological composition of claim 62, wherein the at least one amphiphilic peptide has 2 to 40 amino acids; or wherein the at least one amphiphilic peptide comprises at least one terminal Pro residue; or wherein the hydrophobic amino acid residue is selected from the group consisting of Phe, Leu, Ile, Val, Trp, and Ala; or wherein the hydrophilic amino acid residue is selected from the group consisting of Glu, Asp, Tyr, Ser, Thr, Ser(PO4), Thr(PO4), and Tyr(PO4); or wherein the at least one amphiphilic peptide comprises an amino acid sequence according to Formula I:
X-(hydrophobic-hydrophilic)n-B (Formula I) or a salt thereof,
wherein n designates an integer of 1 to 20, hydrophobic designates a hydrophobic amino acid residue, hydrophilic designates a hydrophilic amino acid residue, X designates Pro, Pro-hydrophilic or the peptide's amino terminus, and B designates Pro or the peptide's carboxy terminus; or wherein the at least one amphiphilic peptide comprises an amino acid sequence of any of the following formulae X-(Phe-Glu)n-B, X-(Phe-Asp)n-B, X-(Leu-Glu)n-B, and X-(Leu-Asp)n-B, or a salt thereof; or wherein the at least one amphiphilic peptide comprises at least one modification selected from a modification of the amino terminus X and a modification of the carboxy terminus B.

### Claim 64 (depends on 62)

The dermatological composition of claim 62, wherein the at least one amphiphilic peptide comprises a sequence selected from the group consisting of:
(SEQ ID NO: 1)
Pro-(Asp-Phe)5-Asp-Pro,
(SEQ ID NO: 2)
Pro-Glu-(Phe-Glu)5,
(SEQ ID NO: 3)
Glu-(Phe-Glu)5-Pro,
(SEQ ID NO: 4)
Pro-(Ser-Phe)5-Ser-Pro,
(SEQ ID NO: 5)
Pro-(SerPO4-Phe)5-SerPO4-Pro,
(SEQ ID NO: 6)
Pro-(TyrPO4-Phe)5-TyrPO4-Pro,
(SEQ ID NO: 7)
Pro-(Glu-Leu)5-Glu-Pro,
(SEQ ID NO: 8)
Pro-(Asp-Leu)5-Asp-Pro,
(SEQ ID NO: 9)
Pro-(Ser-Leu)5-Ser-Pro,
(SEQ ID NO: 10)
Pro-(SerPO4-Leu)5-SerPO4-Pro,
(SEQ ID NO: 11)
Pro-(TyrPO4-Leu)5-TyrPO4-Pro,
(SEQ ID NO: 12)
Pro-(Glu-Phe-Ser-Phe)4-Glu-Pro,
(SEQ ID NO: 13)
Pro-(SerPO4-Phe-Ser-Phe)4-Ser-Pro,
(SEQ ID NO: 14)
Pro-(SerPO4-Phe-Glu-Phe)4-Glu-Pro,
(SEQ ID NO: 15)
Pro-(SerPO4-Phe-Asp-Phe)4-Asp-Pro,
(SEQ ID NO: 16)
Ala-Leu-Glu-(Phe-Glu)3-Pro-Ala-(Glu-Phe)3-Glu-Leu-
Pro-Ala-Leu-Glu-(Phe-Glu)3-Pro,
(SEQ ID NO: 17)
Pro-Glu-(Phe-Glu)2-Lys-(Glu-Phe)2-Glu-Pro,
(SEQ ID NO: 18)
Pro-Glu-(Phe-Glu)5-(Gly)3-Arg-Gly-Asp-Ser,
(SEQ ID NO: 19)
(Phe-Glu)3-Pro-(Gly)3-Arg-Gly-Asp-Ser,
(SEQ ID NO: 20)
Ac-Pro-Asp-(Phe-Asp)5-Pro-NH2,
(SEQ ID NO: 21)
Pro-Asp-(Phe-Asp)6,
(SEQ ID NO: 22)
(Phe-Asp)6,
(SEQ ID NO: 23)
Pro-Glu-(Phe-Glu)5-Pro,
(SEQ ID NO: 24)
Pro-Asp-(Phe-Asp)5-Pro-NH2,
(SEQ ID NO: 25)
(Phe-Glu)5,
(SEQ ID NO: 26)
(Phe-Glu)6,
(SEQ ID NO: 27)
(Phe-Glu)7,
(SEQ ID NO: 28)
Pro-Asp-(Phe-Asp)4,
(SEQ ID NO: 29)
Pro-Asp-(Phe-Asp)6,
(SEQ ID NO: 30)
Pro-Asp-(Phe-Asp)8,
(SEQ ID NO: 31)
(Phe-Asp)5,
(SEQ ID NO: 32)
(Phe-Asp)6,
(SEQ ID NO: 33)
(Phe-Asp)7,
(SEQ ID NO: 34)
Pro-Asp-(Phe-Asp)5-Pro-Arg-Gly-Asp-Ser,
(SEQ ID NO: 35)
Pro-(Phe-Asp)3-Pro,
and
(SEQ ID NO: 36)
Pro-(Phe-Asp)3-Pro-(Gly)3-Arg-Gly-Asp-Ser,
or a salt thereof.

### Claim 65 (depends on 64)

The dermatological composition of claim 64, wherein the at least one amphiphilic peptide comprises a sequence as set forth in SEQ ID NO: 1, or a salt thereof.

### Claim 66 (depends on 62)

The dermatological composition of claim 62, formulated for topical administration in the form of a hydrogel.

### Claim 67 (depends on 62)

A method for treating an epidermal condition related to aging selected from the group consisting of elastosis, atrophy of the skin, fine lines, wrinkles, enlarged pores, hyperpigmentation, hypopigmentation, sagging skin, rough skin, and dry skin, or a method for treating a skin condition selected from the group consisting of cuts, wounds, burns, insect bites, jellyfish stings, a rash, skin allergic responses, and skin lesions, the method comprising the step of locally administering to a subject in need thereof an effective amount of the dermatological composition of claim 62.