# US 2014/0194358 A1 · Prominin-1 peptide fragments and uses thereof

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- Number: US 2014/0194358 A1
- Document ID: US20140194358A1
- Status: Published application
- Kind: A1
- Application number: 14/064,502
- Filed: 2013-10-28
- Published: 2014-07-10
- Earliest claimed: 2008-07-28
- Assignees: Children's Medical Center Corporation
- Applicants: Children's Medical Center Corporation
- Inventors: Avner Adini; Robert D'Amato
- Web page: https://patentgrep.com/patent/US20140194358A1

## CPC

- A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Described herein are peptide compositions of a prominin-1, which have regenerative activity. As such the peptides are useful when regeneration is needed, for example, to enhance angiogenesis, increase VEGF binding to endothelial cells, promote vasodilation, enhance cell migration, enhance cell proliferation, stimulate neuronal growth, prevent neurodegeneration, and/or promote neuroregeneration.

## Claims

### Claim 1

An isolated prom-1 peptide derived from a prominin-1, wherein said peptide has regenerative activity, and wherein the peptide does not include a full-length prominin-1.

### Claim 2 (depends on 1)

The isolated peptide from claim 1, wherein said peptide's regenerative activity is promoting angiogenesis.

### Claim 3 (depends on 1)

The isolated peptide from claim 1, wherein said peptide's regenerative activity is promoting neuronal growth.

### Claim 4 (depends on 1)

The isolated peptide from claim 1, wherein said peptide's regenerative activity is promoting wound healing in tissues and/or bone.

### Claim 5 (depends on 1)

The isolated peptide from claim 1, wherein said peptide is derived from an extracellular domain of a prominin-1.

### Claim 6 (depends on 1)

The isolated prom-1 peptide from claim 1, wherein the peptide consists essentially of a peptide selected from the group consisting of: LCGNSFSGGQPS (SEQ. ID. No. 4); PNIIPVLDEIKS (SEQ. ID. No. 5); LCGVCGYDRHAT (SEQ. ID. No. 6); ITNNTSSVIIEE (SEQ. ID. No. 7); DRVQRQTTTVVA (SEQ. ID. No. 8); and CSFAYDLEAKANSLPPGNLRN (SEQ. ID. No. 9).

### Claim 7 (depends on 1)

The isolated prom-1 peptide of claim 1, wherein the peptide comprises at least 6 contiguous amino acid residues, and wherein the peptide does not include a full-length prominin-1.

### Claim 8 (depends on 1)

An isolated peptide that is a conservative amino acid substitution variant of a peptide of claim 1.

### Claim 9 (depends on 1)

A peptide that is at least 90% identical to a peptide of claim 1, wherein said peptide has regenerative activity.

### Claim 10 (depends on 1)

A peptide of claim 1, wherein said prom-1 peptide is constructed into a cyclic peptide.

### Claim 11 (depends on 1)

The peptide of claim 1, wherein the cyclic peptide comprises a formula of CX(DRVQBQTTTVVA)ZC or ACX(DRVQBQTTTVVA)ZC, wherein X or Z are each independently 0-20 amino acids, and wherein B is any one of the naturally occurring amino acid or a derivative thereof.

### Claim 12 (depends on 11)

The peptide of claim 11, wherein the glutamine (Q) at position 6 of the core (DRVQBQTTTVVA) of the cyclic peptide is substituted with any one of the known 20 amino acids other that glutamine.

### Claim 13 (depends on 1)

A peptide of claim 1, wherein the cyclic peptide is selected from the group consisting of: ACGG(DRVQBQTTTVVA)GGC (SEQ ID NO: 15), ACGG(DRVQBQTTTVVA)GGGGGGC (SEQ ID NO: 16), and CGGGGGG(DRVQBQTTTVVA)GGCA (SEQ ID NO: 17).

### Claim 14 (depends on 1)

A peptide of claim 1 with a formula of X(DRVQBQTTTVVA)Z or X(DRVQBQTTTVVA)Z, wherein X or Z are each independently 0-20 amino acids, and wherein B is any one of the naturally occurring amino acid or a derivative thereof.

### Claim 15 (depends on 13)

A peptide of claim 13 which is a conservative amino acid substitution variant or a 90% homologous variant thereof that substantially retains regenerative activity.

### Claim 16 (depends on 1)

The isolated prom-1 peptide of claim 1, wherein the peptide is conjugated to a polymer.

### Claim 17 (depends on 1)

A fusion protein comprising a peptide of claim 1, fused to a heterologous peptide or polypeptide, wherein the fusion protein is not a full-length prominin-1.

### Claim 18 (depends on 1)

A composition comprising a pharmaceutically acceptable carrier and an isolated prom-1 peptide of claim 1.

### Claim 19 (depends on 17)

A method of promoting regeneration in a tissue in need thereof, the method comprising contacting said tissue with a composition of claim 17.

### Claim 20 (depends on 18)

The method of claim 18 wherein the method is applied in the context of promoting wound healing, neuronal growth, protection or repair, tissue repair, bone repair, fertility promotion, cardiac hypertrophy, treatment of erectile dysfunction, modulation of blood pressure, revascularization after disease or trauma, tissue grafts, or tissue engineered constructs.

### Claim 21 (depends on 18)

A method of promoting neuroprotection or neural regeneration to an individual in need of neuroprotection, the method comprising contacting a neuronal cell with a composition of claim 18, wherein said contacting prevents or delays neuronal cell death relative to neuronal cell death occurring in the absence of said contacting, or wherein said contacting promotes nerve regeneration by stimulating neuronal growth.
