# US 2014/0194365 A1 · Use of endostatin peptides for the treatment of fibrosis

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- Number: US 2014/0194365 A1
- Document ID: US20140194365A1
- Status: Published application
- Kind: A1
- Application number: 14/207,246
- Filed: 2014-03-12
- Published: 2014-07-10
- Earliest claimed: 2009-10-22
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Carol A. Feghali-Bostwick; Yukie Yamaguchi
- Web page: https://patentgrep.com/patent/US20140194365A1

## CPC

- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61P 17/00: Drugs for dermatological disorders
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/47: from mammals
- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- 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)
- C07K 2319/00: Fusion polypeptide
- 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

C-terminal endostatin polypeptides are disclosed herein. Polynucleotides encoding these polypeptide, host cells transformed with the polynucleotides, and methods of using these polypeptides and polynucleotides are disclosed. Uses of these polypeptide, polynucleotides and expression vectors include the treatment of fibrosis in a subject. Thus, methods are provided for treating fibrosis, including fibrosis of the skin and/or the lung.

## Claims

### Claim 1

An isolated polypeptide, comprising at least 10 consecutive amino acids and at most 47 amino acids of the amino acid sequence set forth as amino acids 133-180 of SEQ ID NO: 2, wherein the polypeptide:
a) comprises amino acids 145-153 of SEQ ID NO: 2;
b) has anti-fibrotic activity; and
c) does not comprise amino acids 1-92 of SEQ ID NO: 2; and
wherein the polypeptide is optionally amidated.

### Claim 2 (depends on 1)

The isolated polypeptide of claim 1, comprising the amino acid sequence set forth as amino acids 133-141 of SEQ ID NO: 2.

### Claim 3 (depends on 1)

The isolated polypeptide of claim 1, consisting essentially of 10 consecutive amino acids.

### Claim 4

An isolated polypeptide consisting essentially of:
a) the amino acid sequence set forth as amino acids 133-141 of SEQ ID NO: 2; or
b) the amino acid sequence set forth as amino acids 145-153 of SEQ ID NO: 2; and
wherein the polypeptide is optionally amidated.

### Claim 5 (depends on 4)

The isolated polypeptide of claim 4, consisting of:
a) the amino acid sequence set forth as amino acids 133-141 of SEQ ID NO: 2; or
b) the amino acid sequence set forth as amino acids 145-153 of SEQ ID NO: 2.

### Claim 6 (depends on 1)

The isolated polypeptide of claim 1, wherein the polypeptide has an amino terminus and a carboxy terminus, and wherein the carboxy terminus of the polypeptide is amidated.

### Claim 7 (depends on 1)

An isolated polynucleotide encoding the polypeptide of claim 1, wherein the polynucleotide is operably linked to a heterologous promoter.

### Claim 8 (depends on 5)

An isolated polynucleotide encoding the polypeptide of claim 5, wherein the polynucleotide is operably linked to a heterologous promoter.

### Claim 9 (depends on 7)

An expression vector comprising the isolated polynucleotide of claim 7.

### Claim 10 (depends on 8)

An expression vector comprising the isolated polynucleotide of claim 8.

### Claim 11 (depends on 9)

An isolated host cell transformed with the expression vector of claim 9.

### Claim 12 (depends on 10)

An isolated host cell transformed with the expression vector of claim 10.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising an effective amount of the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 4)

A pharmaceutical composition comprising an effective amount of the polypeptide of claim 4 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 7)

A pharmaceutical composition comprising the isolated polynucleotide of claim 7 and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 1)

A method of treating a subject with fibrosis, comprising
selecting a subject with fibrosis; and
administering to the subject a therapeutically effective amount of the polypeptide of claim 1,
thereby treating the subject with fibrosis.

### Claim 17 (depends on 16)

The method of claim 16, wherein the subject has a fibrosis of the skin.

### Claim 18 (depends on 17)

The method of claim 17, wherein the subject has scleroderma.

### Claim 19 (depends on 16)

The method of claim 16, wherein the subject has a keloid or hypertrophic scar.

### Claim 20 (depends on 16)

The method of claim 16, wherein the subject has idiopathic pulmonary fibrosis, morphea, Graft-Versus-Host Disease, or subepithelial fibrosis.

### Claim 21 (depends on 16)

The method of claim 16, further comprising administering to the subject a therapeutically effective amount of another therapeutic agent.

### Claim 22 (depends on 4)

A method of treating a subject with fibrosis, comprising
selecting a subject with fibrosis; and
administering to the subject a therapeutically effective amount of the polypeptide of claim 4,
thereby treating the subject with fibrosis.

### Claim 23 (depends on 22)

The method of claim 22, wherein the subject has a fibrosis of the skin.

### Claim 24 (depends on 22)

The method of claim 22, wherein the subject has scleroderma, a keloid or hypertrophic scar, idiopathic pulmonary fibrosis, morphea, Graft-Versus-Host Disease, or subepithelial fibrosis.

### Claim 25 (depends on 4)

A method for decreasing lysyl oxidase production by a cell, comprising
contacting the cell with an effective amount of the composition of claim 4, thereby decreasing the production of lysyl oxidase by the cell.

### Claim 26 (depends on 4)

A method for increasing the production of matrix metalloprotease by a cell, comprising
contacting the cell with an effective amount of the composition of claim 4, thereby increasing the production of matrix metalloprotease by the cell.