Use of endostatin peptides for the treatment of fibrosis

Patent metadata

Field	Value
Publication number	US-9556252-B2
Application number	US-201615152468-A
Country	US
Kind code	B2
Filing date	May 11, 2016
Priority date	Oct 22, 2009
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

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.

First claim

The invention claimed is:

1. An isolated nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid encoding a polypeptide, wherein the polypeptide consists of:
a) the amino acid sequence set forth as amino acids 133-141 of SEQ ID NO: 2;
b) the amino acid sequence set forth as amino acids 133-141 of SEQ ID NO: 2 and an Fc domain;
c) the amino acid sequence set forth as amino acids 145-153 of SEQ ID NO: 2;
d) the amino acid sequence set forth as amino acids 145-153 of SEQ ID NO: 2 and an Fc domain;
e) the amino acid sequence set forth as amino acids 145-153 of SEQ ID NO: 13;
f) the amino acid sequence set forth as amino acids 145-153 of SEQ ID NO: 13 and an Fc domain;
g) the amino acid sequence set forth as amino acids 133-180 of SEQ ID NO: 2;
h) the amino acid sequence set forth as amino acids 133-180 of SEQ ID NO: 2 and an Fc domain;
i) the amino acid sequence set forth as amino acids 133-180 of SEQ ID NO: 13; or
j) the amino acid sequence set forth as amino acids 133-180 of SEQ ID NO: 13 and an Fc domain.

2. An expression vector comprising the nucleic acid molecule of claim 1 .

3. The expression vector of claim 2 , wherein the expression vector is a viral vector.

4. The expression vector of claim 2 , wherein the expression vector is a yeast expression vector.

5. The expression vector of claim 2 , wherein the expression vector is a plant expression vector.

6. The expression vector of claim 2 , wherein the promoter is inducible.

7. An isolated host cell transformed or transfected with the expression vector of claim 3 .

8. The host cell of claim 7 , wherein the host cell is a eukaryotic host cell.

9. The host cell of claim 7 , wherein the host cell is plant host cell.

10. A composition comprising an effective amount of the isolated nucleic acid molecule of claim 1 and a pharmaceutically acceptable carrier.

11. A composition comprising an effective amount of the expression vector of claim 2 and a pharmaceutically acceptable carrier.

12. A method producing a polypeptide in a host cell, comprising
transforming or transfecting a host cell with an effective amount of the expression vector of claim 2 , thereby producing the polypeptide.

13. The method of claim 12 , wherein the host cell is a eukaryotic cell.

14. The method of claim 12 , wherein the host cell is a plant cell.

15. The method of claim 12 , further comprising
isolating the polypeptide; and
amidating the polypeptide.

16. The method of claim 14 , further comprising
isolating the polypeptide; and
amidating the polypeptide.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Feghali-Bostwick Carol A
• Yamaguchi Yukie

Classifications

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K38/39 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] · CPC title

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title

• A61K38/00

  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) · CPC title