PEPTIDE FOR INDUCING REGENERATION OF TISSUE AND USE THEREOF

• US 20140206619A1
• Filed: 04/03/2012
• Published: 07/24/2014
• Est. Priority Date: 04/26/2011
• Status: Active Grant

• Current Assignee: Osaka University, StemRIM Inc.
• Original Assignee: Genomix Co., Ltd., Osaka University
• Inventors: Tamai, Katsuto, Yamazaki, Takehiko, Endo, Mayumi, Kanezaki, Tsutomu, Sakurai, Shigeru, Noguchi, Yukiko, Hamabuchi, Natsumi, Naito, Kana
• Granted Patent: US 10,364,276 B2
• Time in Patent Office: Days
• US Class Current: 514/16.5
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 2319/21 : containing a His-tag
• CPC Class Codes: C07K 2319/50 : containing protease site
• CPC Class Codes: C12N 15/85 : for animal cells
• CPC Class Codes: C12N 2510/00 : Genetically modified cells

Abstract

(Objective) An objective of the present invention is to provide therapeutic agents that, in association with stimulation of PDGFRα-positive cells such as bone marrow mesenchymal stem cells, promote their mobilization into blood and accumulation in a damaged tissue, and induce tissue regeneration in a living body.

(Means for solution) Multiple peptides were synthesized, and the migration-promoting activity of each peptide was evaluated. As a result, the present inventors successfully identified multiple peptides that have migration-promoting activity on a PDGFRα-positive bone marrow mesenchymal stem cell line (MSC-1). Further, the present inventors confirmed that the identified peptides also have migration-promoting activity on skin fibroblasts, which are PDGFRα-positive cells.

Claims

1-29. -29. (canceled)

30. A method of stimulating migration of a cell, mobilizing a cell from bone marrow to peripheral blood, and/or regenerating a tissue, which comprises administering an effective amount of a substance of any one of (a) to (c) below;

(a) a peptide consisting of a portion of an HMGB1 protein and having cell migration-stimulating activity;

(b) a cell secreting the peptide of (a); and

(c) a vector into which a DNA encoding the peptide of (a) is inserted.

31. The method of claim 30, wherein the cell stimulated to migrate or mobilized from bone marrow to peripheral blood is a PDGFRα

-positive cell.

32. The method of claim 30, wherein the cell stimulated to migrate or mobilized from bone marrow to peripheral blood is a stem cell.

33. The method of claim 30, wherein the cell stimulated to migrate or mobilized from bone marrow to peripheral blood is a bone marrow cell.

34. The method of claim 30, wherein the cell stimulated to migrate or mobilized from bone marrow to peripheral blood is a bone marrow mesenchymal stem cell.

35. The method of claim 30, wherein the peptide consisting of a portion of an HMGB1 protein and having an activity of stimulating migration of a cell is a peptide consisting of the whole or part of the amino acid sequence of positions 1 to 195 or positions 1 to 185 in the amino acid sequence of any one of SEQ ID NOs:

1, 3, and 5, and having an activity of stimulating migration of a cell.

36. The method of claim 30, wherein the peptide consisting of a portion of an HMGB1 protein and having an activity of stimulating migration of a cell is a peptide comprising any of the amino acid sequences below and having an activity of stimulating migration of a cell:

(1) the amino acid sequence of position 17 to position 25 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(2) the amino acid sequence of position 45 to position 74 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(3) the amino acid sequence of position 55 to position 84 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(4) the amino acid sequence of position 85 to position 169 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5; and

(5) the amino acid sequence of position 89 to position 185 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5.

37. The method of claim 30, wherein the peptide consisting of a portion of an HMGB1 protein and having an activity of stimulating migration of a cell is a peptide having an activity of stimulating migration of a cell which consists of the whole or part of the amino acid sequence of positions 1 to 195 or positions 1 to 185 in the amino acid sequence of any one of SEQ ID NOs:

1, 3, and 5, and comprises any of the amino acid sequences below;

(1) the amino acid sequence of position 17 to position 25 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(2) the amino acid sequence of position 45 to position 74 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(3) the amino acid sequence of position 55 to position 84 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(4) the amino acid sequence of position 85 to position 169 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5; and

(5) the amino acid sequence of position 89 to position 185 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5.

38. The method of claim 30, wherein the peptide is a synthetic peptide.

39. The method of claim 30, wherein the peptide is a peptide produced using a cell.

40. The method of claim 30, wherein the peptide is a peptide to which a tag is added.

41. The method of claim 30, wherein the peptide is a peptide to which a tag-derived peptide fragment is added.

42. A method of stimulating migration of a cell, mobilizing a cell from bone marrow to peripheral blood, and/or regenerating a tissue, which comprises administering an effective amount of a peptide comprising any of the amino acid sequences below and having an activity of stimulating migration of a cell:

(1) the amino acid sequence of position 17 to position 25 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(2) the amino acid sequence of position 45 to position 74 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(3) the amino acid sequence of position 55 to position 84 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5;

(4) the amino acid sequence of position 85 to position 169 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5; and

(5) the amino acid sequence of position 89 to position 185 in the amino acid sequence of any one of SEQ ID NOs;

1, 3, and 5.

43. The method of claim 42, wherein the peptide is a synthetic peptide.

44. The method of claim 42, wherein the peptide is a peptide produced using a cell.

45. The method of claim 42, wherein the peptide is a peptide to which a tag is added.

46. The method of claim 42, wherein the peptide is a peptide to which a tag-derived peptide fragment is added.