Peptide for inducing regeneration of tissue and use thereof

• US 10,550,165 B2
• Filed: 08/30/2017
• Issued: 02/04/2020
• Est. Priority Date: 04/26/2011
• Status: Active Grant

• Current Assignee: Osaka University, StemRIM Inc.
• Original Assignee: StemRIM Inc.
• Inventors: Tamai, Katsuto, Yamazaki, Takehiko, Kanezaki, Tsutomu, Sakurai, Shigeru, Noguchi, Yukiko, Endo, Mayumi, Hamabuchi, Natsumi, Naito, Kana
• Primary Examiner(s): Belyavskyi, Michail A
• Application Number:
  US15/691,017
• Publication Number:
  US 20180072785A1
• Time in Patent Office: 888 Days
• Field of Search: None
• 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. A peptide selected from the group consisting of:

A) a peptide that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO;

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 1 to 52 in the amino acid sequence of SEQ ID NO;

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

(1) the amino acid sequence of position 2 to position 25 in the amino acid sequence of SEQ ID NO;

1;

(2) the amino acid sequence of position 11 to position 34 in the amino acid sequence of SEQ ID NO;

1; and

(3) the amino acid sequence of position 17 to position 44 in the amino acid sequence of SEQ ID NO;

1;

B) a peptide that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO;

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 1 to 25 or positions 17 to 44 in the amino acid sequence of SEQ ID NO;

1, and comprises the amino acid sequence of position 17 to position 25 in the amino acid sequence of SEQ ID NO;

1;

C) a peptide that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO;

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 1 to 205 in the amino acid sequence of SEQ ID NO;

1, and comprises the amino acid sequence of position 89 to position 195 in the amino acid sequence of SEQ ID NO;

1;

D) a peptide that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO;

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 45 to 215 in the amino acid sequence of SEQ ID NO;

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

(1) the amino acid sequence of position 85 to position 169 in the amino acid sequence of SEQ ID NO;

1;

(2) the amino acid sequence of position 89 to position 185 in the amino acid sequence of SEQ ID NO;

1; and

(3) the amino acid sequence of position 93 to position 215 in the amino acid sequence of SEQ ID NO;

1; and

E) a peptide that consists of any of the amino acid sequences below;

(1) the amino acid sequence of position 1 to position 44 in the amino acid sequence of SEQ ID NO;

1;

(2) the amino acid sequence of position 1 to position 70 in the amino acid sequence of SEQ ID NO;

1;

(3) the amino acid sequence of position 1 to position 84 in the amino acid sequence of SEQ ID NO;

1;

(4) the amino acid sequence of position 1 to position 170 in the amino acid sequence of SEQ ID NO;

1;

(5) the amino acid sequence of position 1 to position 185 in the amino acid sequence of SEQ ID NO;

1;

(6) the amino acid sequence of position 1 to position 195 in the amino acid sequence of SEQ ID NO;

1;

(7) the amino acid sequence of position 2 to position 44 in the amino acid sequence of SEQ ID NO;

1;

(8) the amino acid sequence of position 2 to position 70 in the amino acid sequence of SEQ ID NO;

1,

(9) the amino acid sequence of position 2 to position 84 in the amino acid sequence of SEQ ID NO;

1;

(10) the amino acid sequence of position 2 to position 170 in the amino acid sequence of SEQ ID NO;

1;

(11) the amino acid sequence of position 2 to position 185 in the amino acid sequence of SEQ ID NO;

1;

(12) the amino acid sequence of position 2 to position 195 in the amino acid sequence of SEQ ID NO;

1;

(13) the amino acid sequence of position 17 to position 25 in the amino acid sequence of SEQ ID NO;

1;

(14) the amino acid sequence of position 45 to position 84 in the amino acid sequence of SEQ ID NO;

1;

(15) the amino acid sequence of position 85 to position 169 in the amino acid sequence of SEQ ID NO;

1;

(16) the amino acid sequence of position 89 to position 185 in the amino acid sequence of SEQ ID NO;

1;

(17) the amino acid sequence of position 89 to position 195 in the amino acid sequence of SEQ ID NO;

1; and

(18) the amino acid sequence of position 93 to position 215 in the amino acid sequence of SEQ ID NO;

1.

2. The peptide of claim 1, that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO:

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 1 to 52 in the amino acid sequence of SEQ ID NO;

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

(1) the amino acid sequence of position 2 to position 25 in the amino acid sequence of SEQ ID NO;

1;

(2) the amino acid sequence of position 11 to position 34 in the amino acid sequence of SEQ ID NO;

1; and

(3) the amino acid sequence of position 17 to position 44 in the amino acid sequence of SEQ ID NO;

1.

3. The peptide of claim 1, that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO:

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 1 to 25 or positions 17 to 44 in the amino acid sequence of SEQ ID NO;

1, and comprises the amino acid sequence of position 17 to position 25 in the amino acid sequence of SEQ ID NO;

1.

4. The peptide of claim 1, that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO:

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 1 to 205 in the amino acid sequence of SEQ ID NO;

1, and comprises the amino acid sequence of position 89 to position 195 in the amino acid sequence of SEQ ID NO;

1.

5. The peptide of claim 1, that consists of a portion of an HMGB1 protein of the amino acid sequence of SEQ ID NO:

1 and has an activity of stimulating migration of a cell, wherein the peptide consists of the whole or part of the amino acid sequence of positions 45 to 215 in the amino acid sequence of SEQ ID NO;

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

(1) the amino acid sequence of position 85 to position 169 in the amino acid sequence of SEQ ID NO;

1;

(2) the amino acid sequence of position 89 to position 185 in the amino acid sequence of SEQ ID NO;

1; and

(3) the amino acid sequence of position 93 to position 215 in the amino acid sequence of SEQ ID NO;

1.

6. The peptide according to claim 1, that consists of any of the amino acid sequences below:

(1) the amino acid sequence of position 1 to position 44 in the amino acid sequence of SEQ ID NO;

1;

(2) the amino acid sequence of position 1 to position 70 in the amino acid sequence of SEQ ID NO;

1,

(3) the amino acid sequence of position 1 to position 84 in the amino acid sequence of SEQ ID NO;

1;

(4) the amino acid sequence of position 1 to position 170 in the amino acid sequence of SEQ ID NO;

1;

(5) the amino acid sequence of position 1 to position 185 in the amino acid sequence of SEQ ID NO;

1;

(6) the amino acid sequence of position 1 to position 195 in the amino acid sequence of SEQ ID NO;

1;

(7) the amino acid sequence of position 2 to position 44 in the amino acid sequence of SEQ ID NO;

1;

(8) the amino acid sequence of position 2 to position 70 in the amino acid sequence of SEQ ID NO;

1;

(9) the amino acid sequence of position 2 to position 84 in the amino acid sequence of SEQ ID NO;

1;

(10) the amino acid sequence of position 2 to position 170 in the amino acid sequence of SEQ ID NO;

1;

(11) the amino acid sequence of position 2 to position 185 in the amino acid sequence of SEQ ID NO;

1;

(12) the amino acid sequence of position 2 to position 195 in the amino acid sequence of SEQ ID NO;

1;

(13) the amino acid sequence of position 17 to position 25 in the amino acid sequence of SEQ ID NO;

1;

(14) the amino acid sequence of position 45 to position 84 in the amino acid sequence of SEQ ID NO;

1;

(15) the amino acid sequence of position 85 to position 169 in the amino acid sequence of SEQ ID NO;

1;

(16) the amino acid sequence of position 89 to position 185 in the amino acid sequence of SEQ ID NO;

1;

(17) the amino acid sequence of position 89 to position 195 in the amino acid sequence of SEQ ID NO;

1; and

(18) the amino acid sequence of position 93 to position 215 in the amino acid sequence of SEQ ID NO;

1.

7. The peptide of claim 1, which is a synthetic peptide.

8. The peptide of claim 1, which is a peptide produced using a cell.

9. The peptide of claim 1, which is a peptide to which a tag is added.

10. The peptide of claim 1, which is a peptide to which a tag-derived peptide fragment is added.

11. A composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier or additive.

12. The composition of claim 11, wherein the pharmaceutically acceptable carrier or additive is selected from the group consisting of surfactant, excipient, colorant, perfume, preservative, stabilizer, buffer, suspending agent, isotonizing agent, binder, disintegrant, lubricant, flow promoter, and flavoring agent.

13. The composition of claim 11, wherein the pharmaceutically acceptable carrier or additive is selected from the group consisting of light anhydrous silicic acid, lactose, crystalline cellulose, mannitol, starch, carmellose calcium, carmellose sodium, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylacetaldiethylamino acetate, polyvinylpyrrolidone, gelatin, medium-chain fatty acid triglyceride, polyoxyethylene hydrogenated castor oil 60, white sugar, carboxymethyl cellulose, corn starch, and inorganic salt.