Bioactive peptides and methods of using same

• US 8,987,191 B2
• Filed: 06/21/2013
• Issued: 03/24/2015
• Est. Priority Date: 07/12/2007
• Status: Active Grant

• Current Assignee: Compugen Ltd
• Original Assignee: Compugen Ltd
• Inventors: Shemesh, Ronen, Levine, Zurit, Toporik, Amir, Hermesh, Chen, Kliger, Yossef, Wool, Assaf, Dahary, Dvir, Cohen, Yossi, Gofer, Eyal
• Primary Examiner(s): Cordero Garcia, Marcela M
• Assistant Examiner(s): Coffa, Sergio
• Application Number:
  US13/923,690
• Publication Number:
  US 20140005097A1
• Time in Patent Office: 641 Days
• US Class Current: 514/1.7
• CPC Class Codes: 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
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 14/47 : from mammals
• CPC Class Codes: C07K 14/472 : Complement proteins, e.g. anaphylatoxin, C3a, C5a
• CPC Class Codes: C07K 14/78 : Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 7/06 : having 5 to 11 amino acids
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Claims

1. A method of treating a fibrotic disorder or condition comprising administering to a subject in need thereof a peptide less than 35 amino acids in length,

wherein said peptide comprises the amino acid sequence AYAAFSV (SEQ ID NO:

2), and

wherein the peptide is delivered for a time, frequency and amount effective to decrease the fibrotic disorder or condition in the subject.

2. The method of claim 1, wherein said peptide comprises an amino acid sequence selected from the group consisting of:

3. The method of claim 1, wherein said peptide is conjugated or fused to a second non-GPCR ligand peptide or polypeptide.

4. The method of claim 1, wherein said peptide binds to and/or activates a GPCR in the LGR family of receptors or the relaxin-related family of receptors.

5. The method of claim 1, wherein said peptide is an enzymatic cleavage product of a naturally occurring protein isolated from a cell.

6. The method of claim 1, wherein said peptide is isolated from a protein recombinantly produced in a prokaryotic or eukaryotic cell, or wherein said peptide is chemically synthesized in vitro.

7. The method of claim 1 wherein said peptide includes a C-terminal amidated amino acid.

8. The method of claim 1, wherein said peptide is less than 10 amino acids in length.

9. The method of claim 1, wherein the fibrotic condition is associated with tissue remodeling following inflammation, ischemia-reperfusion injury or respiratory disease.

10. The method of claim 1, wherein the fibrotic condition is selected from the group consisting of endomyocardial fibrosis, cardiac fibrosis;

mediastinal fibrosis;

idiopathy pulmonary fibrosis;

pulmonary fibrosis;

retroperitoneal fibrosis;

fibrosis of the spleen;

fibrosis of the pancreas;

hepatic fibrosis (cirrhosis) alcohol abuse, non-alcohol related fibrosis, fibrosis resulting from a viral infection, fibromatosis;

granulomatous lung disease;

glomerulonephritis, myocardial scarring following infarction;

endometrial fibrosis, endometriosis; and

wound healing.

11. The method of claim 1, wherein the fibrotic condition is pulmonary fibrosis or idiopathic pulmonary fibrosis.

12. The method of claim 10, wherein said fibrotic condition is wound healing.

13. The method of claim 12, wherein wound healing is selected from the group consisting of injury, surgical procedures, and diabetes related wound fibrosis.

14. The method of claim 9, wherein the respiratory disease is selected from the group consisting of asthma, bronchial disease, lung diseases, chronic obstructive pulmonary disease (COPD), Acute Respiratory Distress Syndrome (ARDS), severe acute respiratory syndrome (SARS), Fibrosis related Asthma, and cystic fibrosis.

15. The method of claim 9, wherein the viral infection is caused by a virus selected from the group consisting of HAV, HBV and HCV.

16. The method of claim 1, wherein said peptide comprises the amino acid sequence of SEQ ID NO:

1.

17. The method of claim 1, wherein said peptide consists of the amino acid sequence of SEQ ID NO:

1.

18. The method of claim 1, wherein said peptide comprises the amino acid sequence of SEQ ID NO:

2.

19. The method of claim 1, wherein said peptide consists of the amino acid sequence of SEQ ID NO:

2.

20. The method of claim 9, wherein the respiratory disease is selected from the group consisting of asthma, fibrosis related asthma and chronic obstructive pulmonary disease (COPD).

21. The method of claim 1, wherein said peptide is a non-enzymatic cleavage product of a naturally occurring protein isolated from a cell.

22. The method of claim 1, wherein the peptide is a non-naturally occurring peptide.

23. The method of claim 1, wherein the peptide is administered to reach an effective concentration of 0.16 nM to 10 μ

M in the subject.

24. The method of claim 22, wherein the peptide is administered to reach an effective concentration of 0.16 nM to 10 μ

M in the subject.