Methods of modulating apoptosis by administration of relaxin agonists or antagonists

• US 8,119,136 B2
• Filed: 11/12/2010
• Issued: 02/21/2012
• Est. Priority Date: 10/04/2000
• Status: Expired due to Term

• Current Assignee: Korea Medicine Research Institute
• Original Assignee: Korea Medicine Research Institute
• Inventors: Amento, Edward P., Samuel, Christian S.
• Primary Examiner(s): RAWLINGS, STEPHEN L
• Application Number:
  US12/945,685
• Publication Number:
  US 20110059108A1
• Time in Patent Office: 466 Days
• Field of Search: None
• US Class Current: 424/143.1
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2221 Relaxins
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/64 Relaxins

Abstract

The present invention relates to the discovery that relaxin is associated with the development or maturation of body tissues. Knockouts of the gene encoding relaxin result in various abnormalities in the development of various tissues. The present invention provides methods of modulating apoptosis by administering a relaxin agonist or antagonist to a subject.

Claims

1. A method of increasing apoptosis in a population of human cells expressing a human relaxin receptor, comprising:

administering to the population cells of an effective amount of an antagonist of relaxin for a period of time sufficient to increase apoptosis in the cell population expressing the relaxin receptor, as compared to the level of apoptosis in the cell population not contacted with the antagonist, wherein said antagonist of relaxin is an antibody or an antigen binding fragment thereof that specifically binds to a relaxin receptor and inhibits binding of human relaxin isoforms H1 or H2 to the receptor, thereby promoting the apoptosis of the cells.

2. The method of claim 1, wherein the antibody reduces relaxin-associated tissue remodeling.

3. The method of claim 1, wherein the cell population is from heart, brain, liver, kidney, spleen, thymus, or male reproductive tract tissue.

4. The method of claim 3, wherein the male reproductive tract tissue is of the prostate, epididymis, seminal vesicles or testes.

5. The method of claim 3, wherein the male reproductive tract tissue is prostatic tissue.

6. The method of claim 3, wherein the male reproductive tract tissue is mature.

7. The method of claim 1, wherein the cell population comprises fibroblasts, osteoblasts, monocytes, epithelial cells or endothelial cells.

8. The method of claim 1, wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a single chain antibody, a Fab, a Fab′

, a F(ab′

)2, a Fv, a humanized antibody, or a chimeric antibody.