Methods of modulating apoptosis by administration of relaxin agonists or antagonists

• US 9,534,034 B2
• Filed: 02/17/2012
• Issued: 01/03/2017
• Est. Priority Date: 10/04/2000
• Status: Expired due to Fees

• Current Assignee: Korea Medicine Research Institute
• Original Assignee: Korea Medicine Research Institute
• Inventors: Amento, Edward P., Samuel, Chrishan S.
• Primary Examiner(s): RAWLINGS, STEPHEN L
• Application Number:
  US13/399,620
• Publication Number:
  US 20120238499A1
• Time in Patent Office: 1,782 Days
• Field of Search: 514/1.1, 514/514, 435/375, 530/300, 530/350
• US Class Current: 1/1
• 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 for stimulating maturation of an immature male reproductive tract tissue, comprising administering to a post-pubescent male subject having a low sperm count as compared with a normal sperm count an effective amount of a human relaxin agonist, wherein the human relaxin agonist is human relaxin H2 which is a heterodimeric polypeptide comprising a first polypeptide chain comprising:

(i) amino acids 4 to 27 of SEQ ID NO;

3;

(ii) amino acids 4 to 28 of SEQ ID NO;

3;

(iii) amino acids 4 to 29 of SEQ ID NO;

3;

(iv) amino acids 4 to 30 of SEQ ID NO;

3;

(v) amino acids 4 to 31 of SEQ ID NO;

3;

(vi) amino acids 4 to 32 of SEQ ID NO;

3;

(vii) amino acids 4 to 33 of SEQ ID NO;

3;

(viii) amino acids 4 to 34 of SEQ ID NO;

3;

(ix) amino acids 4 to 35 of SEQ ID NO;

3;

or

(x) amino acids 4 to 36 of SEQ ID NO;

3 and

a second polypeptide chain comprising;

(i) amino acids 4 to 27 of SEQ ID NO;

4;

(ii) amino acids 5 to 27 of SEQ ID NO;

4;

or

(iii) amino acids 6 to 27 of SEQ ID NO;

4

for a time period sufficient to stimulate tissue maturation, wherein said maturation is an increase in the number of viable sperm cells, as compared with tissue not contacted with the relaxin agonist.

2. The method of claim 1, wherein the tissue is testicular tissue.

3. The method of claim 1, wherein the human relaxin agonist is a recombinantly produced human relaxin H2 heterodimeric polypeptide comprising a first polypeptide chain comprising amino acids 4 to 36 of SEQ ID NO:

3 and a second polypeptide chain comprising amino acids 4 to 27 of SEQ ID NO;

4.

4. The method of claim 1, wherein the administering is by infusion, injection, oral delivery, nasal delivery, intrapulmonary delivery, rectal delivery, transdermal delivery, interstitial delivery or subcutaneous delivery.

5. The method of claim 4, wherein the administering is by delayed release delivery.

6. The method of claim 2, wherein the testicular tissue is epididymal tissue, seminiferous tissue, or sperm.

7. The method of claim 1, wherein the human relaxin agonist is a human H2 relaxin heterodimeric polypeptide with a truncated B chain (relaxin H2 (B29, A24);

wherein the human H2 relaxin heterodimeric polypeptide comprises a first polypeptide chain comprising amino acids 4 to 32 of SEQ ID NO;

3 and a second polypeptide chain comprising amino acids 4 to 27 of SEQ ID NO;

4.