Human 3 relaxin

Abstract

Human H3 preprorelaxin, human H3 prorelaxin, human H3 relaxin, human relaxin analogues having a modified A chain and/or a modified B chain are described. Also described are nucleic acid sequences encoded human H3 preprorelaxin, human H3 prorelaxin, human H3 relaxin, human relaxin analogues. Also described are methods for the treatment of conditions responsive to administration of H3 relaxin or analogues thereof.

1 .- 22 . (canceled) 
     
     
         23 . A method treating of a disease related to uncontrolled or abnormal collagen or fibronectin formation in a subject, the method comprising administering a therapeutically effective amount of human H3 relaxin, or an analogue thereof, to the subject. 
     
     
         24 . The method according to  claim 23  wherein the human H3 relaxin or analogue thereof is human H3 relaxin, human H3 prorelaxin, human H3 preprorelaxin, or the constitutive A, B or C peptide chains thereof. 
     
     
         25 . The method according to  claim 24  wherein the human H3 relaxin or a human H3 relaxin analogue thereof comprises an A chain and a B chain,
 the A chain comprising SEQ ID NO:4 or an amino acid sequence truncated by up to about 9 amino acids from the N-terminus of the SEQ ID NO:4, 
 the B chain comprising SEQ ID NO:2 or an amino acid sequence truncated by up to 9 amino acids from the N-terminus of SEQ ID NO:2 and/or up to about 5 amino acids from the C-terminus of SEQ ID NO:2, and 
 wherein the A and B chains are linked by disulphide bonds between A11-B10 and A24-B22, and wherein the human H3 relaxin or analogue thereof has relaxin bioactivity. 
 
     
     
         26 . The method according to  claim 23  wherein the human H3 relaxin analogue comprises a modified A chain and/or a modified B chain,
 the modified A chain comprising SEQ ID NO:4 wherein the C-terminus is an amide derivative and/or the Lys at position 12 is replaced with Glu, and/or the Glu at position 19 is replaced with Gln, 
 the modified B chain comprising SEQ ID NO:2 wherein the C-terminus is an amide derivative, and/or the Ala at position 2 is replaced with Pro, and/or the Arg at position 8 is replaced with Lys, and 
 wherein when both the modified A and B chains are present, the modified A and B chains are linked by disulphide bonds between A11-B10 and A24-B22, and wherein the human H3 relaxin analogue has relaxin bioactivity. 
 
     
     
         27 . The method according to  claim 23  wherein the disease is fibrosis. 
     
     
         28 . The method according to  claim 27  wherein the fibrosis is selected from the group consisting of fibrosis of the lung, cardiovascular system, kidneys, genitourinary tract, gastrointestinal system, cutaneous system, rheumatologic system and hepatobiliary system. 
     
     
         29 . The method according to  claim 28  wherein the fibrosis is selected from pulmonary fibrosis, cardiovascular fibrosis, cardiac fibrosis, renal fibrosis, the group consisting of and interstitial fibrosis. 
     
     
         30 . The method according to  claim 23  wherein the human 113 relaxin or analogue thereof is administered in association with one or more pharmaceutically acceptable carriers, diluents, or excipients.