Methods of treating kidney failure, and/or improving or stablizing renal function using modified relaxin polypeptides

A method of treating kidney failure, or improving or stabilizing renal function in a patient with kidney failure, comprising administering a therapeutically effective amount of a modified relaxin polypeptide to said patient wherein:

• (a) the modified relaxin polypeptide comprises the relaxin A chain polypeptide of SEQ ID NO:
• 4 and the relaxin B chain polypeptide of SEQ ID NO:
• 5 or SEQ ID NO:
• 6, substituted with a non-naturally encoded amino acid at A chain residue 1, and having zero, one or two additional amino acid changes in said relaxin A chain and having zero, one or two additional amino acid changes in said relaxin B chain, wherein each of said amino acid changes is independently a substitution, insertion or deletion;
• (b) said non-naturally encoded amino acid has the structure:
• wherein the R group is any substituent other than the side chain found in alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine;
• and
• (c) said non-naturally encoded amino acid is linked to a pharmacokinetic enhancer comprising a peptide component between 4 and 8 amino acids and a half-life extending moiety, comprising a fatty acid of Formula I:
• -Cn-COOH (Formula I)
• wherein n is between 12 and 16, and
• wherein said peptide component comprises Gluγ.