Modified growth hormone polypeptides

Abstract

We describe modified growth hormone fusion proteins and dimers comprising said fusion proteins; nucleic acid molecules encoding said proteins and methods of treatment that use said proteins in the treatment of conditions that result from growth hormone excess.

1 . An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of:
 the nucleic acid sequence set forth as SEQ ID NO:19; and the nucleic acid sequence set forth as SEQ ID NO:20.   
     
     
         2 . An isolated polypeptide encoded by an isolated nucleic acid molecule comprising the nucleic acid sequence set forth as SEQ ID NO: 19 or SEQ ID NO: 20. 
     
     
         3 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
 the amino acid sequence set forth as SEQ ID NO:21; and   the amino acid sequence set forth as SEQ ID NO:31,   wherein said polypeptide has growth hormone receptor antagonist activity.   
     
     
         4 . A homodimer comprising two identical polypeptides, wherein each of the two polypeptides comprises the amino acid sequence set forth as SEQ ID NO: 21; or SEQ ID NO: 31. 
     
     
         5 . A vector comprising the nucleic acid molecule according to  claim 1 . 
     
     
         6 . An isolated host cell transfected or transformed with a vector according to  claim 5 . 
     
     
         7 . A pharmaceutical composition comprising a polypeptide according to  claim 3 , and an excipient or a carrier. 
     
     
         8 . A composition according to  claim 7 , comprising a further therapeutic agent. 
     
     
         9 . A method to treat a human subject suffering from growth hormone excess comprising
 administering to the human subject an effective amount of the polypeptide of  claim 3 , thereby treating the growth hormone excess in the human subject.   
     
     
         10 . The method according to  claim 9 , wherein said polypeptide is administered intravenously. 
     
     
         11 . The method according to  claim 10 , wherein said polypeptide is administered subcutaneously. 
     
     
         12 . The method according to  claim 10 , wherein said polypeptide is administered daily or at two day intervals. 
     
     
         13 . The method according to  claim 10 , wherein said polypeptide is administered at weekly intervals. 
     
     
         14 . The method according to  claim 10 , wherein said polypeptide is administered at bi-weekly intervals. 
     
     
         15 . The method according to  claim 10 , wherein said polypeptide is administered at monthly intervals. 
     
     
         16 . The method according to  claim 10 , wherein said growth hormone excess results in acromegaly. 
     
     
         17 . The method according  claim 10 , wherein said growth hormone excess results in gigantism. 
     
     
         18 . A method to treat a human subject suffering from cancer associated with excess growth hormone activity comprising administering to the human subject an effective amount of at least one polypeptide according to  claim 3 , thereby treating the cancer in the human subject. 
     
     
         19 . The method according to  claim 18 , wherein the cancer is prostate cancer. 
     
     
         20 . The isolated polypeptide of  claim 3 , comprising the amino acid sequence set forth as SEQ ID NO: 21. 
     
     
         21 . An isolated polynucleotide encoding a polypeptide comprising the amino acid sequence set forth as SED ID NO: 21. 
     
     
         22 . The isolated polynucleotide of  claim 2 , comprising the polynucleotide sequence set forth as SEQ ID NO: 19.