Modified Human Growth Hormone Polypeptides and Their Uses

Abstract

Modified human growth hormone polypeptides and uses thereof are provided.

1 - 100 . (canceled) 
     
     
         101 . A pharmaceutical formulation of a human growth hormone (hGH) variant comprising one or more non-naturally encoded amino acids wherein the non-naturally encoded amino acids are substituted at positions selected from the group consisting of 35, 92, 131, 134, 143 and 145 of SEQ ID NO: 2 and the non-naturally encoded amino acids have the structure: 
       
         
           
           
               
               
           
         
         wherein R3 is any substituent other than one used in the twenty natural amino acids; 
         wherein each of R1 and R2 is one or more amino acids; and 
         wherein each non-naturally encoded amino acid is linked to a water soluble polymer and wherein the serum half-life of the linked variant is at least two-fold greater than the serum half-life of a wild type hGH protein and wherein said formulation has a concentration between 8 mg/mL and 14 mg/mL. 
       
     
     
         102 . A pharmaceutical formulation of a human growth hormone (hGH) variant comprising one or more non-naturally encoded amino acids wherein the non-naturally encoded amino acids are substituted at positions selected from the group consisting of 35, 92, 131, 134, 143 and 145 of SEQ ID NO: 2 and the non-naturally encoded amino acids have the structure: 
       
         
           
           
               
               
           
         
         wherein R3 is any substituent other than one used in the twenty natural amino acids; 
         wherein each of R1 and R2 is one or more amino acids; and 
         wherein each non-naturally encoded amino acid is linked to a water soluble polymer, and wherein the serum half-life of the linked variant is at least two-fold greater than the serum half-life of a wild type hGH protein and wherein said formulation has a concentration between 8 mg/mL and 10 mg/mL and said formulation's viscosity allows for 1 mL to be injected through a 27 gauge needle with 4 lbs of force in 5 seconds or less.