Thymosin Alpha 1 Peptide/Polymer Conjugates

Abstract

A pharmaceutical composition includes a physiologically active conjugate including a Thymosin alpha 1 (TA1) peptide conjugated to a material which increases half-life of the TA1 peptide in serum of a patient when the conjugate is administered to a patient. The material may be a substantially non-antigenic polymer. In a method of the invention, the substantially non-antigenic polymer is conjugated to a TA1 peptide. Compositions according to the invention are administered to patients in need of immune stimulation.

1 . A pharmaceutical composition comprising a physiologically active conjugate, said conjugate comprising a Thymosin alpha 1 (TA1) peptide conjugated to a material which increases half-life of the TA1 peptide in serum of a patient when said conjugate is administered to a patient wherein said conjugate retains activity of unconjugated Thymosin alpha 1 peptide of and said conjugate has greater activity in said patient as compared to unconjugated Thymosin alpha 1 peptide. 
     
     
         2 . The composition of  claim 1  wherein said material is a substantially non-antigenic polymer. 
     
     
         3 . The composition of  claim 2  wherein said polymer is PEG. 
     
     
         4 . The composition of  claim 3  wherein said PEG has a molecular weight within a range of about 200-300,000. 
     
     
         5 . The composition of  claim 4  wherein said molecular weight is about 5,000-35,000. 
     
     
         6 . The composition of  claim 5  wherein said molecular weight is about 20,000. 
     
     
         7 . The composition of  claim 2  wherein said polymer is conjugated to an N-terminal portion of the TA1 peptide. 
     
     
         8 . The composition of  claim 1  wherein said TA1 peptide is TA1. 
     
     
         9 . The composition of  claim 1 , wherein said conjugate retains NK- and T-cell stimulating activity of unconjugated Thymosin alpha 1 peptide and said conjugate has greater NK- and T-cell-stimulating activity in said patient as compared to unconjugated Thymosin alpha 1 peptide. 
     
     
         10 . A method of forming a composition as claimed in  claim 2 , comprising conjugating a substantially non-antigenic polymer to a Thymosin alpha 1 peptide. 
     
     
         11 . The method of  claim 10  wherein the polymer is conjugated to an N-terminal portion of the Thymosin alpha 1 peptide. 
     
     
         12 . The method of  claim 10  wherein the polymer is PEG. 
     
     
         13 . The method of  claim 10  wherein said PEG has a molecular weight in a range of about 200-300,000. 
     
     
         14 . The method of  claim 13  wherein said molecular weight is about 5,000-35,000. 
     
     
         15 . The method of  claim 14  wherein said molecular weight is about 20,000. 
     
     
         16 . The method of  claim 10  wherein said Thymosin alpha 1 peptide is TA1. 
     
     
         17 . A method of treatment for treating a patient in need of immune stimulation, comprising administering to said patient an immune stimulating-effective amount of the composition of  claim 1 , the composition comprising a physiologically active conjugate, said conjugate comprising a Thymosin alpha 1 (TA1) peptide conjugated to a material which increases half-life of the TA1 peptide in serum of a patient when said conjugate is administered to a patient wherein said Thymosin alpha 1 peptide of said conjugate has greater activity in said patient as compared to unconjugated Thymosin alpha 1 peptide. 
     
     
         18 . The method of  claim 17 , wherein said material is a substantially non-antigenic polymer. 
     
     
         19 . The method of  claim 17  wherein said polymer is PEG. 
     
     
         20 . The method of  claim 19  wherein said PEG has a molecular weight within a range of about 200-300,000. 
     
     
         21 . The method of  claim 20  wherein said molecular weight is about 5,000-35,000. 
     
     
         22 . The method of  claim 21  wherein said molecular weight is about 20,000. 
     
     
         23 . The method of  claim 18  wherein said polymer is conjugated to an N-terminal portion of the TA1 peptide. 
     
     
         24 . The method of  claim 17  wherein the TA1 peptide is TA1. 
     
     
         25 . The method of  claim 17 , wherein said conjugate retains NK- and T-cell stimulating activity of unconjugated Thymosin alpha 1 peptide and said conjugate has greater NK- and T-cell-stimulating activity in said patient as compared to unconjugated Thymosin alpha 1 peptide.