Therapeutic agents comprising elastic peptides

Abstract

The present invention provides therapeutic agents and compositions comprising elastic peptides and therapeutic proteins. Such peptides exhibit a flexible, extended conformation. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist (e.g., GLP-1, exendin), insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

1 . A pharmaceutical composition comprising an effective amount of a fusion construct, the fusion construct comprising,
 a plurality of elastic peptide components of the formula (VPGXG) 15-150 , where X is an independently selected amino acid, and   a plurality of target molecule-binding segments.   
     
     
         2 . The composition of  claim 1 , wherein at least one target molecule-binding segment targets a cell type. 
     
     
         3 . The composition of  claim 2 , wherein the cell type is a cancer cell. 
     
     
         4 . The composition of  claim 1 , wherein the composition is for systemic administration. 
     
     
         5 . The composition of  claim 1 , wherein X is independently selected from Val, Ile, Leu, Ala, Gly, and Trp. 
     
     
         6 . The composition of  claim 1 , wherein the fusion construct has a transition temperature of between 35 and 60° C. 
     
     
         7 . The composition of  claim 6 , wherein the fusion construct has a transition temperature of from 38 to 45° C. 
     
     
         8 . The composition of  claim 1 , wherein the fusion construct has a transition temperature of less than 37° C.