Therapeutic agents comprising elastin-like peptides

Abstract

The present invention provides therapeutic agents and compositions comprising elastin-like peptides (ELPs) and therapeutic proteins. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist, 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 - 100 . (canceled) 
     
     
         101 . A therapeutic agent comprising an insulin A chain and an insulin B chain joined by one or more disulfide bonds and produced by peptidase processing of proinsulin, wherein said insulin A chain is a recombinant fusion protein with an elastin-like peptide (ELP) comprising 120 repeats of VPGXG (SEQ ID NO: 3), where X is V, G, or A at a ratio of 5:3:2. 
     
     
         102 . The therapeutic agent of  claim 101 , wherein the insulin A chain amino acid sequence is positioned at the N-terminal end of the ELP. 
     
     
         103 . The therapeutic agent of  claim 101 , wherein the Insulin A chain is SEQ ID NO: 15. 
     
     
         104 . The therapeutic agent of  claim 101 , wherein the Insulin B chain is SEQ ID NO: 16. 
     
     
         105 . The therapeutic agent of  claim 101 , wherein the Insulin A chain is SEQ ID NO: 15 and the Insulin B chain is SEQ ID NO: 16. 
     
     
         106 . The therapeutic agent of  claim 101 , wherein the insulin A chain sequence comprises an amino acid sequence having about 5 amino acid insertions, deletions, and/or substitutions relative to SEQ ID NO: 15 and the insulin B chain sequence comprises an amino acid sequence having about 1 to 10 amino acid insertions, deletions, and/or substitutions relative to SEQ ID NO: 16. 
     
     
         107 . The therapeutic agent of  claim 101 , wherein the therapeutic agent is formulated with a pharmaceutically acceptable carrier and/or excipient. 
     
     
         108 . The therapeutic agent of  claim 107 , wherein the therapeutic agent is formulated for parenteral administration. 
     
     
         109 . A therapeutic agent comprising the amino acid sequences of SEQ ID NOs: 15 and 16 united by one or more disulfide bonds and produced by peptidase processing of proinsulin,
 wherein the amino acid sequence of SEQ ID NO: 15 is a recombinant fusion protein with an elastin-like peptide (ELP) comprising 120 repeats of VPGXG (SEQ ID NO: 3), where each X is V, G, or A at a ratio of 5:3:2.   
     
     
         110 . The therapeutic agent of  claim 109 , wherein the amino acid sequence of SEQ ID NO: 15 is positioned at the N-terminal side of the ELP. 
     
     
         111 . The therapeutic agent of  claim 109 , wherein the therapeutic agent is formulated with a pharmaceutically acceptable carrier and/or excipient. 
     
     
         112 . The therapeutic agent of  claim 109  wherein the peptidase processing comprises trypsin processing and carboxypeptidase B processing. 
     
     
         113 . The therapeutic agent of  claim 111 , wherein the therapeutic agent is formulated for parenteral administration.