Human neuregulin-1 (nrg-1) recombinant fusion protein compositions and methods of use thereof

Abstract

The present invention relates to a recombinant fusion protein comprising a fragment of the cardioprotective protein neuregulin-1 (NRG-1) fused to a monoclonal antibody (mAb) backbone and to a method of treating a disease or condition in a subject in need thereof comprising administering a therapeutically effective amount of the recombinant fusion protein or the pharmaceutical composition comprising the recombinant fusion protein disclosed herein.

What is claimed is: 
     
         1 . A method of producing a recombinant fusion protein comprising an active fragment of the cardioprotective protein neuregulin-1 (NRG-1) fused to a monoclonal antibody (mAb) backbone that is monospecific for ErbB3 (HER3), the method comprising:
 (a) transforming eukaryotic host cells with at least a first vector comprising a sequence encoding a light chain of the monoclonal antibody backbone and a sequence encoding a heavy chain of the monoclonal antibody backbone fused via its C-terminus to the N-terminus of the NRG-1 fragment;   (b) culturing the eukaryotic host cells under conditions sufficient to express the recombinant fusion protein; and   (c) purifying the recombinant fusion protein.   
     
     
         2 . The method of  claim 1 , wherein the NRG-1 fragment is fused via its N-terminus to the C-terminus of the heavy chain using a linker. 
     
     
         3 . The method of  claim 2 , wherein said linker comprises at least one copy of a Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser (SEQ ID NO: 5). 
     
     
         4 . The method of  claim 1 , wherein the C-terminus of the antibody heavy chain comprises the Fc domain of the antibody. 
     
     
         5 . The method of  claim 1 , wherein the NRG-1 fragment comprises an amino acid sequence of SEQ ID NO: 4. 
     
     
         6 . The method of  claim 1 , wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 2. 
     
     
         7 . The method  claim 1 , wherein the light chain comprises an amino acid sequence of SEQ ID NO: 3. 
     
     
         8 . The method of  claim 1 , wherein the recombinant fusion protein comprises the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 14. 
     
     
         9 . The method of  claim 1 , wherein the sequence encoding the light chain comprises SEQ ID NO: 8. 
     
     
         10 . The method of  claim 1 , wherein the sequence encoding the heavy chain comprises SEQ ID NO: 6 or 7. 
     
     
         11 . The method of  claim 1 , wherein the eukaryotic host cells comprise CHO cells. 
     
     
         12 . The method of  claim 11 , wherein the CHO cells comprise CHO-K1 cells. 
     
     
         13 . The method of  claim 1 , wherein the at least one vector comprises a first vector encoding the light chain and a second vector encoding the heavy chain fused to the NRG-1 active fragment.