Npp1 fusion proteins

Abstract

The present invention provides a novel fusion polypeptide containing a catalytic domain of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

1 - 38 . (canceled) 
     
     
         39 . An isolated polypeptide comprising an ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) component, wherein the NPP1 component comprises a cysteine-rich region and a C-terminal catalytic domain of NPP1, said isolated polypeptide lacks an N-terminal cytosolic domain and a transmembrane domain, wherein said isolated polypeptide has NPP1 enzymatic activity. 
     
     
         40 . The polypeptide of  claim 39 , wherein said catalytic domain of NPP1 comprises P99 through D925 of SEQ ID NO: 1. 
     
     
         41 . The polypeptide of  claim 39 , wherein said polypeptide further comprises an Fc region of an immunoglobulin. 
     
     
         42 . The polypeptide of  claim 39 , wherein said polypeptide further comprises a signal peptide. 
     
     
         43 . The polypeptide of  claim 39 , wherein said polypeptide further comprising a targeting moiety. 
     
     
         44 . The polypeptide of  claim 43 , wherein said targeting moiety comprises at least four consecutive aspartic acid residues. 
     
     
         45 . The polypeptide of  claim 41 , wherein polypeptide further comprises a linker between said C-terminal catalytic domain and said Fc region. 
     
     
         46 . The polypeptide of  claim 45 , wherein said linker comprises 1 to about 20 amino acid residues in length. 
     
     
         47 . An isolated nucleic acid encoding a polypeptide comprising an ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) component, wherein the NPP1 component comprises a cysteine-rich region and a C-terminal catalytic domain of NPP1, said isolated polypeptide lacks an N-terminal cytosolic domain and a transmembrane domain, wherein said isolated polypeptide has NPP1 enzymatic activity. 
     
     
         48 . A replication or expression vector carrying the isolated nucleic acid of  claim 47 . 
     
     
         49 . A host cell transformed with the replication or expression vector according to  claim 48 . 
     
     
         50 . The host cell of  claim 49 , wherein said host cell is selected from the group consisting of CHO cell, HEK293 cell, or COS cell. 
     
     
         51 . A method of treating a disorder in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising an isolated polypeptide comprising an ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) component, wherein the NPP1 component comprises a cysteine-rich region and a C-terminal catalytic domain of NPP1, said isolated polypeptide lacks an N-terminal cytosolic domain and a transmembrane domain, wherein said isolated polypeptide has NPP1 enzymatic activity. 
     
     
         52 . The method of  claim 51 , wherein said disorder is arterial calcification, insulin resistance, hypophosphatemic rickets, or ossification of posterior longitudinal ligament of spine. 
     
     
         53 . The method of  claim 52 , wherein said disorder is arterial calcification. 
     
     
         54 . The method of  claim 53 , wherein the arterial calcification is generalized arterial calcification of infancy.