NPP1 FUSION PROTEINS
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 . An isolated polypeptide comprising an ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) component, wherein the NPP1 component is a portion of NPP1 that comprises the cysteine-rich region and the C-terminus catalytic domain of NPP1, but having the N-terminal cytosolic and the transmembrane domains removed, said isolated polypeptide having NPP1 enzymatic activity.
2 . (canceled)
3 . The polypeptide of claim 1 , wherein said polypeptide is a recombinant protein.
4 - 7 . (canceled)
8 . The polypeptide of claim 1 , wherein said catalytic domain of NPP1 comprises P99 through D925 of SEQ ID NO: 1.
9 - 18 . (canceled)
19 . The polypeptide of claim 1 , wherein said polypeptide further comprises an Fc region of an immunoglobulin.
20 . The polypeptide of claim 1 , wherein said polypeptide further comprises a signal peptide.
21 . The polypeptide of claim 1 , wherein said polypeptide forms a homodimer.
22 . The polypeptide of claim 1 , wherein said polypeptide protein is a monomer.
23 . An isolated nucleic acid encoding the polypeptide of claim 1 .
24 . A replication or expression vector carrying the isolated nucleic acid of claim 23 .
25 . A host cell transformed with the replication or expression vector according to claim 23 .
26 . The host cell of claim 25 , wherein said host cell is selected from the group consisting of CHO cell, HEK293 cell, or COS cell.
27 . The host cell of claim 20 , wherein said host cell is an avian tumor cell.
28 . A transgenic animal producing the polypeptide of claim 1 .
29 . The transgenic animal of claim 28 , wherein said transgenic animal is mammalian or avian.
30 . A method producing said polypeptide of claim 1 by an avian cell comprising culturing an avian cell transfected with at least one expression vector comprising a transcription unit having a nucleotide sequence encoding said polypeptide of claim 1 operably linked to a promoter and a transcriptional terminator, and wherein the cultured avian cell produces said polypeptide.
31 . (canceled)
32 . A method of treating a disorder in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising the polypeptide of claim 1 .
33 - 34 . (canceled)
35 . The method of claim 32 , wherein said disorder is arterial calcification, insulin resistance, hypophosphatemic rickets, or ossification of posterior longitudinal ligament of spine.
36 . The method of claim 35 , wherein said disorder is arterial calcification.
37 . (canceled)
38 . The method of claim 36 , wherein the arterial calcification is generalized arterial calcification of infancy.
39 . An isolated polypeptide comprising a targeting moiety and a C-terminus catalytic domain of NPP1.