Compositions for Treating Ectopic Calcification Disorders, and Methods Using Same

A method of reducing or preventing progression of pathological ossification in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polypeptide comprising a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) polypeptide, whereby pathological ossification in the subject is reduced or progression of pathological ossification in the subject is prevented.

A method of treating a subject having ecto-nucleotide pyrophosphate/phosphodiesterase-1 (ENPP1) deficiency or ENPP1-associated disease, the method comprising administering to the subject a therapeutically effective amount of an isolated recombinant ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) polypeptide.

A method of treating a subject having low plasma pyrophosphate (PPi) in the range of about 500 nM to 1 μM, the method comprising administering to the subject a therapeutically effective amount of an isolated recombinant ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) polypeptide, whereby the administering results in a rise in the level of plasma PPi in the subject to about 3 μM.

A method of producing soluble ENPP3 polypeptide fusion from cells comprising an ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) precursor polypeptide fusion, wherein the ENPP3 precursor polypeptide fusion comprises a signal peptide and a C terminal domain selected from the group consisting of a human IgG Fc domain and human serum albumin, the method comprising culturing the cells in medium to permit secretion from the cells into medium of a soluble ENPP3 polypeptide fusion comprising the human IgG Fc domain or human serum albumin domain, wherein the ENPP3 precursor polypeptide fusion is proteolytically processed upon secretion from the cells to yield the soluble ENPP3 polypeptide fusion.

An isolated cell comprising ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) precursor polypeptide fusion, wherein the ENPP3 precursor polypeptide fusion comprises a signal peptide and a C terminal domain selected from the group consisting of a human IgG Fc domain and albumin, wherein the ENPP3 precursor polypeptide fusion protein is proteolytically processed upon secretion from the cell to yield a soluble ENPP3 polypeptide fusion comprising the human IgG Fc domain or albumin domain.

An isolated polypeptide comprising ectonucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) extracellular domain and a C terminal domain selected from the group consisting of a human IgG Fc domain and human serum albumin.