Compositions for treating pathological calcification conditions, and methods using same
The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.
1. An isolated soluble ecto-nucleotide pyrophosphate/phosphodiesterase (ENPP1) fusion polypeptide comprising an ENPP1 catalytic domain joined to human IgG Fc through a peptide linker consisting of three amino acids, wherein said soluble ENPP1 fusion polypeptide is enzymatically active.
2. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said peptide linker is LIN.
3. The isolated soluble ENPP1 fusion polypeptide of claim 1 , which further comprises an ENPP1 nuclease domain.
4. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said human IgG Fc is defined by the amino acid sequence set forth as SEQ ID NO: 26.
5. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said soluble ENPP1 fusion polypeptide comprises an ENPP1 polypeptide segment defined by amino acid residues 93-925 of SEQ ID NO: 16.
6. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said soluble ENPP1 fusion polypeptide is defined by amino acid residues 93-1155 of SEQ ID NO: 16.
7. The isolated soluble ENPP1 fusion polypeptide of claim 5 , wherein said peptide linker connects the C-terminus of said ENPP1 polypeptide segment with the N terminus of said human IgG Fc.
8. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said soluble ENPP1 fusion polypeptide comprises an ENPP1 polypeptide segment defined by amino acid residues 23-852 of SEQ ID NO: 18.
9. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said soluble ENPP1 fusion polypeptide is defined by amino acid residues 23-1082 of SEQ ID NO: 18.
10. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said soluble ENPP1 fusion polypeptide comprises an ENPP1 polypeptide segment defined by amino acid residues 23-852 of SEQ ID NO: 20.
11. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said soluble ENPP1 fusion polypeptide is defined by amino acid residues 23-1079 of SEQ ID NO: 20.
12. The isolated soluble ENPP1 fusion polypeptide of claim 1 , wherein said ENPP1 catalytic domain is defined by amino acid residues 186-586 of SEQ ID NO: 1.
13. The isolated soluble ENPP1 fusion polypeptide of claim 3 , wherein said ENPP1 nuclease domain is defined by amino acid residues 524-885 of SEQ ID NO: 1.
14. The isolated soluble fusion polypeptide of claim 1 , wherein said enzymatically active soluble ENPP1 fusion polypeptide hydrolyzes ATP.
15. A composition comprising an isolated soluble ecto-nucleotide pyrophosphate/phosphodiesterase (ENPP1) fusion polypeptide comprising an ENPP1 catalytic domain joined to human IgG Fc through a peptide linker consisting of three amino acids, wherein said soluble ENPP1 fusion polypeptide is enzymatically active.