Bone delivery conjugates and method of using same to target proteins to bone

1. A bone delivery conjugate having a structure selected from the group consisting of:

A) X-D n -Y-protein-Z; and

B) Z-protein-Y-D n -X,

wherein the protein is a soluble alkaline phosphatase (sALP) that is not a soluble form of a tissue non-specific alkaline phosphatase;

wherein X is absent or is an amino acid sequence of at least one amino acid;

Y is absent or is an amino acid sequence of at least one amino acid;

Z is absent or is an amino acid sequence of at least one amino acid; and

D n is a poly aspartate wherein n=10 to 16.

2. The bone delivery conjugate of claim 1 , wherein said structure is: Z-sALP-Y-D n -X.

3. The bone delivery conjugate of claim 2 , wherein n=10.

4. A bone delivery composition comprising the bone delivery conjugate of claim 1 and a pharmaceutically acceptable carrier.

5. A method of delivering a protein to bone tissue of a mammal comprising administering to said mammal an effective amount of the bone delivery conjugate of claim 1 .

6. A method of delivering ALP to bone tissue of a mammal in need thereof comprising administering to said mammal an effective amount of the bone delivery conjugate of claim 1 .

7. A method of treating a condition or disease related to a bone defect characterized by a lack of or an insufficient amount of functional alkaline phosphatase comprising administering to a mammal in need thereof the conjugate of claim 1 , said conjugate being in a pharmaceutically acceptable carrier.

8. The method of claim 7 , wherein the condition or disease is hypophosphatasia.