Bone delivery conjugates and method of using same to target proteins to bone
View Patent ↗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 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. Compositions comprising same and methods of use thereof.
1. A bone delivery conjugate comprising the structure: Z-protein-Y-Dn-X,
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;
Dn is a poly aspartate wherein n=10 to 16; and
wherein said protein is a secreted soluble form of an alkaline phosphatase (sALP) having an amino acid sequence encoded by the sequence as set forth in SEQ ID NO: 5.
2. A bone delivery composition comprising the bone delivery conjugate of claim 1 , and a pharmaceutically acceptable carrier.
3. The bone delivery conjugate of claim 1 , wherein Y is an amino acid sequence of at least one amino acid and X and Z are absent.
4. The bone delivery conjugate of claim 3 , wherein n is 10.
5. The bone delivery conjugate of claim 1 , wherein n is 10.
6. A method of delivering ALP to bone tissue of a mammal in need thereof comprising administering to said mammal an effective amount of a bone delivery conjugate comprising the structure: Z-protein-Y-Dn-X,
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;
Dn is a poly aspartate wherein n=10 to 16; and
wherein said protein is a secreted soluble form of an alkaline phosphatase (sALP) having an amino acid sequence encoded by the sequence as set forth in SEQ ID NO: 5.
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 a conjugate comprising the structure: Z-protein-Y-Dn-X,
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;
Dn is a poly aspartate wherein n=10 to 16; and
wherein said protein is a secreted soluble form of an alkaline phosphatase (sALP) having an amino acid sequence encoded by the sequence as set forth in SEQ ID NO: 5; and
and wherein the conjugate is in a pharmaceutically acceptable carrier.
8. The method of claim 7 , wherein the condition or disease is hypophosphatasia.