Bone delivery conjugates and method of using same to target proteins to bone
AssigneeAlexion Pharmaceuticals, Inc.
InventorsPhilippe Crine, Guy Boileau, Isabelle Lemire, Thomas P. Loisel
Life of this patent
Estimating the term…
Abstract
A bone delivery conjugate having a structure selected from the group consisting of: A) X-Dn-Y-protein-Z; and B) 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; and Dn is a poly aspartate wherein n=10 to 16. Compositions comprising same and methods of use thereof.
Claims49
A bone delivery conjugate comprising a structure selected from the group consisting of:
- A) X-Dn-Y-sALP-Z;
- and
- B) Z-sALP-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;
- said sALP is a soluble tissue non-specific alkaline phosphatase;
- and
- said bone delivery conjugate is catalytically competent to improve skeletal mineralization in bone.
A bone delivery composition comprising a pharmaceutically acceptable carrier and a bone delivery conjugate comprising a structure selected from the group consisting of:
- A) X-Dn-Y-sALP-Z;
- and
- B) Z-sALP-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;
- said sALP is a soluble tissue non-specific alkaline phosphatase;
- and
- said bone delivery conjugate is catalytically competent to improve skeletal mineralization in bone.
A method of delivering a protein to bone tissue of a mammal comprising administering to said mammal an effective amount of a bone delivery conjugate comprising a structure selected from the group consisting of:
- A) X-Dn-Y-sALP-Z;
- and
- B) Z-sALP-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;
- said sALP is a soluble tissue non-specific alkaline phosphatase;
- and
- said bone delivery conjugate is catalytically competent to improve skeletal mineralization in bone.
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 an effective amount of a bone delivery conjugate comprising a structure selected from the group consisting of:
- A) X-D-Y-sALP-Z;
- and
- B) Z-sALP-Y-D-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;
- said sALP is a soluble tissue non-specific alkaline phosphatase;
- and
- said bone delivery conjugate is catalytically competent to improve skeletal mineralization in bone,
- wherein the conjugate is in a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.