Bone delivery conjugates and method of using same to target proteins to bone
AssigneeEnobia Pharma Inc.
InventorsPhilippe Crine, Guy Boileau, Isabelle Lemire, Thomas P. Loisel
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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.
Claims17
An isolated nucleic acid molecule encoding a protein comprising a structure selected from the group consisting of:
- (i) X-Dn-Y-sALP-Z;
- and
- (ii) 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 alkaline phosphatase;
- and
- said protein is catalytically competent to allow formation of hydroxyapatite crystals in bone.
An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of:
- (a) the nucleic acid sequence of SEQ ID NO:
- 7;
- (b) a nucleic acid sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 8;
- (c) a nucleic acid sequence completely complementary to the nucleic acid sequence of (a) or (b);
- and
- (d) a nucleic acid sequence which hybridizes under high stringency conditions to any of the nucleic acid sequences of (a), (b) or (c), wherein said high stringency conditions comprise pre-hybridization and hybridization in 6×SSC, 5×Denhardt's reagent, 0.5% SDS and 100 mg/ml of denatured fragmented salmon sperm DNA at 68° C.;
- and washes in 2×SSC and 0.5% SDS at room temperature for 10 minutes;
- in 2×SSC and 0.1% SDS at room temperature for 10 minutes;
- and in 0.1×SSC and 0.5% SDS at 65° C. three times for five minutes;
- wherein said nucleic acid molecule or its complement encodes a protein that is catalytically competent to allow formation of hydroxyapatite crystals in bone.
Dependencies are inferred from the claim text.