Alexion Pharmaceuticals, Inc.

Enobia Pharma Inc.

Universitéde Montreal

Vanderbilt University

Alexion Pharmaceuticsl, Inc.

Alexion Pharma Holding

Philippe Crine

Guy Boileau

Isabelle Lemire

Thomas P Loisel

Denis Gravel

Elaref S Ratemi

Mostafa Hatam

Pierre Leonard

Marie Parat

Robert Heft

Florent Elefteriou

Simon Joubert

Hal Landy

A bone delivery conjugate having a structure selected from the group consisting of: A) X-D-Y-protein-Z; and B) Z-protein-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; and Dis a poly aspartate wherein n=10 to 16. Compositions comprising same and methods of use thereof.

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

The present invention provides methods, compositions, and kits for the treatment of neurocutaneous syndromes, such as neurofibromatosis type I; disorders associated with overactivation of FGFR3, such as achondroplasia; bone or cartilage disorders; or vascular smooth muscle disorders; or for the elongation of bone. In some embodiments, the present invention provides polypeptides having an alkaline phosphatase peptide fused to an Fc domain of an immunoglobulin or a natriuretic peptide fused to an Fc domain of an immunoglobulin. Such polypeptides can be administered to subjects, e.g., subcutaneously, to treat a neurocutaneous syndrome, a disorder associated with overactivation of FGFR3, a bone or cartilage disorder, or a vascular smooth muscle disorder, or to elongate bone. The invention also features nucleic acid molecules encoding such polypeptides and the use of the nucleic acid molecules for treating neurocutaneous syndromes, disorders associated with overactivation of FGFR3, bone or cartilage disorders, or vascular smooth muscle disorders, or for elongating bone.

Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof

The present invention provides methods, compositions, and kits for the treatment of matrix mineralization disorders such as hypophosphatasia. In particular, the present invention provides polypeptides having a soluble alkaline phosphatase fused to an Fc domain of an immunoglobulin. Such polypeptides can be administered to patients, e.g., subcutaneously, to treat hypophosphatasia using enzyme replacement therapy. The invention also features nucleic acids encoding such polypeptides and the use of the nucleic acids for treating matrix mineralization disorders.

Methods, compositions, and kits for the treatment of matrix mineralization disorders

The present invention provides methods, compositions, and kits for the treatment of disorders associated with overactivation of FGFR3, such as achondroplasia; bone or cartilage disorders; or vascular smooth muscle disorders, or for the elongation of bone. In some embodiments, the present invention provides polypeptides having a natriuretic peptide fused to an Fc domain of an immunoglobulin. Such polypeptides can be administered to subjects, e.g., subcutaneously, to treat a disorder associated with overactivation of FGFR3, a bone or cartilage disorder, or a vascular smooth muscle disorder, or to elongate bone. The invention also features nucleic acid molecules encoding such polypeptides and the use of the nucleic acid molecules for treating disorders associated with overactivation of FGFR3, bone or cartilage disorders, or vascular smooth muscle disorders, or for elongating bone.

Compositions comprising natriuretic peptides and methods of use thereof

This invention relates to a soluble form of PHEX, PHEX being a type II integral membrane glycoprotein. This enzyme is the gene product of a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. To produce a soluble form of PHEX, the transmembrane anchor domain has been modified to encode a signal peptidase coding sequence. The soluble PHEX therefore comprises the active ectodomain. An inactive mutant of PHEX is also an object of this invention. Both soluble and inactive mutant forms of PHEX can be used to screen ligands to PHEX. These ligands can also be used as substrates or inhibitors of PHEX. PHEX being phosphaturic, an inhibitor thereof will be used to treat phosphaturia and/or hypophosphatemia. On the opposite, a substrate for PHEX or PHEX itself can be used to treat hyperphosphatemia.

Composition, methods and reagents for the synthesis of a soluble form of human PHEX

The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula: 

Derivatives of succinic and glutaric acids and analogs thereof useful as inhibitors of PHEX

The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula:  useful as inhibitors of PHEX. These derivatives are useful for promoting generation of bone mass and treating or preventing diseases or conditions associated with a phosphate metabolism defect. Methods for preparation and intermediates are also disclosed.

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Outremont, Canada

Philippe Crine