Saint Louis University

Biomarin Pharmaceutical Inc.

Kanazawa University

Shimane University

Zystor Therapeutics, Inc.

William S Sly

Jeffrey H Grubb

Jonathan LeBowitz

Shunji Tomatsu

Stephen M Beverley

Tatsuo Nishioka

Ken-ichi Miyamoto

Seiji Yamaguchi

Adriana Maria Montano Suarez

Shunjl Tomatsu

Monica A Gutierrez

Hirotaka Oikawa

Amelia Ortigoza Rodriguez, Legal Representative

Transplacental enzyme replacement therapy (ERT) is disclosed for deficiency of a polypeptide such as a tissue-nonspecific alkaline phosphatase (TNSALP) by administering a pharmaceutical composition that comprises a water-soluble TNSALP portion, e.g., C-terminus-truncated TNSALP peptide-bonded to an IgG1 antibody Fc portion, to a pregnant animal whose fetus or embryo is in need of such therapy. Also contemplated is a method for treating a metabolic disorder, such as HPP, in a fetus or embryo where a fusion protein that comprises a Fc fragment of an IgG1 antibody peptide-bonded to TNSALP is administered to a pregnant mother. The protein crosses the placenta of the mother and enters the fetal blood stream. The protein is taken up into fetal tissue such that the TNSALP restores normal metabolic activity in the fetus.

Prenatal enzyme replacement therapy for hypophosphatasia

The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.

Compositions and methods for treating hypophosphatasia

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Targeted therapeutic proteins

The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human &#x3b2;-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.

Enhancing the effect of therapeutic proteins on the central nervous system

The invention is directed to chimeral fusion proteins having an IgG1 antibody Fc portion and a lysosomal storage enzyme, particularly a Fc-GUS fusion protein useful in treating Sly's disease in an embryo or fetus. The invention is also directed to methods of treating in born errors of metabolism, particularly Sly's disease, in a fetus by delivering to a pregnant mother a Fc-MPS emzyme fusion protein.

Chimeral polypeptide composition for cross-placenta delivery

Growing community of inventors

St. Louis, MO, United States of America

William S Sly