Amicus Therapeutics, Inc.

Hung V Do

Russell Gotschall

John R Flanagan

Elfrida Benjamin

Brandon Alan Wustman

Xiaoyang Wu

Richie Khanna

Ce Feng Liu

Sergey Tesler

Hing Char

Enrique Diloné

Wendy Sunderland

Steven Tuske

Yi Lun

Enrique DilonÉ

John Flanagan

Brandon Wustman

A method for treating Pompe disease including administration of recombinant human acid α-glucosidase having optimal glycosylation with mannose-6-phosphate residues in combination with an amount of miglustat effective to maximize tissue uptake of recombinant human acid α-glucosidase while minimizing inhibition of the enzymatic activity of the recombinant human acid α-glucosidase is provided.

Augmented acid alpha-glucosidase for the treatment of Pompe disease

Provided are a recombinant acid α-glucosidase and pharmaceutical composition comprising a recombinant acid α-glucosidase, wherein the recombinant acid α-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa. Also provided herein are methods of producing, purifying, and formulating the recombinant acid α-glucosidase or pharmaceutical composition for administration to a subject and methods of treating a disease or disorder such as Pompe disease using the recombinant acid α-glucosidase or pharmaceutical composition.

Recombinant human acid alpha-glucosidase

Provided herein are polypeptides comprising one or more non-native cysteine residues that form a disulfide bridge between non-native cysteines within the protein or between non-native cysteines of two monomers of the protein. Such modified human polypeptides are useful in treatment of genetic diseases via enzyme replacement therapy and/or gene therapy.

Disulfide bond stabilized polypeptide compositions and methods of use

Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.

Highly potent acid alpha-glucosidase with enhanced carbohydrates

Provided are pharmaceutical formulations comprising a recombinant acid &#x3b1;-glucosidase, wherein the recombinant acid &#x3b1;-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa; at least one buffer selected from the group consisting of a citrate, a phosphate and combinations thereof; and at least one excipient selected from the group consisting of mannitol, polysorbate 80, and combinations thereof, wherein the formulation has a pH of from about 5.0 to about 7.0. Also provided are methods of treating Pompe disease using these pharmaceutical formulations.

Formulations comprising recombinant acid alpha-glucosidase

Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.

Gene therapy constructs and methods of use

Methods for the production, capturing and purification of recombinant human lysosomal proteins are described. Such recombinant human lysosomal proteins can have high content of mannose-6-phosphate residues. Also described are pharmaceutical compositions comprising such recombinant human lysosomal proteins, as well as methods of treatment and uses of such recombinant human lysosomal proteins.

Method for selection of high M6P recombinant proteins

A method for treating Pompe disease including administration of recombinant human acid &#x3b1;-glucosidase having optimal glycosylation with mannose-6-phosphate residues in combination with an amount of miglustat effective to maximize tissue uptake of recombinant human acid &#x3b1;-glucosidase while minimizing inhibition of the enzymatic activity of the recombinant human acid &#x3b1;-glucosidase is provided.

The present invention provides methods to determine whether a patient with a lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining &#x3b1;-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of &#x3b1;-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.

Method to predict response to pharmacological chaperone treatment of diseases

Disclosed herein are methods of chemical conjugation comprising contacting a lysosomal enzyme with a first crosslinking agent to introduce aldehyde groups; contacting a lysosomal targeting peptide with a second crosslinking agent to introduce a hydrazide group at the N-terminal residue; contacting the lysosomal enzyme with aldehyde groups of step a. with the lysosomal targeting peptide with a hydrazide group at the N-terminal residue of step b; and forming a lysosomal enzyme-lysosomal targeting peptide conjugate.

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New Hope, PA, United States of America

Hung V Do