Shire Human Genetic Therapies, Inc.

Takeda Pharmaceutical Company Limited

The Ohio State University

Gaozhong Zhu

Zahra Shahrokh

Kris Lowe

Pericles Calias

Jing Pan

Teresa Leah Wright

Vinh Nguyen

James Christian

Richard Pfeifer

Jennifer Terew

Brian Vernaglia

Jamie Tsung

Yuan Jiang

Farah Natoli

Jeffrey Alan Hubbell

Hanne Bentz

Steven Paul Schwendeman

Muthuraman Meiyappan

Jeffrey Scott DePue

Helge Alfred Reisch

Jichao Kang

Anna S Shenderova

Richard Fahmer

Rick Fahrner

Wenlei Jiang

Richard Fahrner

Fritz Blatter

Michael Peter Hahn

Jennifer Robin

The present invention relates generally to the field of pharmaceuticals, and specifically relates to isofagomine (IFG), novel salts thereof and preparation methods and uses of these, for example, in formulating pharmaceutical compositions for the treatment of Gaucher disease. Also provided are novel crystalline forms of isofagomine salts, methods for preparing the crystalline forms, and their use in formulating pharmaceutical compositions.

Isofagomine salts, methods of use and formulations

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Methods and compositions for CNS delivery of heparan N-sulfatase

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

Methods and compositions for CNS delivery of iduronate-2-sulfatase

Methods and compositions for CNS delivery of heparan n-sulfatase

Compositions of proteins having free thiols, and methods of making and using such compositions, are described.

Stabilized compositions of proteins having a free thiol moiety

Stabilized compositions of proteins having a free thiol moeity

Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers

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Weston, MA, United States of America

Gaozhong Zhu