Ultragenyx Pharmaceutical Inc.

Biomarin Pharmaceutical Inc.

Steven Jungles

Emil D Kakkis

He Zhao

Gabrielle Morris

Jeff Grubb

Michael Vellard

Robert Baffi

Mark Henderson

Victoria Sluzky

Adriano Indolese

Gabriele Roidl

Emil Kaskkis

John Klopp

Christian Müller

Philipp Schmidt

Stefan Kaiser

Christian Mueller

The present invention provides sialic acid analogs and their compositions useful for the treatment of sialic acid deficiencies.

Sialic acid analogs

The present application relates to sialylated glycoprotein compositions and methods of their use in treating various conditions and disorders.

Sialylated glycoprotein compositions and uses thereof

Sialylated glycoprotein compositons and uses thereof

The present disclosure provides a method that efficiently produces (6R)-tetrahydrobiopterin of Formula I in high yield and purity. The method includes the step of hydrolyzing diacetylbiopterin to biopterin under basic conditions in a biphasic mixture comprising an organic phase and an aqueous phase. After substantially complete hydrolysis of diacetylbiopterin, the aqueous phase containing biopterin can be separated from the organic phase containing most of the organic impurities, which avoids the time-consuming step of isolating biopterin as a solid. The aqueous solution containing biopterin is stereoselectively hydrogenated to (6R)-tetrahydrobiopterin under basic conditions and high hydrogen pressure in the presence of a metal catalyst (e.g., a platinum catalyst). To improve the purification of an acid addition salt of (6R)-tetrahydrobiopterin (e.g., (6R)-tetrahydrobiopterin dihydrochloride), any residual salts (e.g., sodium salts) in the aqueous solution after the hydrogenation reaction can be removed by contacting the aqueous solution with an ion (e.g., cation) exchange resin or column. Alternatively, removal of residual salts from the aqueous solution can be omitted if an organic amine (e.g., diethylamine or triethylamine) rather than an inorganic base is used in the hydrolysis and/or hydrogenation reactions. 

Method of synthesizing tetrahydrobiopterin

The present invention is directed to a stable solid formulations of tetrahydrobiopterin, processes for producing them, and treatment methods using such formulations.

Stable tablet formulation

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Novato, CA, United States of America

Steven Jungles