Rhone-poulenc Rorer Pharmaceuticals Inc.

Rorer Pharmaceutical Corporation

Centeon L.l.c.

Ted C Lee

Michael E Hrinda

David L Farb

Christopher P Prior

David Weber

Processes for preparing aqueous solutions of cysteine-altered von Willebrand Factor fragment which are substantially free of aggregate and capable of therapeutic use for treating thrombosis are provided. The claimed process comprises providing an aqueous solution of vWF fragment and denaturant and containing undesired contaminants, said solution having an acidic pH; separating said contaminants from said solution by contacting said solution with an affinity chromatography medium to which said vWF fragments adhere; eluting said vWF fragment from said affinity chromatography medium in the presence of the denaturant; and separating the eluted fragment from said denaturant while maintaining the aqueous solution of the fragment at a pH of about 2.5 to less than about 5.5 to increase monomerization of, and decrease aggregation of, said fragment, thereby forming an aqueous solution of vWF fragment which is substantially free of aggregate.

Therapeutic fragments of von Willebrand factor

Stable, highly purified Factor VIII protein formulations are provided in high ionic strength media which comprises: sodium chloride, potassium chloride or mixtures thereof; calcium chloride; and histidine as the buffering agent.

Factor VIII formulations in high ionic strength media

An aqueous solution of cysteine-altered von Willebrand Factor fragment which is substantially free of aggregate and capable of therapeutic use for treating thrombosis and a process for preparing such a solution comprising: (A) providing an aqueous solution of the fragment and denaturant; (B) purifying the solution of fragment and denaturant under conditions which promote conversion of aggregated forms of the fragment to the dimeric and/or monomeric forms thereof to provide purified fragment; (C) separating the dissolved, purified fragment from the denaturant while maintaining the aqueous solution of the fragment at a pH of about 2.5 to less than about 5.5 to increase monomerization of, and decrease aggregation of, said purified fragment, thereby forming an aqueous solution of fragment which is substantially free of aggregate.

Disclosed is a method of recovery of antihemophilic factor (AHF) from human plasma by precipitation with citric acid, sodium citrate, or potassium citrate.

High recovery process for antihemophilic factor

Stable factor VIII and other plasma protein formulations are provided in low ionic strength media which comprises: sodium chloride, potassium chloride or mixtures thereof; lysine hydrochloride; and histidine as the buffering agent.

Growing community of inventors

Lansdale, PA, United States of America

Ted C Lee