The Immune Response Corporation

Rhone-poulenc Rorer Pharmaceuticals Inc.

Centeon L.l.c.

Christopher P Prior

Michael E Hrinda

Ted C Lee

David L Farb

David M Weber

Richard S Gore

James J Harter

Jonathan J Mitschelen

George C Tarr

Pierre M Bay

Thomas W Irish

David Weber

This invention is directed to a continuous process for producing viral particles comprising providing in a perfused growth medium a population of viable virally infected non-lytic cells, and removing medium containing said cells at a rate to maintain the steady-state log-phase growth of cells remaining in said perfused growth medium. The invention is also directed to a process for purifying retroviral particles comprising passing a solution comprising the retroviral particles and contaminants through an anion exchange resin, and eluting the retroviral particles from the resin.

Highly efficient production and isolation of viral particles utilizing

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

This invention is directed to a continuous process for producing viral particles by providing in a perfused growth medium a population of viable virally infected non-lytic cells, and removing medium containing said cells at a rate to maintain the steady-state log-phase growth of cells remaining in the perfused growth medium. The invention is also directed to a process for purifying retroviral particles by passing a solution comprising the retroviral particles and contaminants through an anion exchange resin, and eluting the retroviral particles from the resin. The preferred exchange resin is a tentacle anion exchange resin.

Production and purification of retroviral particles using tentacle anion

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.

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Wayne, PA, United States of America

Christopher P Prior