Other

Novartis Vaccines & Diagnostics, Gmbh

G.d. Searle LLC

Chiron Corporation

Pharmacia & Upjohn Company

Mark E Gustafson

Glenn J Dorin

Robert F Halenbeck

Kirk William Johnson

Bao-lu Chen

Gary V Johnson

Hassan Madani

Gregory L Pattison

Michael Tsang

Gary S Bild

Bo H Arve

Maninder S Hora

Rajsharan K Rana

Maninder S Hoba

Cynthia A Cowgill

Patricio T Riquelme

Douglas G Bolesch

David H Reifsnyder

Raisharan K Rana

Duane Inlow

Rejsharan K Bana

Highly purified preparations of TFPI or TFPI analogs can be prepared using a method that generally involves the following steps: (1) expression of TFPI or TFPI analog in, (2) isolation of refractile bodies, (3) dissolution of the refractile bodies and refolding of the expressed TFPI or TFPI analog, (4) SP-Sepharose fast flow (FF) chromatography, (5) a first concentration and diafiltration step, (6) Q-Sepharose high (HP) performance chromatography, (7) butyl hydrophobic interaction chromatography (HIC), (8) SP-Sepharose HP chromatography, and (9) a second concentration/diafiltration step. Less than about 12% of the TFPI or TFPI analog molecules in such preparations are modified TFPI or TFPI analog species (i.e., oxidized, carbamylated, acetylated, deamidated, aggregated, or misfolded species).

Method of purifying TFPI and TFPI analogs

Compositions are described that are suitable for formulating TFPI. Solubilizers and stabilizers facilitate the preparation of pharmaceutically acceptable compositions of TFPI at various concentrations.

Formulation, solubilization, purification, and refolding of tissue factor pathway inhibitor

A method of modifying protein solubility employs polyionic polymers. These facilitate the solubilization, formulation, purification and refolding of proteins especially incorrectly folded proteins and aggregated proteins. Compositions are described that are suitable for formulating TFPI. The compositions allow preparation of pharmaceutically acceptable compositions of TFPI at concentrations above 0.2 mg/mL and above 10 mg/mL.

Method of solubilizing, purifying, and refolding protein

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St. Charles, MI, United States of America

Mark E Gustafson