Purification of collagenases from clostridium histolyticum...

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Separation or purification

Reexamination Certificate

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C435S023000, C435S219000, C435S220000

Reexamination Certificate

active

07956167

ABSTRACT:
The present invention provides a method for purifyingClostridium histolyticumcollagenase type I and type II proteins from a complex mixture by subsequently performing a precipitation with ammonium sulfate, hydrophobic interaction chromatography, cation exchange chromatography, and anion chromatography. Conditions are provided which lead to a stabilized, partially purified preparation even after the precipitation step. The method of the invention leads to a quick and efficient removal of other proteolytic activities. The preparations according to the invention provide exceptionally pure and intact collagenase type I and type II proteins which are enzymatically active. The invention also provides blends of the two isolated proteins. The invention further provides the use of the purified collagenase proteins or blends thereof for treating a tissue sample in vitro.

REFERENCES:
patent: 5753485 (1998-05-01), Dwulet et al.
patent: 0468411 (1995-11-01), None
patent: 98/22574 (1995-05-01), None
patent: 03/004628 (2003-01-01), None
Antonioli, B. et al., “Characterization of Collagenase Blend Enzymes for Human Islet Transplantation,” Tranplantation 84:12 (Dec. 27, 2007) 1568-1575.
Barnett, M. et al., “Quantitative Assessment of Collagenase Blends for Human Islet Isolation,” Transplantation 80:6 (Sep. 27, 2005) 723-728.
Bond, M. et al., “Characterization of the Individual Collagenases fromClostridium histolyticum,” Biochemistry 23 (1984) 3085-3091.
Bond, M. et al., “Purification and Separation of Individual Collagenases ofClostridium histolyticumUsing Red Dye Ligand Chromatography,” Biochemistry 3 (1984) 3077-3085.
Bucher, P. et al., “Assessment of a Novel Two-Component Enzyme Preparation for Human Islet Isolation and Transplantation,” Transplantation 79:1 (Jan. 15, 2005) 91-97.

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