Granted Patent B2

US 12,644,108 · App. 18/169,480 · Granted Jun 2, 2026

Inventors: Christine A. Sheaffer (Doylestown, PA); Michael Berbaum (Pottstown, PA); John Hanna (East Norriton, PA); Jason Dziadosz (Quakertown, PA); Daniel Shanafelt (Red Hill, PA)

Assignee: Endo Operations Limited

C12N9/52C12Y304/24003A61K31/00A61K38/00G01N33/56911

Abstract

Claims (19)

1 . A composition for purification of a collagenase, the composition comprising:

a collagenase derived from Clostridium histolyticum;

a metalloprotease derived from Clostridium histolyticum , wherein the metalloprotease is not a collagenase enzyme;

ammonium sulfate;

a zinc content of less than about 80 ppm; and

a nickel content of less than about 2.0 ppm.

2 . The composition of claim 1 , wherein the collagenase comprises:

a collagenase I enzyme;

a collagenase II enzyme; or

a collagenase I enzyme and a collagenase II enzyme.

3 . The composition of claim 1 , wherein the metalloprotease is an M4 metalloprotease.

4 . The composition of claim 3 , wherein the M4 metalloprotease is a neutral protease.

5 . The composition of claim 1 , wherein the nickel content is less than about 1.2 ppm, less than about 1.0 ppm, less than about 0.9 ppm, less than about 0.8 ppm, less than about 0.7 ppm, less than about 0.6 ppm, less than about 0.5 ppm, less than about 0.4 ppm, less than about 0.3 ppm, less than about 0.2 ppm, less than about 0.1 ppm, less than about 0.09 ppm, less than about 0.08 ppm, less than about 0.07 ppm, less than about 0.06 ppm, less than about 0.05 ppm, less than about 0.04 ppm, less than about 0.03 ppm, less than about 0.02 ppm, or less than about 0.01 ppm.

6 . The composition of claim 1 , wherein the zinc content is less than about 50 ppm, less than about 25 ppm, less than about 10 ppm, less than about 5 ppm, less than about 3 ppm, or less than about 1 ppm.

7 . The composition of claim 1 , further comprising low levels of metals selected from aluminum, arsenic, calcium, cadmium, chromium, copper, iron, magnesium, and lead.

8 . The composition of claim 1 , wherein the ammonium sulfate is present at a concentration of about 0.8 M to about 1.2 M.

9 . The composition of claim 8 , wherein the ammonium sulfate is present at a concentration of about 1 M.

10 . The composition of claim 1 , further comprising a protease inhibitor.

11 . The composition of claim 10 , wherein the protease inhibitor is leupeptin.

Assignments (5)

Continuity (4)

References Cited (400)