Granted Patent B2

US 9,879,246 · App. 13/761,684 · Granted Jan 30, 2018

Abstract

Claims (10)

1. A method for treating or reducing the risk of developing a thrombotic occlusion in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a proteolytic composition, without adjusting the pH of the proteolytic composition to physiological pH prior to said administering, the composition comprising:

a reversibly inactivated, acidified plasmin, the plasmin being substantially free of a plasminogen activator; and a low buffering capacity buffer; wherein the composition is a pharmaceutically acceptable solution that can be raised to physiological pH by adding no more than about 1 volume of serum to the solution relative to a volume of the solution.

2. The method of claim 1 , wherein the plasmin is Glu-plasmin, Lys-plasmin, midi-plasmin, mini-plasmin, or micro-plasmin.

3. The method of claim 1 , wherein the proteolytic composition has a pH of about 2.5 to about 4.

4. The method of claim 1 , wherein the buffer is acetic acid, citric acid, hydrochloric acid, acetate salts, citrate salts, or combinations thereof at a concentration of about 1 mM to about 100 mM.

5. The method of claim 1 , wherein the proteolytic composition further comprises a stabilizing agent selected from the group consisting of glucose, maltose, mannitol, sorbitol, sucrose, lactose, trehalose, and combinations thereof.

6. The method of claim 1 , wherein the proteolytic composition has a plasmin concentration of between about 0.01 mg/mL to about 50 mg/mL.

7. The method of claim 1 , wherein the therapeutically effective amount of the proteolytic composition provides plasmin in a range of between about 0.1 mg plasmin/kg body weight and 10 mg plasmin/kg body weight.

8. The method of claim 1 , wherein the proteolytic composition is administered locally.

9. The method of claim 1 , wherein the thrombotic occlusion is a vascular occlusion selected from a coronary thrombosis, deep venous thrombosis, peripheral thrombosis, embolic thrombosis, hepatic vein thrombosis, marasmic thrombosis, sinus thrombosis, venous thrombosis, an arterial thrombosis, an occluded arterio-venal shunt, or an occluded catheter device.

Assignments (25)