Use of C1 inhibitor for the prevention of ischemia-reperfusion injury

• US 8,415,288 B2
• Filed: 10/11/2011
• Issued: 04/09/2013
• Est. Priority Date: 12/21/2005
• Status: Active Grant

• Current Assignee: Pharming Intellectual Property B.V. (Pharming Group N.V.)
• Original Assignee: Pharming Intellectual Property B.V. (Pharming Group N.V.)
• Inventors: Mannesse, Maurice, Nuijens, Johannes Henricus, Pieper, Frank, De Simoni, Maria Grazia, Ziere, Gijsbertus Johannes
• Primary Examiner(s): Carlson, Karen Cochrane
• Application Number:
  US13/271,107
• Publication Number:
  US 20120088728A1
• Time in Patent Office: 546 Days
• Field of Search: 514/1, 530/350
• US Class Current: 514/1
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to the therapeutic and prophylactic use of C1 inhibitor for preventing, reducing and treating ischemia and reperfusion injury. The C1 inhibitor of the present invention is still therapeutically effective when administered after an ischemic period and reperfusion and therefore particularly useful for unforeseen occurrences of ischemic reperfusion such as e.g. a stroke.

Claims

1. A method of preventing, reducing or treating injury from brain or cerebral ischemia or reperfusion thereof in a patient comprising administering to the patient a C1 inhibitor having a reduced level of terminal sialic acid residues compared to plasma derived human C1 inhibitor and a plasma half-life of less than 6 hours, whereby the C1 inhibitor is administered at least 1 hour after the onset of ischemia and/or at least ten minutes after reperfusion.

2. The method according to claim 1, wherein the C1 inhibitor comprises a glycan that has a terminal residue selected from galactose, N-acetylgalactosamine, N-acetylglucosamine, mannose and fucose.

3. The method according to claim 1, wherein the C1 inhibitor is obtained from a genetically engineered cell or organism.

4. The method according to claim 3, wherein the C1 inhibitor is obtained from a transgenic non-human animal.

5. The method according to claim 4, wherein the C1 inhibitor is obtained from the milk of said transgenic non-human animal.

6. The method according to claim 4, wherein the transgenic non-human animal is a bovine or an animal of the order Lagomorpha, preferably a rabbit.

7. The method according to claim 1, wherein the C1 inhibitor is used in an amount in the range of 50-2000 units per kg body weight.

8. The method according to claim 1, wherein the C1 inhibitor is administered 1-18 hours after the onset of ischemia.

9. The method according to claim 1, wherein the C1 inhibitor is administered in combination with a thrombolytic agent or after treatment with such agent.

10. The method according to claim 1, wherein the patient has at least one unforeseen sudden or acute occurrence of ischemia and/or reperfusion injury.

11. The method according to claim 10, wherein the C1 inhibitor administration prevents, reduces or treats at least one of ischemia and reperfusion injury after stroke or perinatal stroke in the patient.

12. The method according to claim 1, wherein the patient has at least one foreseen occurrence of ischemia and/or reperfusion injury, preferably after organ transplantation.

13. The method of claim 1, wherein the C1 inhibitor is administered at least 3 hours after the onset of ischemia.