Treatment and prevention of remote ischemia-reperfusion injury

Patent metadata

Field	Value
Publication number	US-10973891-B2
Application number	US-201916359598-A
Country	US
Kind code	B2
Filing date	Mar 20, 2019
Priority date	Mar 8, 2013
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

The present invention relates to a contact activation system inhibitor, preferably a C1INH, for use in the treatment and/or prevention of remote ischemia-reperfusion injury (IRI), comprising administering the contact activation system inhibitory to an individual.

First claim

The invention claimed is:

1. A method of ameliorating and/or reducing remote ischemia-reperfusion injury (IRI), comprising administering an effective dose of a Factor XII (FXII) inhibitor to an individual in need thereof,
wherein the FXII inhibitor is an antibody.

2. The method according to claim 1 , wherein the antibody is administered parenterally to the individual.

3. The method according to claim 2 , wherein the antibody is administered intravenously, intraarterially, or subcutaneously to the individual.

4. The method according to claim 1 , wherein the antibody is administered to the individual at a dose ranging from 0.01 to 50 mg/kg body weight.

5. The method according to claim 1 , wherein the individual is a patient and the antibody is administered before, during, and/or after a surgical intervention involving reperfusion.

6. The method according to claim 5 , wherein the antibody is administered to the patient up to 6 hours before the surgical intervention or the start of reperfusion.

7. The method according to claim 5 , wherein the antibody is administered to the patient within 72 hours after termination of the surgical intervention or the start of reperfusion.

8. The method according to claim 5 , wherein the surgical intervention is chosen from the group consisting of (a) elective surgery, reconstructive surgery, vascular surgery, cardiac surgery, trauma surgery, crash or crush surgery, cancer surgery, orthopedic surgery, transplantation, and minimally invasive surgery, or
the group consisting of (b) surgical intervention following onset of an initial thrombotic or thromboembolic or another ischemia-inducing disorder, insertion of a device for delivery of one or more pharmacologically active substances, insertion of a device for mechanical removal of complete or partial obstructions, and injection of pharmaceutically active substances.

9. The method according to claim 1 , wherein the reperfusion happens spontaneously or through intervention other than a surgical intervention.

10. The method of claim 1 , wherein the remote ischemia-reperfusion injury (IRI) affects one or more organs or tissues.

11. The method of claim 10 , wherein the one or more organs or tissues is chosen from lung, heart, brain, kidney, intestine, pancreas, liver, extremities, and limbs.

12. The method of claim 1 , wherein the remote ischemia-reperfusion injury (IRI) would lead to multiorgan dysfunction syndrome or systemic inflammatory response syndrome in the absence of treatment.

13. The method of claim 1 , wherein the antibody is an anti-FXIIa monoclonal antibody.

14. The method of claim 13 , wherein the anti-FXIIa monoclonal antibody comprises:
a) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 9, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 13; and
b) a light chain variable region comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 14 or SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 15, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 17.

15. The method of claim 1 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.

16. A method of ameliorating and/or reducing ischemia-reperfusion injury (IRI) in a patient that is to undergo a surgical intervention, comprising administering to the patient an effective dose of a Factor XII (FXII) inhibitor prior to and/or during and/or after the surgical intervention or prior to and/or after start of reperfusion, wherein the ischemia-reperfusion injury (IRI) affects an organ or tissue remote from the site of surgery, wherein the FXII inhibitor is an antibody.

17. The method of claim 16 , wherein the remote ischemia-reperfusion injury (IRI) affects one or more organs or tissues chosen from lung, heart, brain, kidney, intestine, pancreas, liver, extremities, and limbs.

18. The method of claim 16 , wherein the remote ischemia-reperfusion injury (IRI) would lead to multiorgan dysfunction syndrome or systemic inflammatory response syndrome in the absence of treatment.

19. The method of claim 16 , wherein the antibody is an anti-FXIIa monoclonal antibody.

20. The method of claim 19 , wherein the anti-FXIIa monoclonal antibody comprises:
a) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 9, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 13; and
b) a light chain variable region comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 14 or SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 15, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 17.

21. The method of claim 16 , wherein the antibody is a monoclonal anti-FXII antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.

Assignees

• Csl Behring Gmbh
• Univ Bern

Inventors

• Spirig Rolf
• Miescher Sylvia
• Nolte Marc
• Duehrkop-Sisewitsch Claudia
• Rieben Robert

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61K38/36

  Blood coagulation or fibrinolysis factors · CPC title

• C07K14/745

  Blood coagulation or fibrinolysis factors · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P13/12

  of the kidneys · CPC title