Method of treating atherosclerosis

Abstract

The present disclosure relates to a method of treating or preventing atherosclerosis in a subject by administering an inhibitor of FXII.

1 . A method of treating atherosclerosis in a subject, comprising administering to the subject an effective amount of an anti-Factor XII (FXII) antibody or antigen binding fragment thereof comprising:
 (i) a V H  comprising:
 (a) a sequence set forth in SEQ ID NO: 6; or 
 (b) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 10; and a CDR3 comprising a sequence set forth in SEQ ID NO: 12; or 
 (c) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 9; and a CDR3 comprising a sequence set forth in SEQ ID NO: 11; and/or 
   (ii) a V L  comprising:
 (a) a sequence set forth in SEQ ID NO: 7; or 
 (b) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 16; or 
 (c) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 15. 
   
     
     
         2 . The method of  claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof comprises:
 (i) a V H  comprising a sequence set forth in SEQ ID NO: 18 and a V L  comprising a sequence set forth in SEQ ID NO: 19 or   (ii) a heavy chain comprising a sequence set forth in SEQ ID NO: 20 and a light chain comprising a sequence set forth in SEQ ID NO: 21.   
     
     
         3 . The method of  claim 1 , wherein the anti-FXII antibody is an IgG antibody. 
     
     
         4 . The method of  claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is linked to a fusion partner, wherein the fusion partner comprises polyethylene glycol (PEG) or a half-life enhancing polypeptide, wherein the half-life enhancing polypeptide is selected from the group consisting of albumin, afamin, alpha-fetoprotein, vitamin D binding protein, human albumin, an immunoglobulin, and an Fc of an IgG. 
     
     
         5 . The method of  claim 4 , wherein the half-life enhancing polypeptide is linked to the anti-FXII antibody or antigen binding fragment thereof 4via a linker. 
     
     
         6 . The method of  claim 5 , wherein the anti-FXII antibody or antigen binding fragment thereof is a fusion protein comprising human albumin linked to the anti-FXII antibody or antigen binding fragment thereof via a linker peptide. 
     
     
         7 . The method of  claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is administered to the subject intravenously or subcutaneously or intrathecally. 
     
     
         8 . The method of  claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is administered to the subject:
 (i) in a single dose; or   (ii) in a plurality of doses; or   (iii) as a continuous dose.   
     
     
         9 . The method of  claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is administered to the subject at a concentration from about 0.01 to about 100 mg/kg body weight. 
     
     
         10 . The method of  claim 1 , wherein the subject is at risk of developing atherosclerosis and/or suffers from diabetes and/or obesity. 
     
     
         11 . A kit for use in the treatment or prevention of atherosclerosis in a subject, comprising:
 (a) an anti-FXII antibody or antigen binding fragment thereof comprising
 (i) a V H  comprising:
 (A) a sequence set forth in SEQ ID NO: 6; or 
 (B) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 10; and a CDR3 comprising a sequence set forth in SEQ ID NO: 12; or 
 (C) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 9; and a CDR3 comprising a sequence set forth in SEQ ID NO: 11; and/or 
 
 (ii) a V L  comprising:
 (A) a sequence set forth in SEQ ID NO: 7; or 
 (B) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 16; or 
 (c) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 15; 
 
   (b) instructions for using the kit in treating or preventing atherosclerosis in the subject; and   (c) optionally, at least one further therapeutically active compound or drug.   
     
     
         12 . An anti-Factor XII (FXII) antibody or antigen binding fragment thereof, wherein the anti-FXII antibody comprises:
 (i) a V H  comprising a sequence set forth in SEQ ID NO: 18 and a V L  comprising a sequence set forth in SEQ ID NO: 19; or   (ii) a heavy chain comprising a sequence set forth in SEQ ID NO: 20 and a light chain comprising a sequence set forth in SEQ ID NO: 21.