Use of il-1 beta binding antibodies for treating peripheral arterial disease

Abstract

The present invention relates to a method for treating or alleviating the symptoms of peripheral arterial disease (PAD) in a subject, comprising administering about 25 mg to about 300 mg of an IL-1β binding antibody or functional fragment thereof.

1 . A method for treating or alleviating the symptoms of peripheral arterial disease (PAD) in a patient, comprising administering a therapeutically effective amount of an antibody or antigen binding fragment thereof that binds to IL-1β to a patient in need thereof, wherein said antibody or antigen binding fragment thereof comprises:
 i) an immunoglobulin V H  domain comprising the amino acid sequence set forth as SEQ ID NO:1 and an immunoglobulin V L  domain comprising the amino acid sequence set forth as SEQ ID NO:2; 
 ii) an immunoglobulin V H  domain comprising, in sequence, a complementarity determining region (CDR) 1 comprising the amino acid sequence set forth as SEQ ID NO:3, a CDR2 comprising the amino acid sequence set forth as SEQ ID NO:4, and a CDR3 comprising the amino acid sequence set forth as SEQ ID NO:5, and an immunoglobulin V L  domain comprising, in sequence, a CDR1 comprising the amino acid sequence set forth as SEQ ID NO:6, a CDR2 comprising the amino acid sequence set forth as SEQ ID NO:7 and a CDR3 comprising the amino acid sequence set forth as SEQ ID NO:8. 
 
     
     
         2 . The method according to  claim 1 , wherein the antibody or antigen binding fragment is capable of inhibiting the binding of IL-1β to its receptor and has a K D  for binding to IL-1β of about 50 pM or less. 
     
     
         3 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is a Fab, Fab′, F(ab′) 2 , Fv, or a single chain Fv. 
     
     
         4 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is a human or humanized monoclonal antibody. 
     
     
         5 . The method according to  claim 1 , wherein the antibody or antigen binding fragment is canakinumab. 
     
     
         6 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient at a dose of about 50 mg or about 80 mg or about 150 mg or about 300 mg. 
     
     
         7 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient intravenously. 
     
     
         8 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is administered to the patient subcutaneously. 
     
     
         9 . The method according to  claim 1 , wherein the antibody or antigen binding fragment is administered every 2 weeks, twice a month, monthly, every 6 weeks, every 2 months, every 3 months, every 4 months, every 5 months, or every 6 months from the first administration. 
     
     
         10 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is comprised in a lyophilized pharmaceutical formulation. 
     
     
         11 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is comprised in a liquid pharmaceutical formulation. 
     
     
         12 . The method according to  claim 1 , wherein the formulation is disposed within a pre-filled syringe, vial, or autoinjector. 
     
     
         13 . The method according to  claim 1 , wherein the antibody or antigen binding fragment thereof is comprised in a dosage unit form suitable for intravenous administration. 
     
     
         14 . The method according to  claim 1 , wherein said patient is concomitantly receiving a beta-adrenergic blocking drug, a statin, an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker. 
     
     
         15 . The method according to  claim 1 , wherein the subject is exhibiting an ankle-brachial index between 0.5 and 0.85 in at least one leg before treatment. 
     
     
         16 . The method according to  claim 1 , wherein the subject has improved vascular structure and function after 3 months of treatment. 
     
     
         17 . The method according to  claim 1 , wherein reduced plaque burden in the peripheral artery walls of said subject is observed after at least 3 months of treatment. 
     
     
         18 . The method according to  claim 1 , wherein a reduced plaque burden compared to before treatment in said subject is determined in the superficial femoral artery after at least 3 months of treatment. 
     
     
         19 . The method according to  claim 1 , wherein a reduced plaque burden compared to before treatment in said subject is determined in the superficial femoral artery after at least 12 months of treatment. 
     
     
         20 . The method according to  claim 5 , wherein canakinumab is administered in a liquid formulation comprising 10-200 mg/ml canakinumab, mannitol, histidine and polysorbate 80, wherein the pH of the formulation is 6.1-6.9.