Plasma kallikrein inhibitors and uses thereof for treating hereditary angioedema attack

Abstract

Provided herein are methods of treating and preventing hereditary angioedema attack in certain human patient subpopulations whose disease is well controlled in a first treatment period, which involves the use of an antibody that binds human plasma kallikrein. Such patients can be subject to a reduced dosage of the antibody and/or a prolonged dosing interval in a second treatment period.

1 . A method for treating hereditary angioedema (HAE) attack or reducing the rate of HAE attack, the method comprising:
 administering to a subject in need thereof an antibody that binds human plasma kallikrein at about 300 mg every about two weeks in a first treatment period, which is about 4-9 months;   monitoring the subject for HAE attack during the first treatment period; and   reducing the dosage of the antibody to about 300 mg every about 4 weeks in the subject, who is free of HAE attack in the first treatment period;   
       wherein the antibody comprises:
 a heavy chain complementarity determining region (HCDR) 1 set forth as HYIMM (SEQ ID NO: 5); 
 a HCDR2 set forth as GIYSSGGITVYADSVKG (SEQ ID NO: 6); 
 a HCDR3 set forth as RRIGVPRRDEFDI (SEQ ID NO: 7); 
 a light chain complementarity determining region (LCDR) 1 set forth as RASQSISSWLA (SEQ ID NO: 8); 
 a LCDR2 set forth as KASTLES (SEQ ID NO: 9); and 
 a LCDR3 set forth as QQYNTYWT (SEQ ID NO: 10). 
 
     
     
         2 . The method of  claim 1 , wherein the first treatment period is about 6 months. 
     
     
         3 . The method of  claim 1 , wherein the patient has a low body weight. 
     
     
         4 . The method of  claim 3 , wherein the patient has a body weight of less than 35 kg. 
     
     
         5 . The method of  claim 1 , wherein the patient is a pediatric patient. 
     
     
         6 . The method of  claim 1 , wherein the antibody comprises a heavy chain immunoglobulin variable domain (V H ) of SEQ ID NO: 3 and a light chain immunoglobulin variable domain (VL) of SEQ ID NO: 4. 
     
     
         7 . The method of  claim 1 , wherein the antibody is a full length antibody or an antigen-binding fragment thereof. 
     
     
         8 . The method of  claim 1 , wherein the antibody is an IgG1 molecule. 
     
     
         9 . The method of  claim 8 , wherein the antibody comprises a heavy chain of SEQ ID NO:1 and a light chain of SEQ ID NO:2. 
     
     
         10 . The method of  claim 1 , wherein the antibody is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier. 
     
     
         11 . The method of  claim 10 , wherein the pharmaceutical composition comprises sodium phosphate, citric acid, histidine, sodium chloride, and polysorbate 80. 
     
     
         12 . The method of  claim 11 , wherein the sodium phosphate is at a concentration of about 30 mM, the citric acid is at a concentration of about 19 mM, the histidine is at a concentration of about 50 mM, the sodium chloride is at a concentration of about 90 mM, and the polysorbate 80 is at about 0.01%. 
     
     
         13 . The method of  claim 1 , wherein the antibody is administered subcutaneously. 
     
     
         14 . The method of  claim 1 , wherein the subject is a human patient having, suspected of having, or at risk for HAE. 
     
     
         15 . The method of  claim 14 , wherein the subject has HAE type I or type II.