Plasma kallikrein inhibitors and uses thereof for preventing hereditary angioedema attack

Abstract

Provided herein are plasma kallikrein antibodies binding to active plasma kallikrein and methods of using such antibodies in preventing hereditary angioedema attack or reducing the rate of hereditary angioedema attack.

1 .- 41 . (canceled) 
     
     
         42 . An aqueous formulation comprising
 sodium phosphate, citric acid, histidine, sodium chloride, polysorbate 80, and an antibody that binds to the same epitope as DX-2930 or competes against DX-2930 for binding to active plasma kallikrein.   
     
     
         43 . The aqueous formulation of  claim 42 , which has a pH of 6.0. 
     
     
         44 . The aqueous formulation of  claim 42 , which comprises:
 about 30 mM of the sodium phosphate;   about 50 mM of the histidine;   about 90 mM of the sodium chloride; and   about 0.1% of the polysorbate 80.   
     
     
         45 . The aqueous formulation of  claim 42 , wherein the antibody comprises the same heavy chain and light chain complementary determining regions (CDRs) as DX-2930. 
     
     
         46 . The aqueous formulation of  claim 42 , wherein the antibody comprises the same heavy chain variable domain and light chain variable domain as DX-2930. 
     
     
         47 . The aqueous formulation of  claim 42 , wherein the antibody is a full length antibody or an antigen-binding fragment thereof. 
     
     
         48 . The aqueous formulation of  claim 47 , wherein the antibody is an IgG molecule. 
     
     
         49 . The aqueous formulation of  claim 48 , wherein the antibody is an IgG1 molecule. 
     
     
         50 . The formulation of  claim 47 , wherein the antibody is DX-2930. 
     
     
         51 . A method of preventing hereditary angioedema (HAE) attack or reducing the rate of HAE attack, the method comprising administering to a subject in need thereof the aqueous formulation of  claim 42 . 
     
     
         52 . The method of  claim 51 , wherein the subject is a human patient having type I or type II HAE. 
     
     
         53 . The method of  claim 51 , wherein the subject is a human patient experiencing at least two HAE attacks per year prior to the treatment. 
     
     
         54 . The method of  claim 53 , wherein the human patient had at least one HAE attack within 6 months prior to the first administration. 
     
     
         55 . The method of  claim 53 , wherein the human patient had at least 2 HAE attacks within 3 months prior to the first administration. 
     
     
         56 . The method of  claim 55 , wherein the human patient had at least 9 HAE attacks within 3 months prior to the first administration. 
     
     
         57 . The method of  claim 51 , wherein the aqueous formulation is administered to the subject once every two to four weeks. 
     
     
         58 . The method of  claim 57 , wherein the aqueous formulation is administered to the subject every two weeks. 
     
     
         59 . The method of  claim 57 , wherein the aqueous formulation is administered to the subject every four weeks. 
     
     
         60 . The method of  claim 51 , wherein the aqueous formulation is administered subcutaneously. 
     
     
         61 . The method of  claim 51 , wherein the aqueous formulation comprises a dose of the antibody that is 100 to 300 mg. 
     
     
         62 . The method of  claim 61 , wherein the dose of the antibody is 300 mg.