Anti-il4-il 13 bispecific antibodies

Abstract

Disclosed herein are safe doses of dual-V-region antibody-like binding proteins or fragments thereof, as well as methods for assessing binding of dual-V-region antibody-like proteins or fragments thereof to their targets, and methods of treating idiopathic pulmonary fibrosis (IPF) by administering safe doses of dual-V-region antibody-like binding proteins or fragments thereof. In some embodiments, the dual-V-region antibody-like binding proteins or fragments thereof bind both IL-4 and IL-13.

1 . A safe dose in a human subject of a dual-V-region antibody-like protein or a fragment thereof that specifically binds to IL-4 and IL-13, wherein the dose comprises up to about 200 mg of the antibody-like protein or fragment thereof. 
     
     
         2 . The safe dose of  claim 1 , wherein the dose comprises about 200 mg of the antibody-like protein or fragment thereof. 
     
     
         3 . The safe dose of  claim 1 , wherein the dose comprises about 100 mg of the antibody-like protein or fragment thereof. 
     
     
         4 . The safe dose of  claim 1 , wherein the dose comprises about 50 mg of the antibody-like protein or fragment thereof. 
     
     
         5 . The safe dose of any of  claims 1 - 4 , wherein the human subject has idiopathic pulmonary fibrosis (IPF). 
     
     
         6 . A method of determining whether a dose comprising a dual-V-region antibody-like protein or a fragment thereof administered to a human subject specifically binds to IL-4 or IL-13 within the human subject, the method comprising:
 (a) administering the dose to the human subject;   (b) measuring the amount of TARC/CCL17 protein in a blood, plasma, or serum sample drawn from the human subject, wherein a decrease in the amount of TARC/CCL17 in the blood sample relative to an amount of TARC/CCL17 in the subject measured before the dose was administered signifies binding of the dual-V-region antibody-like protein or fragment thereof to IL-4 or IL-13; and   (c) increasing or decreasing the dose depending on the decrease in TARC/CCL17 measured in step (b).   
     
     
         7 . The method of  claim 6 , wherein step (c) further comprises increasing the dose if the decrease in TARC/CCL17 measured in step (b) is below a threshold value, or decreasing the dose if the decrease in TARC/CCL17 measured in step (b) is above a threshold value. 
     
     
         8 . The method of  claim 7 , wherein the threshold value is about a 43% decrease in the amount of TARC/CCL17 relative to the amount of TARC/CCL17 in the subject measured before the dose was administered. 
     
     
         9 . The method of any of  claims 6 - 8 , wherein the dose is administered subcutaneously. 
     
     
         10 . The method of any of  claims 6 - 9 , wherein the amount of TARC/CCL17 is detected by enzyme-linked immunosorbent assay (ELISA). 
     
     
         11 . The method of any of  claims 6 - 10 , wherein the human subject has idiopathic pulmonary fibrosis (IPF). 
     
     
         12 . A protein biomarker for binding of an antibody or antibody-like binding protein to IL-4 or IL-13 or both in a human subject, wherein the biomarker is TARC/CCL17. 
     
     
         13 . The protein biomarker of  claim 12 , wherein the antibody or antibody-like binding protein is a dual-V-region antibody-like binding protein. 
     
     
         14 . The protein biomarker of  claim 12  or  13 , wherein the human subject has idiopathic pulmonary fibrosis (IPF). 
     
     
         15 . A method of treating idiopathic pulmonary fibrosis (IPF), comprising administering to a human subject with IPF up to 200 mg of a dual-V-region antibody-like binding protein or a fragment thereof. 
     
     
         16 . The method of  claim 15 , wherein the dual-V-region antibody-like binding protein or fragment thereof binds IL-4, IL-13, or both. 
     
     
         17 . The method of  claim 15  or  16 , wherein the dual-V-region antibody-like binding protein or fragment thereof is administered once per week.