Fgf21 mimetic antibodies and uses thereof

Abstract

The present disclosure relates to monoclonal antibodies and antigen-binding fragments thereof that bind to human β-klotho, and pharmaceutical compositions and methods of treatment comprising the same.

1 .- 25 . (canceled) 
     
     
         26 . A method of treating a metabolic disorder comprising administering to a subject afflicted with the metabolic disorder an effective amount of an antibody that binds to β-klotho, or antigen-binding fragment thereof, comprising a variable heavy chain as set forth in SEQ ID NO: 15, and a variable light chain as set forth in SEQ ID NO: 26 or 32. 
     
     
         27 . The method of  claim 26 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain as set forth in SEQ ID NO: 15 and a variable light chain as set forth in SEQ ID NO: 26. 
     
     
         28 . The method of  claim 26 , wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain as set forth in SEQ ID NO: 15 and a variable light chain as set forth in SEQ ID NO: 32. 
     
     
         29 . The method of  claim 26 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 17 and a light chain as set forth in SEQ ID NO: 28 or 34. 
     
     
         30 . The method of  claim 26 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 17 and a light chain as set forth in SEQ ID NO: 28. 
     
     
         31 . The method of  claim 26 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 17 and a light chain as set forth in SEQ ID NO: 34. 
     
     
         32 . The method of  claim 26 , wherein the subject is afflicted with one of more of the following: obesity, type 1 diabetes mellitus, pancreatitis, dyslipidemia, hypertriglyceridemia, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, and metabolic syndrome. 
     
     
         33 . The method of  claim 32 , wherein the subject is afflicted with one or more of the following: obesity, diabetes, hypertriglyceridemia, and dyslipidemia. 
     
     
         34 . The method of  claim 32 , wherein the subject is afflicted with NASH. 
     
     
         35 . The method of  claim 32 , wherein the subject is afflicted with NAFLD.