Anti-FSTL3 Antibodies And Uses Thereof

Abstract

The present invention provides antibodies and antigen binding fragments thereof that bind to human Follistatin-Like-3 (FSTL3) protein, compositions comprising such antibodies, and methods of making and using such antibodies.

What is claimed is: 
     
         1 . A method of reducing insulin resistance in a subject in need thereof, comprising administering to the subject an effective amount of an antibody, or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment binds to a human follistatin-like 3 (FSTL3) protein and comprises:
 (i) an antibody heavy chain variable (V H ) domain comprising:
 a) a complementarity determining region 1 (CDR1) comprising SEQ ID NO:3; 
 b) a complementarity determining region 2 (CDR2) comprising SEQ ID NO:4; and 
 c) a complementarity determining region 3 (CDR3) comprising SEQ ID NO:5; and 
   (ii) an antibody variable light chain (V L ) domain comprising:
 a) a CDR1 comprising SEQ ID NO:8; 
 b) a CDR2 comprising SEQ ID NO:9; and 
 c) a CDR3 comprising SEQ ID NO:10. 
   
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an antibody heavy chain variable (V H ) domain comprising SEQ ID NO:2. 
     
     
         3 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an antibody variable light chain (V L ) domain comprising SEQ ID NO:7. 
     
     
         4 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an antibody V H  domain comprising SEQ ID NO:2 and an antibody V L  domain comprising SEQ ID NO:7. 
     
     
         5 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof is humanized. 
     
     
         6 . The method of  claim 1 , wherein the antigen-binding fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, a Fv, a scFv, a dsFv, a minibody and a diabody. 
     
     
         7 . The method of  claim 1 , comprising administering to the subject a composition comprising the antibody or antigen-binding fragment thereof and a pharmaceutically-acceptable carrier. 
     
     
         8 . The method of  claim 1 , comprising administering to the subject the antibody or antigen-binding fragment thereof and at least one additional therapeutic agent. 
     
     
         9 . The method of  claim 8 , wherein the least one additional therapeutic agent is insulin. 
     
     
         10 . The method of  claim 8 , wherein the least one additional therapeutic agent is a myostatin inhibitor, an activin inhibitor, or a combination thereof. 
     
     
         11 . The method of  claim 1 , wherein the subject has one or more disorders selected from the group consisting of type 1 diabetes, type 2 diabetes, hypoglycemia, hyperglycemia, secretory dysfunction, loss of pancreatic β-cell function, and loss of pancreatic β-cells. 
     
     
         12 . The method of  claim 1 , wherein the subject has type 1 diabetes. 
     
     
         13 . The method of  claim 1 , wherein the subject has type 2 diabetes. 
     
     
         14 . The method of  claim 1 , wherein the subject is pre-diabetic. 
     
     
         15 . The method of  claim 1 , wherein the subject is a human. 
     
     
         16 . The method of  claim 1 , wherein insulin secretion from beta cells is increased in the subject following administration of the antibody or antigen-binding fragment thereof. 
     
     
         17 . The method of  claim 1 , wherein beta cell regeneration is increased in the subject following administration of the antibody or antigen-binding fragment thereof. 
     
     
         18 . The method of  claim 1 , wherein transdifferentiation of an alpha cell or other pancreatic cell to a beta cell is enhanced in the subject following administration of the antibody or antigen-binding fragment thereof. 
     
     
         19 . The method of  claim 1 , wherein transdifferentiation of a beta cell to an alpha cell or other pancreatic cell is inhibited in the subject following administration of the antibody or antigen-binding fragment thereof.