Fn14 Binding Proteins and Uses Thereof

Abstract

The present disclosure provides proteins comprising antibody antigen binding domains that bind to Fn14 and uses thereof. The present disclosure also provides methods for treating wasting disorders, such as cachexia.

1 .- 11 . (canceled) 
     
     
         12 . A method of treating or preventing a wasting disorder which is associated with a condition, the method comprising administering to a subject an Fn14-binding protein comprising an antigen binding domain of an anti-Fn14 antibody. 
     
     
         13 . The method of  claim 12 , wherein the wasting disorder is cachexia. 
     
     
         14 . The method of  claim 13 , wherein the wasting disorder is cachexia associated with cancer or diabetes. 
     
     
         15 . The method of  claim 12 , wherein the condition is cancer cachexia and the method additionally comprises selecting a subject suffering from cancer cachexia, wherein the subject suffers from a cancer expressing Fn14. 
     
     
         16 . The method of  claim 12 , wherein the Fn14-binding protein comprises an antigen binding domain of an anti-Fn14 antibody, wherein the antigen binding domain binds specifically to Fn14 and wherein the protein reduces Tweak-induced NFκB-signaling in a cell expressing Fn14, and wherein the protein does not detectably induce NFκB-signaling when contacted to a cell expressing Fn14 in the absence of Tweak. 
     
     
         17 . The method of  claim 12 , wherein the Fn14-binding protein has one or more of the following characteristics:
 (i) binds to recombinant human Fn14 with a K D  of 1 nM or less;   (ii) binds to recombinant human Fn14 with a Kd of about 8×10 −4 s −1  or less;   (iii) binds to an extracellular domain of Fn14 comprising a proline or alanine substituted for the arginine at position 56 of SEQ ID NO: 1 at a similar or substantially the same level as it binds to an extracellular domain of Fn14;   (iv) binds to an extracellular domain of Fn14 comprising an alanine substituted for the arginine at position 58 of SEQ ID NO: 1 at a similar or substantially the same level as it binds to an extracellular domain of Fn14; and/or   (v) binds to an extracellular domain of Fn14 comprising an alanine substituted for the histidine at position 60 of SEQ ID NO: 1 at a similar or substantially the same level as it binds to an extracellular domain of Fn14.   
     
     
         18 . The method  claim 12 , wherein the Fn14-binding protein is an antibody comprising one or more of the following:
 (i) a V H  comprising a sequence set forth in SEQ ID NO: 15 or a humanized, synhumanized or deimmunized version thereof and a V L  comprising a sequence set forth in SEQ ID NO: 22 or a humanized, synhumanized or deimmunized version thereof or (ii) a V H  comprising a sequence set forth in SEQ ID NO: 16 or a humanized, synhumanized or deimmunized version thereof and a V L  comprising a sequence set forth in SEQ ID NO: 23 or a humanized, synhumanized or deimmunized version thereof.