Actriib binding agents and uses thereof

Abstract

The disclosure provides, among other aspects, neutralizing antibodies and portions thereof that bind to ActRIIB and uses for same.

We claim: 
     
         1 . An anti-ActRIIB antibody or functional fragment thereof that binds to ActRIIB between amino acids 19-134 of SEQ ID NO:1. 
     
     
         2 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof binds to ActRIIB with a K D  of 1 nM or less. 
     
     
         3 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof inhibits myostatin binding to ActRIIB. 
     
     
         4 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof inhibits myostatin induced signaling as measured by a Smad dependent reporter gene assay. 
     
     
         5 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof binds to ActRIIB with a 10-fold or greater affinity that it binds to ActRIIA. 
     
     
         6 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof binds to an epitope selected from the group consisting of: amino acids 77-83 of SEQ ID NO:1, amino acids 60-64 of SEQ ID NO:1, 73-74 of SEQ ID NO:1, amino acids 73-83 of SEQ ID NO:1, amino acids 98-101 of SEQ ID NO:1; amino acids 35-39 of SEQ II) NO:1 and amino acids 52-55 of SEQ ID NO:1. 
     
     
         7 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof is of the IgG1 isotype. 
     
     
         8 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof is characterized by an altered effector function through mutation of the Fc region. 
     
     
         9 . An isolated polynucleotide sequence encoding the antibody or functional fragment thereof according to  claim 1 . 
     
     
         10 . A cloning or expression vector comprising the isolated polynucleotide sequence according to  claim 9 . 
     
     
         11 . An isolated host cell comprising the vector according to  claim 10 . 
     
     
         12 . A process for the production of an antibody or functional fragment thereof that binds to ActRIIB between amino acids 19-1344 of SEQ ID NO:1, comprising culturing the host cell of  claim 11  and isolating the antibody or functional fragment thereof. 
     
     
         13 . A pharmaceutical composition comprising the anti-ActRIIB antibody or functional fragment thereof according to  claim 1 . 
     
     
         14 . The pharmaceutical composition of  claim 13 , where the composition further comprises a pharmaceutically acceptable diluent or carrier. 
     
     
         15 . The antibody or fragment thereof of  claim 2  that comprises at least one, at least two, at least three, at least four, at least five or at least six CDR sequences having at least 80% identity to a CDR selected from the group consisting of SEQ ID NOs: 37-42. 
     
     
         16 . The antibody or fragment thereof according to  claim 15  wherein said percent identity is at least 85%. 
     
     
         17 . The antibody or fragment thereof according to  claim 15  wherein said percent identity is at least 90%. 
     
     
         18 . The antibody or fragment thereof according to  claim 15  wherein said percent identity is 95%. 
     
     
         19 . The antibody or fragment thereof according to  claim 15  wherein said percent identity is 100%.