Method of treating a metabolic disorder of the liver

Abstract

A method of treating a metabolic disorder of the liver includes administering a therapeutic agent. The therapeutic agent includes an IL-22 polypeptide and an antigen-binding molecule. The IL-22 polypeptide is fused or otherwise conjugated, directly or indirectly, to the antigen-binding molecule, and the antigen-binding molecule is an antibody or antigen-binding fragment that includes heavy and light chain CDR sequences.

What is claimed is: 
     
         1 . A method of treating a metabolic disorder of the liver, comprising administering a therapeutic agent comprising an IL-22 polypeptide and an antigen-binding molecule, wherein the IL-22 polypeptide is fused or otherwise conjugated, directly or indirectly, to the antigen-binding molecule, and the antigen-binding molecule is an antibody or antigen-binding fragment that comprises heavy chain CDR sequences comprising a CDR1 of SEQ ID NO: 62, a CDR2 selected from the group consisting of SEQ ID NOs: 63 to 67, and a CDR3 selected from the group consisting of SEQ ID NOs: 68 to 71; and light chain CDR sequences comprising a CDR1 of SEQ ID NO: 72, a CDR2 selected from the group consisting of SEQ ID NOs: 73 to 77, and a CDR3 selected from the group consisting of SEQ ID NOs: 78 to 82. 
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen-binding fragment comprises heavy chain CDR sequences comprising a CDR1 of SEQ ID NO: 62, a CDR2 of SEQ ID NO: 63, and a CDR3 of SEQ ID NO: 68; and light chain CDR sequences comprising a CDR1 of SEQ ID NO: 72, a CDR2 of SEQ ID NO: 73, and a CDR3 of SEQ ID NO: 78. 
     
     
         3 . The method of  claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 47 to 51; and a light chain variable sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 52 to 56. 
     
     
         4 . The method of  claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 47 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO: 52. 
     
     
         5 . The method of  claim 1 , wherein the antigen-binding molecule is a single chain antibody. 
     
     
         6 . The method of  claim 1 , wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         7 . The method of  claim 1 , wherein the antigen-binding molecule is fused or otherwise conjugated, directly or indirectly, to the C-terminus of the IL-22 polypeptide. 
     
     
         8 . The method of  claim 1 , wherein the antigen-binding molecule is fused or otherwise conjugated, directly or indirectly, to the N-terminus of the IL-22 polypeptide. 
     
     
         9 . The method of  claim 1 , wherein the antigen-binding molecule is conjugated to the IL-22 polypeptide via an intervening linker. 
     
     
         10 . The method of  claim 9 , wherein the linker is a peptide. 
     
     
         11 . The method of  claim 10 , wherein the peptide linker comprises the amino acid sequence GGGGS. 
     
     
         12 . The method of  claim 1 , wherein the antigen-binding molecule is conjugated to the C-terminus of the IL-22 polypeptide via a peptide linker. 
     
     
         13 . The method of  claim 1 , wherein the antigen-binding molecule is conjugated to the N-terminus of the IL-22 polypeptide via a peptide linker. 
     
     
         14 . The method according to  claim 1 , wherein the antigen-binding molecule is a single chain antibody comprising heavy chain CDR sequences comprising a CDR1 of SEQ ID NO: 62, a CDR2 of SEQ ID NO: 63, and a CDR3 of SEQ ID NO: 68; and light chain CDR sequences comprising a CDR1 of SEQ ID NO: 72, a CDR2 of SEQ ID NO: 73, and a CDR3 of SEQ ID NO: 78, and wherein the antigen-binding molecule is conjugated to the C-terminus of the IL-22 polypeptide via a peptide linker. 
     
     
         15 . The method according to  claim 1 , wherein the therapeutic agent comprises the amino acid sequence of SEQ ID NO: 285. 
     
     
         16 . The method of  claim 1 , wherein the metabolic disorder of the liver is non-alcoholic steatohepatitis (NASH). 
     
     
         17 . The method of  claim 1 , wherein the metabolic disorder of the liver is non-alcoholic fatty liver disease (NAFLD).