Use of il-22 dimer in manufacture of a medicament for intravenous administration

Abstract

The present application provides methods of administering an IL-22 dimer to an individual, such as a human individual, comprising intravenously administering to the individual an effective amount of an IL-22 dimer, wherein the amount of the IL-22 dimer is about 2 µg/kg about 200 µg/kg (such as about 10 µg/kg to about 45 µg/kg), as well as methods of treating diseases by following such administration methods. Also provided are kits, unit dosages, and articles of manufacture for use in any one of the methods described herein.

1 . A method of treating a metabolic disease in a human individual, comprising intravenously administering to the human individual an effective amount of an IL-22 dimer, wherein the amount of the IL-22 dimer is about 2 µg/kg to about 200 µg/kg, wherein the IL-22 dimer comprises two monomeric subunits, wherein each monomeric subunit comprises an IL-22 domain and a dimerization domain, and wherein the dimerization domain comprises the CH2 and CH3 domains of human IgG. 
     
     
         2 . The method of  claim 1 , wherein the IL-22 dimer is administered at the amount of about 5 µg/kg to about 80 µg/kg. 
     
     
         3 . The method of  claim 1 , wherein the IL-22 dimer is administered at the amount of about 10 µg/kg to about 45 µg/kg. 
     
     
         4 . The method of  claim 1 , wherein the IL-22 dimer is administered at the amount of about 2 µg/kg to about 45 µg/kg. 
     
     
         5 . The method of  claim 1 , wherein the IL-22 dimer is administered no more than once a week. 
     
     
         6 . The method of  claim 1 , wherein the IL-22 dimer is administered no more than once a month. 
     
     
         7 . The method of  claim 1 , wherein the IL-22 dimer is administered no more than once every three months. 
     
     
         8 . The method of  claim 1 , wherein each monomeric subunit comprises the IL-22 domain linked to the dimerization domain via a linker sequence. 
     
     
         9 . The method of  claim 8 , wherein the linker sequence is about 6 to about 30 amino acids in length. 
     
     
         10 . The method of  claim 9 , wherein the linker sequence comprises the amino acid sequence of SEQ ID NO: 1 or 10. 
     
     
         11 . The method of  claim 1 , wherein the dimerization domain of each monomeric subunit comprises at least two cysteines capable of forming intermolecular disulfide bonds. 
     
     
         12 . The method of  claim 1 , wherein the IgG is IgG2 or IgG4. 
     
     
         13 . The method of  claim 1 , wherein the dimerization domain of each monomeric subunit comprises the amino acid sequence of SEQ ID NO: 2 or 9. 
     
     
         14 . The method of  claim 1 , wherein the IL-22 domain of each monomeric subunit comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         15 . The method of  claim 1 , wherein the IL-22 domain is fused to the N-terminus of the dimerization domain within each monomeric subunit. 
     
     
         16 . The method of  claim 1 , wherein the IL-22 domain is fused to the C-terminus of the dimerization domain within each monomeric subunit. 
     
     
         17 . The method of  claim 1 , wherein each monomeric subunit comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 4 and 6-8. 
     
     
         18 . The method of  claim 1 , wherein the metabolic disease is selected from the group consisting of: diabetes, hyperlipidemia, hyperglycemia, and obesity. 
     
     
         19 . The method of  claim 1 , wherein the method achieves one or more effects selected from the group consisting of: losing weight, reducing adipocyte size, reducing deposition of triglycerides, and improving glucose tolerance. 
     
     
         20 . A kit for intravenous administration of an IL-22 dimer for treating a metabolic disease in a human individual, comprising: 1) a composition comprising the IL-22 dimer and a pharmaceutically acceptable excipient suitable for intravenous administration; and 2) an instruction for intravenously administering the IL-22 dimer to the human individual at a dose of about 2 µg/kg to about 200 µg/kg for treating the metabolic disease; wherein the IL-22 dimer comprises two monomeric subunits, wherein each monomeric subunit comprises an IL-22 domain and a dimerization domain, and wherein the dimerization domain comprises the CH2 and CH3 domains of human IgG.