Methods of using interleukin-10 for treating diseases and disorders

Abstract

Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.

1 .- 68 . (canceled) 
     
     
         69 . A method of treating hyperlipidemia in a subject suffering therefrom, wherein the subject has a deficiency in function in LDL receptor function, the method comprising administering to the subject a therapeutically effective amount of a PEG-IL-10 agent, wherein the amount administered is sufficient to maintain an IL-10 serum trough concentration in the range from 1.0 pg/mL to 10.0 ng/mL over a period of time of at least 24 hours. 
     
     
         70 . The method of  claim 69 , wherein the IL-10 serum trough concentration is maintained in the range from 1.0 pg/mL to 1.0 ng/mL. 
     
     
         71 . The method of  claim 69 , wherein the PEG-IL-10 agent comprises mature human IL-10. 
     
     
         72 . The method of  claim 69 , wherein the PEG-IL-10 agent comprises a variant of human IL-10, and wherein the variant exhibits activity comparable to the activity of human IL-10. 
     
     
         73 . The method of  claim 71 , wherein the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one subunit of mature human IL-10. 
     
     
         74 . The method of  claim 73 , wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10. 
     
     
         75 . The method of  claim 74 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa. 
     
     
         76 . The method of  claim 74 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass greater than about 20 kDa. 
     
     
         77 . The method of  claim 76  wherein the PEG component is a branched PEG. 
     
     
         78 . The method of  claim 74 , wherein at least one PEG molecule is covalently attached to the at least one IL-10 subunit via a linker. 
     
     
         78 . The method of  claim 69 , wherein the PEG-IL-10 agent is administered to the subject at least once daily. 
     
     
         79 . The method of  claim 78 , wherein the administering is by parenteral injection. 
     
     
         80 . The method of  claim 79 , wherein the parenteral injection is subcutaneous. 
     
     
         81 . The method of  claim 69 , wherein the hyperlipidemia is familial hypercholesterolemia. 
     
     
         82 . The method of  claim 69 , wherein the method comprises administering at least one additional prophylactic or therapeutic agent. 
     
     
         83 . The method of  claim 82  wherein the additional prophylactic or therapeutic agent is selected from the group consisting of cholesterol absorption inhibitors, HMG-CoA reductase inhibitors, fibrates, bile acid sequestrants, niacins and PCSK9 inhibitors. 
     
     
         84 . The method of  claim 83  wherein the additional prophylactic or therapeutic agent is a PCSK9 inhibitor. 
     
     
         85 . The method of  claim 84  wherein the PCSK9 inhibitor is selected from the group consisting of AMG145, 1D05-IgG2 and SAR236553/REGN727. 
     
     
         86 . The method of  claim 83  wherein the additional prophylactic or therapeutic agent is a cholesterol absorption inhibitor. 
     
     
         87 . The method of  claim 83  wherein the additional prophylactic or therapeutic agent is HMG-CoA reductase inhibitor.