Reversible linkers and use thereof

Abstract

Disclosed herein are compositions and methods for preparation and delivery of protein therapeutics, and more particularly reversible linkers and use thereof.

1 - 18 . (canceled) 
     
     
         19 . A composition comprising a plurality of protein monomers, wherein each protein monomer is reversibly linked to another protein monomer through a degradable linker so as to form the following structure, in which each protein monomer is represented by an “R”: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The composition of  claim 19 , prepared by cross-linking the plurality of protein monomers, each having amine groups, with the degradable linker having formula (B): 
       
         
           
           
               
               
           
         
       
     
     
         21 . The composition of  claim 19 , wherein the protein monomer comprises one or more cytokine molecules. 
     
     
         22 . The composition of  claim 21 , wherein the one or more cytokine molecules are selected from the group consisting of IL-15, IL-2, IL-7, IL-10, IL-12, IL-18, IL-21, IL-23, IL-4, IL-1α, IL-1β, IL-5, IFNγ, TNFα, IFNα, IFNβ, GM-CSF, and GCSF. 
     
     
         23 . The composition of  claim 22 , wherein the protein monomer comprises a cytokine molecule coupled to an immunoglobulin Fc region or an antibody molecule. 
     
     
         24 . The composition of  claim 22 , wherein the protein monomer comprises an IL-15 molecule and an extracellular domain of an IL-15 receptor alpha. 
     
     
         25 . The composition of  claim 24 , wherein the protein monomer comprises an IL-15 molecule and an extracellular domain of an IL-15 receptor alpha coupled to an immunoglobulin Fc region or antibody molecule. 
     
     
         26 . The composition of  claim 22 , wherein the protein monomer comprises an IL-15 molecule and a soluble IL-15 receptor alpha domain fused to an immunoglobulin Fc region.