Immunoglobulin constant region fc receptor binding agents

Abstract

IVIG replacement compounds are derived from recombinant and/or biochemical creation of immunologically active biomimetic(s). These replacement compounds are then screened in vitro to assess each replacement compound's efficiency at modulating immune function. Particular replacement compounds are selected for further in vivo validation and dosage/administration optimization. Finally, the replacement compounds are used to treat a wide range of diseases, including inflammatory and autoimmune diseases.

1 .- 170 . (canceled) 
     
     
         171 . A polypeptide comprising:
 at least a first and second Fc fragment of IgG;   at least one of the first and second Fc fragments of IgG comprising at least one CH2 domain and at least one hinge region;   the first and second Fc fragments of IgG being bound through the at least one hinge region;   wherein the polypeptide terminates with a second hinge region.   
     
     
         172 . The polypeptide of  claim 171 , wherein the at least one of the first and second Fc fragments of IgG further comprises at least one CH3 domain. 
     
     
         173 . The polypeptide of  claim 171 , wherein the at least one of the first and second Fc fragments of IgG comprises one CH2 domain, one CH3 domain, and one hinge region. 
     
     
         174 . The polypeptide of  claim 171 , wherein the at least one first and second Fc fragments of IgG form a chain and the polypeptide further comprises multiple substantially similar chains bound to at least one other of said multiple chains in a substantially parallel relationship. 
     
     
         175 . The polypeptide of  claim 174 , wherein two parallel chains form a dimer. 
     
     
         176 . The polypeptide of  claim 174 , wherein multiple parallel chains form a multimer. 
     
     
         177 . The polypeptide of  claim 171 , wherein the Fc fragments of IgG are from an Fc fragment of mammalian IgG. 
     
     
         178 . The polypeptide of  claim 171 , wherein the Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, an Fc fragment of human IgG, and any combinations thereof. 
     
     
         179 . The polypeptide of  claim 178 , wherein the Fc fragment of IgG is a murine Fc fragment of IgG. 
     
     
         180 . The polypeptide of  claim 178 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4, and any combinations thereof. 
     
     
         181 . The polypeptide of  claim 171 , wherein the polypeptide is synthetic or recombinant. 
     
     
         182 . The polypeptide of  claim 175 , wherein the polypeptide is configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell. 
     
     
         183 . The polypeptide of  claim 182 , wherein upon binding and crosslinking the at least two Fc-gamma receptors on a stimulated cell, the polypeptide induces the stimulated cell to produce an anti-inflammatory cytokine Interleukin-10. 
     
     
         184 . The polypeptide of  claim 182 , wherein the stimulated cell is a leukocyte. 
     
     
         185 . The polypeptide of  claim 184 , wherein the leukocyte is selected from a group consisting of macrophages, dendritic cells, and B-cells. 
     
     
         186 . A polypeptide comprising:
 at least a first and second Fc fragment of IgG;   at least one of the first and second Fc fragments of IgG comprising one CH2 domain, one CH3 domain, and one hinge region;   the first and second Fc fragments of IgG being bound through the at least one hinge region;   wherein the polypeptide is encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 21, 23, and 25.   
     
     
         187 . A polypeptide comprising:
 at least a first and second Fc fragment of IgG;   at least one of the first and second Fc fragments of IgG comprising one CH2 domain, one CH3 domain, and one hinge region;   the first and second Fc fragments of IgG being bound through the at least one hinge region;   wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 22, 23, 24, 25, 26, 38, 39, 43, 44, 46, 47, 53, 57, and 58.   
     
     
         188 . The polypeptide of  claim 171 , wherein the at least one first and second Fc fragments of IgG form a first chain and the polypeptide further comprises a second chain bound in a substantially parallel relationship to the first chain to form a dimer;
 wherein the dimer is configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell to thereby induce the stimulated cell to produce an anti-inflammatory cytokine Interleukin-10 upon binding and cross-linking the at least two Fc-gamma receptors.   
     
     
         189 . A polypeptide comprising:
 at least a first and second Fc fragment of IgG;   at least one of the first and second FC fragments of IgG comprising at least one CH2 domain and at least one hinge region;   the first and second Fc fragments of IgG being bound through the at least one hinge region;   wherein the polypeptide does not comprise a variable region.   
     
     
         190 . The polypeptide of  claim 189 , wherein the at least one first and second Fc fragments of IgG form a chain and the polypeptide further comprises multiple substantially similar chains bound to at least one other of said multiple chains in a substantially parallel relationship. 
     
     
         191 . The polypeptide of  claim 190 , wherein two parallel chains form a dimer. 
     
     
         192 . The polypeptide of  claim 190 , wherein multiple parallel chains form a multimer. 
     
     
         193 . The polypeptide of  claim 171 , further comprising at least one region comprising a protein expression system. 
     
     
         194 . The polypeptide of  claim 174 , further comprising at least one region comprising a protein expression system. 
     
     
         195 . The polypeptide of  claim 175 , further comprising at least one region comprising a protein expression system. 
     
     
         196 . The polypeptide of  claim 176 , further comprising at least one region comprising a protein expression system. 
     
     
         197 . The polypeptide of  claim 187 , wherein the polypeptide terminates with a second hinge region. 
     
     
         198 . The polypeptide of  claim 197 , wherein the at least one first and second Fc fragments of IgG form a chain and the polypeptide further comprises multiple substantially similar chains bound to at least one other of said multiple chains in a substantially parallel relationship. 
     
     
         199 . The polypeptide of  claim 198 , wherein two parallel chains form a dimer. 
     
     
         200 . The polypeptide of  claim 198 , wherein multiple parallel chains form a multimer.