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 replacements 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 method for treatment of a mammalian subject for an autoimmune or inflammatory disease, the method comprising:
 administering to the mammalian subject an effective amount of a polymeric protein comprising five, six or seven polypeptide monomer units;   wherein each polypeptide monomer unit comprises an Fc receptor binding portion comprising two immunoglobulin G heavy chain constant regions;   wherein each immunoglobulin G heavy chain constant region comprises a cysteine residue which is linked via a disulfide bond to a cysteine residue of an immunoglobulin G heavy chain constant region of an adjacent polypeptide monomer unit;   wherein the polymeric protein does not comprise a further immunomodulatory portion;   or an antigen portion that causes antigen-specific immunosuppression when administered to the mammalian subject.   
     
     
         172 . The method of  claim 171  wherein each polypeptide monomer unit comprises a tailpiece region fused to each of the two immunoglobulin G heavy chain constant regions;
 wherein the tailpiece region of each polypeptide monomer unit facilitates the assembly of the monomer units into a polymer. 
 
     
     
         173 . The method of  claim 172  wherein the tailpiece region is an IgM or IgA tailpiece, or fragment or variant thereof. 
     
     
         174 . The method of  claim 171  wherein each of the immunoglobulin G heavy chain constant regions comprises an amino acid sequence having at least 90% sequence identity to a native human immunoglobulin G1 heavy chain constant region. 
     
     
         175 . The method of  claim 171  wherein each of the immunoglobulin G heavy chain constant regions comprises an amino acid sequence which is modified compared to the amino acid sequence of a native immunoglobulin G heavy chain constant region, to modify the affinity of the Fc receptor binding portion for at least one Fc receptor. 
     
     
         176 . The method of  claim 171  wherein each of the immunoglobulin G heavy chain constant regions comprises an amino acid sequence which is modified compared to the amino acid sequence of a native immunoglobulin G heavy chain constant region, to increase the in vivo half life of the polymeric protein, suitably by increasing the affinity of the Fc receptor binding portion for neonatal Fc receptor. 
     
     
         177 . The method of  claim 171  wherein the autoimmune or inflammatory disease is treatable with Intravenous immunoglobulin (IVIG). 
     
     
         178 . The method of  claim 171  wherein the autoimmune or inflammatory disease is an autoimmune cytopenia, idiopathic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, asthma, Kawasaki disease, Guillain-Barre syndrome, Stevens-Johnson syndrome, Crohn's colitis, diabetes, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, anti-Factor VIII autoimmune disease, dermatomyositis, vasculitis, and uveitis or Alzheimer's disease. 
     
     
         179 . A method for treatment of a mammalian subject for an autoimmune or inflammatory disease, the method comprising:
 administering to the mammalian subject an effective amount of a polymeric protein consisting of five, six or seven polypeptide monomer units;   wherein each polypeptide monomer unit consists of an Fc receptor binding portion consisting of two immunoglobulin G heavy chain constant regions; and, optionally, a polypeptide linker linking the two immunoglobulin G heavy chain constant regions as a single chain Fc; and   wherein each immunoglobulin G heavy chain constant region comprises a cysteine residue which is linked via a disulfide bond to a cysteine residue of an immunoglobulin G heavy chain constant region of an adjacent polypeptide monomer unit.   
     
     
         180 . A method for treatment of a mammalian subject for an autoimmune or inflammatory disease, the method comprising:
 administering to the mammalian subject an effective amount of a polymeric protein consisting of five, six or seven polypeptide monomer units;   wherein each polypeptide monomer unit consists of an Fc receptor binding portion and a tailpiece region;   wherein the Fc receptor binding portion consists of two immunoglobulin G heavy chain constant regions; and, optionally, a polypeptide linker linking the two immunoglobulin G heavy chain constant regions as a single chain Fc;   wherein each modified human immunoglobulin G heavy chain constant region comprises a cysteine residue which is linked via a disulfide bond to a cysteine residue of a modified human immunoglobulin G heavy chain constant region of an adjacent polypeptide monomer unit; and   wherein the tailpiece region is fused to each of the two modified human immunoglobulin G heavy chain constant regions of the polypeptide monomer unit, and facilitates the assembly of the monomer units into a polymer.   
     
     
         181 . The method of  claim 180  wherein the tailpiece region is an IgM or IgA tailpiece, or fragment or variant thereof.