Immunoglobulin chimeric monomer-dimer hybrids

Abstract

The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

1 - 194 . (canceled) 
     
     
         195 . A chimeric protein comprising a first chain and a second chain,
 wherein said first chain comprises a cytokine, a polyethylene glycol (PEG) linker, and a first Fc fragment of an Immunoglobulin G (IgG),   wherein the cytokine is linked to the N-terminus of the first Fc fragment by the PEG linker,   wherein said second chain comprises a second Fc fragment of an IgG without a biologically active molecule or immunoglobulin variable region, and   wherein said first Fc fragment and said second Fc fragment are associated by at least one disulfide bond.   
     
     
         196 . The chimeric protein of  claim 195 , wherein the IgG4 is human IgG4. 
     
     
         197 . The chimeric protein of  claim 196 , wherein the human IgG4 is aglycosylated. 
     
     
         199 . The chimeric protein of  claim 195 , wherein the chimeric protein is produced by a production process comprising the following steps:
 expressing the first and second Fc fragments of Immunoglobulin G (IgG) in  E. coli , such that the first and second Fc fragments are associated by the at least one disulfide bond,   isolating the first and second Fc fragments, and   linking the first Fc fragment with the cytokine by the PEG linker.   
     
     
         200 . A pharmaceutical composition comprising the chimeric protein of  claim 195  and a pharmaceutically acceptable excipient. 
     
     
         201 . A chimeric protein of the formula
   X-L a -F:F or F:F-L a -X   wherein
 X is a cytokine, 
 L is a polyethylene glycol (PEG) linker, 
 F is an Fc fragment of an Immunoglobulin G (IgG), 
 a is 1, and 
 : is a chemical association comprising at least one covalent bond. 
   
     
     
         202 . The chimeric protein of  claim 201 , wherein the at least one covalent bond comprises a disulfide bond. 
     
     
         203 . The chimeric protein of  claim 201 , wherein the IgG is IgG4. 
     
     
         204 . The chimeric protein of  claim 203 , wherein the IgG4 is human IgG4. 
     
     
         205 . The chimeric protein of  claim 204 , wherein the human IgG4 is aglycosylated. 
     
     
         206 . A pharmaceutical composition comprising the chimeric protein of  claim 201  and a pharmaceutically acceptable excipient.