PP14 fusion proteins and methods for making and using the same

Abstract

Novel fusion proteins comprising PP14 are disclosed. The fusion proteins retain the immunoregulatory function of native PP14, but offer significant advantages. Methods for using the fusion proteins, and sequence encoding the same in the treatment of immune system diseases and disorders are therefore also disclosed, as are methods for recombinant production of the present fusion proteins.

1 - 13 . (canceled)  
     
     
         14 . A method for treating an immune system disorder in a patient by administering to said patient an effective amount of a genetic sequence encoding a recombinant fusion protein comprising a first domain comprising a PP14 polypeptide sequence and a second domain comprising a polypeptide sequence of the Fc region of an immunoglobulin protein.  
     
     
         15 . The method of  claim 14 , wherein said immune system disorder is selected from the group consisting of autoimmune, alloimmune, allergic, inflammatory and lymphoproliferative disorders.  
     
     
         16 . The method of  claim 14 , wherein administration is by a method selected from the group consisting of intravenous injection, intramuscular injection, intraarticular administration, oral administration, topical administration, rectal administration, and inhalation.  
     
     
         17 . The method of  claim 14 , wherein said immune system disorder is selected from the group consisting of arthritis, asthma, graft-versus-host disease, organ rejection, systemic lupus erythematosus, atopic allergy, inflammatory bowel disease, multiple sclerosis, systemic sclerosis, allergic dermatitis, psoriasis, autoimmune thyroiditis, autoimmune liver disease, and sarcoidosis.  
     
     
         18 . The method of  claim 14 , wherein said immune system disorder is rheumatoid arthritis.  
     
     
         19 . The method of  claim 14 , wherein said immune system disorder is a lymphoproliferative disorder.  
     
     
         20 . The method of  claim 19 , wherein said lymphoproliferative disorder is selected from the group consisting of malignant non-Hodgkin's lymphoma, Hodgkin's disease, and malignant histiocytosis.  
     
     
         21 . The method of  claim 14 , wherein said immune system disorder is a neoplastic disorder.  
     
     
         22 . The method of  claim 21 , wherein said neoplastic disorder is leukemia.  
     
     
         23 . The method of  claim 14 , wherein said effective amount is that amount necessary to achieve a PP14 concentration in the blood of at least 0.1 μM/L.  
     
     
         24 . (canceled)  
     
     
         25 . A method for inhibiting interleukin-1 production in a patient comprising administering to said patient a genetic sequence encoding a recombinant fusion protein comprising a first domain comprising a PP14 polypeptide sequence and a second domain comprising a polypeptide sequence of the Fc region of an immunoglobulin protein, in an amount effective to inhibit interleukin-1 production.  
     
     
         26 . A method for inhibiting a TH1 cytokine response in a patient comprising administering to said patient a genetic sequence encoding a recombinant fusion protein comprising a first domain comprising a PP14 polypeptide sequence and a second domain comprising a polypeptide sequence of the Fc region of an immunoglobulin protein, in an amount effective to inhibit said response.  
     
     
         27 . The method of  claim 14 , wherein said Fc region of said fusion protein is the Fc region of immunoglobin IgG1.  
     
     
         28 . The method of  claim 14 , wherein said Fc region of said fusion protein is selected from the group consisting of IgG2a, IgG2b, IgG3, IgG4, IgM, IgA and IgE.  
     
     
         29 . The method of  claim 27 , wherein said Fc region is the multi-domain Fc region from a human immunoglobulin protein.  
     
     
         30 . The method of  claim 14 , said fusion protein further comprising one or more of an epitope tag or a leucine zipper.  
     
     
         31 . The method of  claim 30 , wherein said epitope tag is a polyhistidine tag.