Chimeric polypeptides, polynucleotides encoding same, cells expressing same and methods of producing same

Abstract

A plant produced chimeric polypeptide is provided. The plant produced chimeric polypeptide comprising: (i) a first domain which comprises a TNF Alpha binding domain of a TNF receptor, and (ii) a second domain which comprises an Fc domain of an immunoglobulin, wherein the first domain and the second domain are N-terminally to C-terminally respectively sequentially translationally fused and wherein the chimeric polypeptide specifically binds TNF Alpha.

What is claimed is: 
     
         1 . An oral dosage form comprising the plant cells comprising a nucleic acid construct having a nucleic acid sequence encoding a plant produced chimeric polypeptide comprising:
 (i) a first domain which comprises a TNFα binding domain of a TNF receptor, and   (ii) a second domain which comprises an Fc domain of an immunoglobulin, wherein said first domain and said second domain are N-terminally to C-terminally respectively sequentially translationally fused and wherein the chimeric polypeptide specifically binds TNFα, the oral dosage form comprising 1-20 mg of said polypeptide.   
     
     
         2 . The oral dosage form of  claim 1  comprising 1-10 mg of said polypeptide. 
     
     
         3 . The oral dosage form of  claim 1  comprising 10-20 mg of said polypeptide. 
     
     
         4 . The oral dosage form of  claim 1 , wherein said chimeric polypeptide comprises an additional domain encoding an endoplasmic reticulum signal peptide translationally fused N-terminally to said first domain. 
     
     
         5 . The oral dosage form of  claim 4 , wherein said signal peptide is a plant signal peptide. 
     
     
         6 . The oral dosage form of  claim 5 , wherein said plant signal peptide is as set forth in SEQ ID NO: 4. 
     
     
         7 . The oral dosage form of  claim 1 , wherein said first domain is 200-250 amino acids long. 
     
     
         8 . The oral dosage form of  claim 7 , wherein said first domain comprises the amino acid sequence LCAP (SEQ ID NO: 11) and VFCT (SEQ ID NO: 12). 
     
     
         9 . The oral dosage form of  claim 8 , wherein said first domain further comprises the amino acid sequence LPAQVAFXPYAPEPGSTC (SEQ ID NO: 13). 
     
     
         10 . The oral dosage form of  claim 9 , wherein said first domain is as set forth in SEQ ID NO: 2. 
     
     
         11 . The oral dosage form of  claim 1 , wherein said immunoglobulin is IgG 1 . 
     
     
         12 . The oral dosage form of  claim 1 , wherein said second domain is as set forth in SEQ ID NO: 9. 
     
     
         13 . The oral dosage form of  claim 1 , wherein said chimeric polypeptide is as set forth in SEQ ID NO: 6. 
     
     
         14 . The oral dosage form of  claim 1 , wherein said chimeric polypeptide is as set forth in SEQ ID NO: 7. 
     
     
         15 . The oral dosage form of  claim 1 , wherein said chimeric polypeptide comprises a plant-specific glycan. 
     
     
         16 . A method of treating a TNFα-associated medical condition in a subject in need thereof, the method comprising orally administering to the subject a therapeutically effective amount of the oral dosage form of  claim 1 . 
     
     
         17 . The method of  claim 16 , wherein said medical condition is an inflammatory disease. 
     
     
         18 . The method of  claim 16 , wherein said medical condition is an autoimmune disease. 
     
     
         19 . The method of  claim 16 , wherein said medical condition is selected from the group consisting of rheumatoid arthritis, ankylosing spondyloarthritis, plaque psoriasis, rheumatoid polyarthritis, psoriatic arthritis, ankylosing spondyloarthritis and juvenile idiopathic arthritis. 
     
     
         20 . The method of  claim 16 , wherein said medical condition is an inflammatory bowel disease.