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

1. A method of treating a TNFα-associated medical condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of plant cells that express a chimeric polypeptide specifically binding TNFα 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 the carboxy terminus of said first domain is translationally fused to the N-terminus of said second domain, thereby treating the TNFα-associated medical condition in the subject, wherein said TNFα-associated medical condition is an inflammatory bowel disease.

2. The method of claim 1 , wherein said chimeric polypeptide further comprises:

(iii) a third domain comprising an endoplasmic reticulum signal peptide translationally fused N-terminally to said first domain.

3. The method of claim 2 , wherein said signal peptide is a plant signal peptide.

4. The method of claim 3 , wherein said plant signal peptide is as set forth in the amino acid sequence of SEQ ID NO: 4.

5. The method of claim 2 , wherein said chimeric polypeptide is as set forth in the amino acid sequence of SEQ ID NO: 6.

6. The method of claim 2 wherein said chimeric polypeptide is as set forth in the amino acid sequence of any one of SEQ ID NO: 7, 204 or 205.

7. The method of claim 1 , wherein said chimeric polypeptide further comprises an additional domain comprising an endoplasmic reticulum retention signal translationally fused C-terminally to said second domain.

8. The method of claim 7 , wherein said endoplasmic reticulum retention signal is as set forth in the amino acid sequence of SEQ ID NO: 16.

9. The method of claim 1 , wherein said first domain is 200-250 amino acids long.

10. The method of claim 9 , wherein said first domain comprises the amino acid sequence LCAP (SEQ ID NO: 11) and VFCT (SEQ ID NO: 12).

11. The method of claim 10 , wherein said first domain further comprises the amino acid sequence LPAQVAFXPYAPEPGSTC (SEQ ID NO: 13).

12. The method of claim 11 , wherein said first domain is as set forth in the amino acid sequence of SEQ ID NO: 2.

13. The method of claim 1 , wherein said second domain is as set forth in the amino acid sequence of SEQ ID NO: 9.

14. The method of claim 1 , wherein said chimeric polypeptide is as set forth in the amino acid sequence of SEQ ID NO: 7.

15. The method of claim 1 , wherein said chimeric polypeptide is capable of inhibiting TNFα-induced apoptosis.

16. The method of claim 1 , wherein said chimeric polypeptide comprises a plant-specific glycan.

17. The method of claim 1 , wherein said chimeric polypeptide has a plant glycosylation pattern.

18. The method of claim 1 , wherein said chimeric polypeptide lacks sialic acid residues.

19. The method of claim 1 , wherein said plant cells comprise an isolated polynucleotide comprising a nucleic acid sequence encoding said chimeric polypeptide which specifically binds TNFα.

20. The method of claim 19 , wherein said nucleic acid sequence is comprised within a nucleic acid expression construct and further comprises

a cis-acting regulatory element active in a plant cell.

21. The method of claim 1 , wherein said plant cells are Nicotiana tabacum plant cells.

22. The method of claim 21 , wherein said Nicotiana tabacum plant cells are Bright Yellow (BY-2) cells.

23. The method of claim 1 , wherein said plant cells are lyophilized plant cells.

24. The method of claim 1 , wherein said plant cells are formulated for oral administration.

25. The method of claim 1 , wherein said inflammatory bowel disease is Crohn's disease.

26. The method of claim 1 , wherein said inflammatory bowel disease is ulcerative colitis.