Method of use of transgenic plant expressed antibodies
The present invention relates to expression and assembly of foreign multimeric proteins—e.g., antibodies—in plants, as well as to transgenic plants that express such proteins. In one of several preferred embodiments, the generation and assembly of functional secretory antibodies in plants is disclosed. The invention also discloses compositions produced by the transgenic plants of the present invention and methods of using same.
1. A method of passively immunizing a human or non-human animal subject against a preselected antigen using an immunoglobulin molecule produced in transgenic plants, said method comprising
(a) obtaining a source of antigen-specific immunoglobulin from transgenic plant cells producing antigen specific immunoglobulin, said plant cells containing nucleotide sequences encoding an immunoglobulin heavy chain polypeptide and an immunoglobulin light chain polypeptide wherein said nucleotide sequences also encode a leader sequence for each polypeptide wherein each leader sequence forms a secretion signal that is cleaved from each of said immunoglobulin heavy chain and light chain polypeptides following proteolytic processing; and
(b) administering therapeutic amount of said antigen-specific immunoglobulin molecule to said subject, thereby passively immunizing a human or non-human animal subject against a preselected antigen.
2. The method of claim 1 , wherein said immunoglobulin molecule is administered as part of a composition, which composition further comprises a material having nutritional value.
3. The method of claim 2 , wherein said material having nutritional value is from a plant or an animal.
4. The method of claim 1 , wherein said immunoglobulin molecule is administered as part of a composition, which composition further comprises a physiologically inert material.
5. The method of claim 1 , wherein said immunoglobulin heavy chain is a fragment of a full-length heavy chain.
6. The method of claim 1 , wherein said immunoglobulin light chain is a fragment of a full length light chain.
7. The method of claim 1 , wherein said preselected antigen is from a pathogen.
8. The method of claim 7 , wherein said pathogen is selected from bacterial, viruses, or parasites.
9. The method of claim 7 , wherein the pathogen is E. Coli, Salmonellae, Vibrio cholerae , or Salmonellae typhimurium.
10. The method of claim 1 , wherein the plant cells are from a monocot.
11. The method of claim 1 , wherein the plant cells are from a dicot.
12. The method of claim 1 , wherein the leader sequence is a non-native leader sequence.
13. The method of claim 1 , wherein the leader sequence is a yeast leader sequence.
14. The method of claim 1 , wherein the leader sequence is a plant leader sequence.
15. The method of claim 1 , wherein the immunoglobulin heavy chain comprises at least a portion of a constant region and said constant region is from an IgA heavy chain.
16. The method of claim 1 , wherein the immunoglobulin heavy chain comprises at least a portion of a constant region and said constant region is from an IgG heavy chain.
17. The method of claim 1 , wherein said heavy chain is full length.
18. The method of claim 1 , wherein said light chain is full length.
19. The method of claim 1 , wherein said immunoglobulin molecule is glycosylated and free from detectable sialic acid residues.
20. The method of claim 1 , wherein said immunoglobulin molecule is a fragment of a full-length immunoglobulin.
21. The method of claim 20 , wherein said fragment is a Fab.
22. The method of claim 20 , wherein said fragment is a Fab′.
23. The method of claim 20 , wherein said fragment is a F(ab′)2.
24. The method of claim 20 , wherein said fragment is an Fv.
25. The method of claim 1 , wherein the plant cells are alga cells.
26. The method of claim 1 wherein said plant cells are in the form of a plant.
27. A method of passively immunizing a human or non-human animal subject against a preselected antigen by administering an immunoglobulin produced by transgenic plant cells, said method comprising obtaining a formulation comprising an antigen-specific immunoglobulin by processing plant cells containing nucleotide sequences encoding an immunoglobulin heavy chain and an immunoglobulin light chain wherein said nucleotide sequences also encode a leader sequence for said heavy chain and said light chain and wherein each leader sequence forms a secretion signal that is cleaved from each of said immunoglobulin heavy chain and light chain polypeptides following proteolytic processing and administering to said subject a therapeutic amount of said formulation comprising said antigen-specific immunoglobulin produced from transgenic plants.
28. The method of claim 27 , wherein said immunoglobulin heavy chain is a fragment of a full-length heavy chain.
29. The method of claim 27 , wherein said heavy chain is full length.
30. The method of claim 27 , wherein said immunoglobulin light chain is a fragment of a full length light chain.
31. The method of claim 27 , wherein said light chain is full length.
32. The method of claim 27 , wherein said heavy chain and said light chain are full length.
33. The method of claim 27 , wherein said heavy chain is a fragment of a full length heavy chain and said light chain is a fragment of a full length light chain.
34. The method of claim 27 , wherein said heavy chain includes at least a portion of a constant region and wherein said constant region is from an IgA antibody.
35. The method of claim 27 , wherein said heavy chain includes at least a portion of a constant region and wherein said constant region is from an IgG antibody.
36. The method of claim 27 , wherein said heavy chain includes at least a portion of a constant region and wherein said constant region is from an IgM antibody.
37. The method of claim 27 , wherein said immunoglobulin molecule is glycosylated and free from detectable sialic acid residues.
38. The method of claim 27 , wherein said immunoglobulin is a fragment of a full-length immunoglobulin.
39. The method of claim 38 , wherein said fragment is a Fab.
40. The method of claim 38 , wherein said fragment is a Fab′.
41. The method of claim 38 , wherein said fragment is a F(ab′)2.
42. The method of claim 38 , wherein said fragment is an Fv.
43. The method of claim 27 , wherein said preselected antigen is from a pathogen.
44. The method of claim 43 , wherein said pathogen is selected from bacteria, viruses, or parasites.
45. The method of claim 43 , wherein said pathogen is E. Coli, Salmonellae, Vibrio cholerae , or Salmonellae typhimurium.
46. The method of claim 27 , wherein the plant cells are from a monocot.
47. The method of claim 27 , wherein the plant cells are from a dicot.
48. The method of claim 27 , wherein the plant cells are from an alga.
49. The method of claim 27 , wherein the leader sequence is a non-native leader sequence.
50. The method of claim 27 , wherein said immunoglobulin is formulated with a pharmaceutically acceptable carrier.
51. The method of claim 27 , wherein said plant cells are in the form of a plant.
52. A method of passively immunizing a human or non-human animal subject against a preselected antigen by administering an immunoglobulin produced by transgenic plant cells, said method comprising:
(a) preparing plant cells containing
nucleotide sequences encoding a dual chain immunoglobulin product comprising an immunoglobulin heavy chain and an immunoglobulin light chain wherein said nucleotide sequences also encode a leader sequence for each of said heavy chain and light chain, and antigen-specific immunoglobulin encoded by said nucleotide sequence, wherein the leader sequence forms a secretion signal that is cleaved from each of said immunoglobulin light and heavy chain following proteolytic processing;
(b) isolating antigen specific immunoglobulin from the plant cells; and
(c) administering to said subject therapeutic amount of said antigen specific immunoglobulin.
53. The method of claim 52 , wherein said antibody is full length.
54. The method of claim 52 , wherein said immunoglobulin is a fragment of a full-length immunoglobulin.
55. The method of claim 52 , wherein said heavy chain includes at least a portion of a heavy chain constant region and wherein said constant region is from an IgM antibody.
56. The method of claim 52 , wherein said heavy chain includes at least a portion of a constant region and wherein said constant region is from an IgG antibody.
57. The method of claim 52 , wherein said heavy chain includes at least a portion of a constant region and wherein said constant region is from an IgA antibody.
58. The method of claim 52 , wherein said preselected antigen is from a pathogen.
59. The method of claim 58 , wherein said pathogen is selected from bacteria, viruses, or parasites.
60. The method of claim 58 , wherein said pathogen is E. Coil, Salmonellae, Vibrio cholerae , or Salmonellae typhimurium.