Methods and products for controlling the immune response of a mammal to glutamic acid decarboxylase

• US 6,338,850 B1
• Filed: 05/21/1996
• Issued: 01/15/2002
• Est. Priority Date: 09/21/1993
• Status: Expired due to Fees

• Current Assignee: London Health Sciences Centre
• Original Assignee: London Health Sciences Centre
• Inventors: Jevnikar, Anthony M., Stiller, Calvin R., Ma, Shengwu
• Primary Examiner(s): Chan, Christina Y.
• Assistant Examiner(s): Ewoldt, Gerald R.
• Application Number:
  US08/617,874
• Time in Patent Office: 2,065 Days
• Field of Search: 530/350, 424/185.1, 800/200, 800/288, 800/306, 800/317.2, 800/317.3, 800/317.4, 435/410, 435/411, 435/412, 435/417, 435/414
• US Class Current: 424/185.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C12N 15/8242 with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
• CPC Class Codes: C12N 15/8257 for the production of primary gene products, e.g. pharmaceutical products, interferon
• CPC Class Codes: C12N 15/8258 for the production of oral vaccines (antigens) or immunoglobulins
• CPC Class Codes: C12N 9/88 Lyases (4.)

Abstract

A method is provided for expressing a mammalian antigen in transformed plants to provide a source of plant material for oral or enteral administration to a mammal to produce tolerance to the antigen.

Claims

1. A method for suppressing or reducing the immune response of a mammal to glutamic acid decarboxylase (GAD) comprising

orally or enterally administering to the mammal an effective immunosuppressive dose of a plant tissue or a partially purified plant tissue extract containing GAD, said plant tissue or partially purified plant tissue extract being obtained from a transgenic plant expressing GAD.

2. The method of claim 1 wherein the transgenic plant is selected from the group consisting of potato, tomato, alfalfa, canola and tobacco.

3. The method of claim 1 wherein the plant tissue or partially purified plant tissue extract is selected from the group consisting of at least one plant part, an extract of total plant protein, and a partially purified plant protein preparation.

4. The method of claim 1 wherein the plant tissue or partially purified plant tissue extract is at least one plant part selected from the group consisting of leaves, stems, seeds and tubers.

5. The method of claim 1 wherein the transgenic plant is transformed with a DNA construct for transforming a plant, said construct comprising a Cauliflower Mosaic Virus Ehn-35S promoter operably linked to a DNA coding sequence and further comprising a termination sequence in proper reading frame with the DNA coding sequence, wherein the termination sequence is a nopaline synthase termination sequence and the DNA coding sequence encodes GAD.

6. The method of claim 1 wherein the mammal is a human.

7. The method of claim 6 wherein GAD is involved in the pathogenesis of autoimmune diabetes.

8. A pharmaceutical composition for suppressing or reducing the immune response of a mammal to GAD comprising

an oral or enteral dosage form comprising an effective immunosuppressive dose of a plant tissue or partially purified plant tissue extract containing GAD and a pharmaceutically acceptable carrier, said plant tissue or partially purified plant tissue extract being obtained from a transgenic plant expressing GAD.

9. A transgenic plant expressing GAD.

10. The transgenic plant of claim 9 wherein the plant is an edible plant.

11. The transgenic plant of claim 9 wherein the plant is selected from the group consisting of potato, tomato, alfalfa, canola and tobacco.

12. An edible plant material comprising a plant tissue or partially purified plant tissue extract obtained from a transgenetic plant of claim 9.

13. An edible plant material comprising a plant tissue or partially purified plant tissue extract containing GAD, said plant tissue or partially purified plant tissue extract being obtained from a transgenic plant expressing GAD.

14. A transgenic plant wherein the plant is transfected with a DNA construct comprising a Cauliflower Mosaic Virus Ehn-35S promoter operably linked to a DNA coding sequence and further comprising a termination sequence in proper reading frame with the DNA coding sequence, wherein the termination sequence is a nopaline synthase termination sequence and the DNA coding sequence encodes GAD.

15. A method for suppressing or reducing the immune response of a mammal to GAD comprising

orally or enterally administering to the mammal an effective immunosuppressive dose of a plant tissue or partially purified plant tissue extract containing an immunosuppressive fragment of GAD, said plan tissue or partially purified plant tissue extract being obtained from a transgenic plant expressing said immunosuppressive fragment of GAD.

16. The method of claim 15 wherein the mammal is a human.

17. A pharmaceutical composition for suppressing or reducing the immune response of a mammal to GAD comprising

an oral or enteral dosage form comprising an effective immunosuppressive dose of a plant tissue or partially purified plant tissue extract containing an immunosuppressive fragment of GAD and a pharmaceutically acceptable carrier, said plant tissue or partially purified plant tissue extract being obtained from a transgenic plant expressing said immunosuppressive fragment of GAD.