REGULATORY T CELL EPITOPES, COMPOSITIONS AND USES THEREOF

• US 20090018067A1
• Filed: 01/29/2008
• Published: 01/15/2009
• Est. Priority Date: 01/30/2007
• Status: Active Grant

• Current Assignee: EpiVax, Inc.
• Original Assignee: EpiVax, Inc.
• Inventors: Martin, William, De Groot, Anne, Rivera, Daniel S.
• Granted Patent: US 7,884,184 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• 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: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/47 : from mammals
• CPC Class Codes: C07K 14/75 : Fibrinogen
• CPC Class Codes: C07K 14/76 : Albumins
• CPC Class Codes: C07K 14/78 : Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 14/79 : Transferrins, e.g. lactoferrins, ovotransferrins

Abstract

The invention is directed to T cell epitopes wherein said epitopes comprises a peptide or polypeptide chain comprising at least a portion of an immunoglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.

Claims

1. A T-cell epitope polypeptide composition comprising at least one polypeptide selected from the group consisting of:

SEQ ID NOS;

4-58.

5. A pharmaceutical composition comprising the T-cell epitope polypeptide composition of claim 1 and a pharmaceutically acceptable carrier.

2. A nucleic acid encoding at least one T-cell epitope polypeptide selected from the group consisting of:

SEQ ID NOS;

4-58.

3. A vector comprising the nucleic acid according to claim 2.

4. A cell comprising the vector according to claim 3.

6. A method of treating or preventing a medical condition in a subject in need thereof comprising administering a therapeutically effective amount of a T-cell epitope polypeptide selected from the group consisting of:

SEQ ID NOS;

4-58.

7. The method according to claim 6, wherein the medical condition is selected from the group consisting of:

an allergy, an autoimmune disease, a transplant related disorder, graft versus host disease, an enzyme or protein deficiency disorder, a hemostatic disorder, cancer, infertility; and

a viral, bacterial or parasitic infection.

8. A kit for preventing or treating a medical condition in a subject, wherein the kit comprises at least one T-cell epitope polypeptide selected from the group consisting of:

SEQ ID NOS;

4-58.

9. A method for expanding a population of regulatory T cells, comprising:

(a) providing a biological sample from a subject; and

(b) isolating regulatory T-cells from the biological sample; and

contacting the isolated regulatory T-cells with an effective amount of a Tregitope composition of the invention under conditions wherein the T-regulatory cells increase in number to yield an expanded regulatory T-cell composition,

thereby expanding the regulatory T-cells in the biological sample.

10. A method for stimulating regulatory T cells in a biological sample, comprising:

(a) providing a biological sample from a subject;

(b) isolating regulatory T-cells from the biological sample; and

contacting the isolated regulatory T-cells with an effective amount of a Tregitope composition of the invention under conditions wherein the T-regulatory cells are stimulated to alter one or more biological function,

thereby stimulating the regulatory T-cells in the biological sample.

11. A method for repressing immune response in a subject, comprising administering a composition comprising a therapeutically effective amount of a peptide comprising a Tregitope to the subject, wherein the peptide represses the immune response.

12. The method of claim 11, wherein the peptide suppresses effector T cell response.

13. The method of claim 11, wherein the peptide suppresses helper T cell response.

14. The method of claim 11, wherein the peptide suppresses B cell response.

15. A method of suppressing antigen-specific immune response in a subject through the administration of a therapeutically effective amount of a composition comprising one or more Tregitopes, wherein the one or more Tregitopes are either covalently bound, non-covalently bound or in admixture with a specific target antigen resulting in the diminution of immune response against the target antigen.

16. The method of claim 15, wherein the suppressive effect is mediated by natural Treg.

17. The method of claim 15, wherein the suppressive effect is mediated by adaptive Treg.

18. The method of claim 15, wherein the peptide suppresses effector T cell response.

19. The method of claim 15, wherein the peptide suppresses helper T cell response.

20. The method of claim 15, wherein the peptide suppresses B cell response.

21. The method of claim 15, wherein the peptide comprises a sequence selected from the group consisting of:

SEQ ID NOS;

4-58.

22. A method for enhancing the immunogenicity of a vaccine delivery vector, comprising identification and removal of regulatory T cell epitopes.

23. The method of claim 22, wherein the T cell epitopes are selected from the group consisting of:

SEQ ID NOS;

4-58.