Regulatory T cell epitopes, compositions and uses thereof

• US 7,884,184 B2
• Filed: 01/29/2008
• Issued: 02/08/2011
• 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.
• Primary Examiner(s): Juedes; Amy E
• Application Number:
  US12/021,832
• Publication Number:
  US 20090018067A1
• Time in Patent Office: 1,106 Days
• Field of Search: None
• US Class Current: 530/324
• 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. An isolated T-cell epitope polypeptide consisting of the sequence of SEQ ID NO:

5.

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

3. The pharmaceutical composition of claim 2 further comprising an effective amount of an antigen or allergen.

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

(a) providing a biological sample from a subject;

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

(c) contacting the isolated regulatory T-cells with an effective amount of the T-cell epitope polypeptide of claim 1 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.

5. 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

(c) contacting the isolated regulatory T-cells with an effective amount of the T-cell epitope polypeptide of claim 1 under conditions wherein the T-regulatory cells are stimulated,

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

6. A method of suppressing an antigen-specific immune response to a target antigen in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising the T-cell epitope polypeptide of claim 1, wherein the T-cell epitope polypeptide is either covalently bound, non-covalently bound or in admixture with the target antigen resulting in the diminution of immune response against the target antigen.

7. The method of claim 6, wherein the suppressive effect is mediated by natural Treg.

8. The method of claim 6, wherein the suppressive effect is mediated by adaptive Treg.

9. The method of claim 6, wherein the suppresses T cell epitope polypeptide an effector T cell response.

10. The method of claim 6, wherein the suppresses T cell epitope polypeptide a helper T cell response.

11. The method of claim 6, wherein the suppresses T cell epitope polypeptide a B cell response.

12. A kit for repressing an antigen specific immune response in a subject, wherein the kit comprises a T-cell epitope polypeptide consisting of the sequence of SEQ ID NO:

5.

13. The kit of claim 12, further comprising an effective amount of an antigen or allergen.