RAPAMYCIN AND IL-10 FOR THE TREATMENT OF IMMUNE DISEASES

• US 20080069797A1
• Filed: 08/16/2007
• Published: 03/20/2008
• Est. Priority Date: 11/29/2002
• Status: Active Grant

• Current Assignee: Tr1X, Inc.
• Original Assignee: Maria Grazia Ronocarlo
• Inventors: RONCAROLO, Maria, BATTAGLIA, Manuela
• Granted Patent: US 8,329,637 B2
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/1777 Integrin superfamily
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 16/289 : against CD45
• CPC Class Codes: C07K 2317/626 : Diabody or triabody
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The invention discloses a combined preparation containing IL-10 and rapamycin, able to induce immunosuppression and antigen-specific immune tolerance, and the use thereof in the treatment of diseases involving an excessive, dysfunctional or uncontrolled immune responses mediated by T cells.

Claims

1. A method for inducing antigen-specific immune tolerance in a subject affected by a disease involving an excessive, dysfunctional or uncontrolled self- or non-self T cell mediated immune response, comprising administering to said subject an effective amount IL-10 and rapamycin, or an analog, derivative or conjugate thereof.

2. The method according to claim 1, wherein said disease is selected from the group consisting of allogenic organ rejection, allograft b-islets rejection, graft versus host disease, type I diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus erithematosus;

chronic inflammatory disease;

Crohn'"'"'s disease and ulcerative colitis;

chronic obstructive pulmonary diseases;

allergic disease selected from asthma and atopic dermatitis;

fibrotic diseases; and

immune reactions to gene therapy.

3. The method according to claim 1, wherein IL-10 is of human or viral origin.

4. The method according to claim 3, wherein IL-10 is conjugated to polyethyleglycol (PEG).

5. The method according to claim 1, wherein the antigen-specific immune tolerance is mediated by Tr1 cells and/or CD4+CD25+ Tr cells.

6. The method according to claim 1, wherein IL-10 and rapamycin are contained in a pharmaceutical preparation suitable for the oral, intravenous, parenteral or subcutaneous administration.

7. The method according to claim 6, wherein said pharmaceutical preparation is in the form of a solution, suspension, tablet or capsule.

8. The method according to claim 6, wherein IL-10 and rapamycin are simultaneously, separately or sequentially administered to said subject.

9. The method according to claim 1, further comprising administering to the subject an active substance which is selected from the group consisting of cyclosporine, FK506, pimecrolimus, mycofenolate and antibodies against CD45,LFA-1 molecules and IL-2 receptor.

10. The method according to claim 1, wherein the effective wherein the effective amount of IL-10 is from 0.001 μ

g/kg to 1000 μ

g/kg and the effective amount of rapamycin is from 0.001 mg/kg to 100 mg/kg.

11. The method according to claim 1, wherein said disease is an autoimmune disease.