IMMUNOSUPPRESSIVE COMBINATION AND ITS USE IN THE TREATMENT OR PROPHYLAXIS OF INSULIN-PRODUCING CELL GRAFT REJECTION

• US 20080199465A1
• Filed: 04/22/2008
• Published: 08/21/2008
• Est. Priority Date: 06/08/2001
• Status: Abandoned Application

• Current Assignee: Claudy Mullon, Philip Lake
• Original Assignee: Claudy Mullon, Philip Lake
• Inventors: Lake, Philip, Mullon, Claudy
• Application Number:
  US12/107,726
• Publication Number:
  US 20080199465A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• 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 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• 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 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

A pharmaceutical combination comprising an accelerated lymphocyte homing agent in free form or in pharmaceutically acceptable salt form, and one or more compounds selected from the group consisting of an antibody to the IL-2 receptor, an immunosuppressive macrocyclic lactone and a soluble human complement inhibitor is used to treat or prevent insulin-producing cell graft rejection.

Claims

1. A pharmaceutical combination comprising:

a) an accelerated lymphocyte homing (ALH) agent in free form or in pharmaceutically acceptable salt form; and

b) one or more compounds selected from the group consisting of an antibody to the IL-2 receptor, an immunosuppressive macrocyclic lactone and a soluble human complement inhibitor.

2. A pharmaceutical combination according to claim 1 comprising:

a) an ALH agent in free form or in pharmaceutically acceptable salt form; and

b) an antibody to the IL-2 receptor and an immunosuppressive macrocyclic lactone, and optionally a soluble human complement inhibitor.

3. A pharmaceutical combination according to claim 1 wherein the ALH agent is a compound of formula I

4. A combination according to claim 1 wherein the ALH agent is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form.

5. A combination according to claim 1 wherein the antibody to the IL-2 receptor is a recombinant chimeric or humanized antibody.

6. A combination according to claim 1 wherein the immunosuppressive macrocyclic lactone is rapamycin or a rapamycin derivative substituted in position 40 and/or 28 and/or 16, including epimers thereof, and optionally hydrogenated.

7. A combination according to claim 1 wherein the immunosuppressive macrocyclic lactone is 40-O-(2-hydroxyethyl)-rapamycin.

8. A combination according to claim 1 wherein the soluble human complement inhibitor is a C3/C5 inhibitor.

9. A pharmaceutical combination according to claim 2 wherein the ALH agent is a compound of formula I

10. A combination according to claim 2 wherein the ALH agent is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically salt form.

11. A combination according to claim 2 wherein the antibody to the IL-2 receptor is a recombinant chimeric or humanized antibody.

12. A combination according to claim 2 wherein the immunosuppressive macrocyclic lactone is rapamycin or a rapamycin derivative substituted in position 40 and/or 28 and/or 16, including epimers thereof, and optionally hydrogenated.

13. A combination according to claim 2 wherein the immunosuppressive macrocyclic lactone is 40-O-(2-hydroxyethyl)-rapamycin.

14. A combination according to claim 2 wherein the soluble human complement inhibitor is a C3/C5 inhibitor.

15. A method for the treatment or prophylaxis of insulin-producing cell graft rejection in an insulin-producing cell graft recipient comprising co-administering to the recipient an effective amount of an ALH agent and one or more compounds selected from the group consisting of an antibody to the IL-2 receptor, an immunosuppressive macrocyclic lactone, and a soluble human complement inhibitor.

16. A method according to claim 15 wherein the ALH agent is a compound of formula I

17. A method according to claim 15 wherein the ALH agent is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically salt form.

18. A method according to claim 15 wherein the antibody to the IL-2 receptor is a recombinant chimeric or humanized antibody.

19. A method according to claim 15 wherein the immunosuppressive macrocyclic lactone is rapamycin or a rapamycin derivative substituted in position 40 and/or 28 and/or 16, including epimers thereof, and optionally hydrogenated.

20. A method according to claim 15 wherein the immunosuppressive macrocyclic lactone is 40-O-(2-hydroxyethyl)-rapamycin.

21. A method according to claim 15 wherein the soluble human complement inhibitor is a C3/C5 inhibitor.