Combination of interleukin-2 with an interleukin 1 inhibitor, conjugates and therapeutic uses thereof

Patent metadata

Field	Value
Publication number	US-12403181-B2
Application number	US-201917268030-A
Country	US
Kind code	B2
Filing date	Aug 13, 2019
Priority date	Aug 13, 2018
Publication date	Sep 2, 2025
Grant date	Sep 2, 2025

Abstract

The present invention relates to a combination of i) interleukin-2 (IL-2) and ii) an interleukin 1 (IL-1) inhibitor, for use in treating an auto-immune and/or inflammatory disorder in a subject. It is also provided a pharmaceutical composition comprising interleukin-2 (IL-2) and an interleukin-1 (IL-1) inhibitor. The invention further provides a conjugate comprising IL-2 conjugated to an IL-1 inhibitor.

First claim

The invention claimed is:

1. A method for increasing regulatory T cells and reducing inflammation in a subject in need thereof, the method comprising administering to the subject a combination of i) interleukin-2 (IL-2) and ii) an interleukin 1 (IL-1) inhibitor, wherein the IL-1 inhibitor is a recombinant IL-1Rα.

2. The method of claim 1 , wherein the recombinant IL-1Rα is anakinra.

3. The method of claim 1 , wherein the IL-2 is administered at a dose of 3.5 MIU/day or less.

4. The method of claim 3 , wherein the IL-2 is administered between 0.5 and 1.5 MIU/day.

5. The method of claim 1 , wherein the subject is a human patient having an auto-immune and/or inflammatory disorder selected from the group consisting of systemic lupus erythematosus, type I diabetes, HCV-related vasculitis, uveitis, myositis, systemic vasculitis, psoriasis, allergy, asthma, Crohn's disease, multiple sclerosis, rheumatoid arthritis, atherosclerosis, autoimmune thyroid disease, auto-inflammatory diseases, neuro-degenerative diseases, Alzheimer's disease, graft-versus-host disease, spontaneous abortion and allograft rejection; solid organ transplantation rejection, vasculitis, inflammatory bowel disease (IBD), allergic asthma, spondyloarthritis or ankylosing Spondylitis, Sjogren's syndrome, Systemic sclerosis, Alopecia aerate, and Ulcerative Colitis.

6. The method of claim 1 , wherein the IL-2 is administered sequentially with the IL-1 inhibitor.

7. The method of claim 1 , wherein the IL-2 is administered simultaneously with the IL-1 inhibitor.

8. The method of claim 7 , wherein the IL-2 and the IL-1 inhibitor are administered within the same composition.

9. The method of claim 8 , wherein the IL-2 and the IL-1 inhibitor are administered subcutaneously.

10. The method of claim 1 , wherein the IL-2 comprises a fusion protein.

11. The method of claim 10 , wherein the fusion protein comprises an IL-2 moiety and a moiety selected from the group consisting of an immunoglobulin or an immunoglobulin fragment, serum albumin, transferrin, and Fn3, or a variant thereof.

12. The method of claim 1 , wherein the IL-2 comprises an IL-2 moiety conjugated to a non-protein polymer.

13. The method of claim 12 , wherein the non-protein polymer is polyethylene glycol.

14. The method of claim 1 , wherein the IL-2 is human IL-2 or an active analogue thereof, wherein the active analogue is aldesleukin.

15. The method of claim 14 , wherein the IL-2 is human wild-type IL-2.

16. The method of claim 14 , wherein the IL-2 is aldesleukin.

17. The method of claim 1 , wherein the subject is a human subject.

Assignees

• Iltoo Pharma
• Univ Sorbonne
• Assist Publique—Hopitaux De Paris
• Inst Nat Sante Rech Med
• Inserm Institut Nat De La Sante Et De La
• Rech Medicale

Inventors

• Klatzmann David
• Mariau Jérémie
• Ritvo Paul-Gydéon
• Mariotti-Ferrandiz Encarnita
• Vazquez Thomas
• Billiald Nicolas

Classifications

• C07K16/245

  IL-1 · CPC title

• A61K38/177

  Receptors; Cell surface antigens; Cell surface determinants · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title