Fusokines involving cytokines with strongly reduced receptor binding affinities

• US 10,640,542 B2
• Filed: 07/03/2014
• Issued: 05/05/2020
• Est. Priority Date: 07/18/2013
• Status: Active Grant

• Current Assignee: Centre Hospitalier Régional Universitaire de Montpellier, Centre National De La Recherche Scientifique, Universiteit Gent Vzw, VIB VZW
• Original Assignee: VIB VZW
• Inventors: Tavernier, Jan, Bultinck, Jennyfer, Gerlo, Sarah, Uze, Gilles, Paul, Franciane, Bordat, Yann
• Primary Examiner(s): Weiler, Karen S.
• Assistant Examiner(s): Hissong, Bruce D.
• Application Number:
  US14/905,343
• Publication Number:
  US 20180155404A1
• Time in Patent Office: 2,133 Days
• CPC Class Codes: A61K 38/195 Chemokines, e.g. RANTES
• CPC Class Codes: A61K 38/2006 IL-1
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/521 Chemokines
• CPC Class Codes: C07K 14/523 Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1, LDCF-2
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/545 IL-1
• CPC Class Codes: C07K 14/56 IFN-alpha
• CPC Class Codes: C07K 14/5759 Products of obesity genes, e.g. leptin, obese (OB), tub, fat
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/74 containing a fusion for binding to a cell surface receptor

Abstract

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

Claims

1. A composition comprising a fusion protein comprising at least two cytokines, wherein the cytokines are CC chemokine 20 (CCL20) and mutant human interleukin-1 beta (IL-1β

) and wherein IL-1β

comprises a mutation selected from R120G, Q131G, H146A, and Q148G that reduces binding activity of IL-1β

to its receptor as compared to wild type IL-1β

, and the CCL20 is wild-type and provides cell-specific targeting that restores activity of the mutant IL-1β

on the targeted cells.

2. The composition of claim 1, further comprising a GGS linker.

3. The composition of claim 1, wherein the human IL-1β

mutation is Q148G.

4. The composition of claim 1, wherein the human IL-1β

mutation is R120G.

5. The composition of claim 1, wherein the human IL-1β

mutation is Q131G.

6. The composition of claim 1, wherein the human IL-1β

mutation is H146A.