Centre National De La Recherche Scientifique

Vib Vzw

Universiteit Gent

Centre Hospitalier Régional Universitaire De Montpellier

Universitè De Montpellier

Universite Montpellier 2

Université Pierre Et Marie Curie (paris 6)

Univeriteit Gent

Université Pierre Et Marie Curie

Gilles Uze

Jan Tavernier

Jennyfer Bultinck

Frank Peelman

Yann Bordat

Franciane Paul

Sarah Gerlo

Genevieve Garcin

Lennart Zabeau

Etienne Simon-Loriere

Valérie Vivet-Boudou

Matteo Negroni

Sarah Gallois-Montbrun

Paola Rossolillo

Vincenzo Di Bartolo

Jose Van Der Heyden

Roland Marquet

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.

Fusokines involving cytokines with strongly reduced receptor binding affinities

The present invention relates to a modified cytokine of the TNF superfamily, with reduced activity to its receptor, wherein said modified cytokine is specifically delivered to target cells. Preferably, said modified cytokine is a single chain variant of the TNF superfamily, even more preferably, one or more of the chains can-y one or more mutations, resulting in a low affinity to the receptor, wherein said mutant cytokine is specifically delivered to target cells. The targeting is realized by fusion of the modified cytokine of the TNF superfamily to a targeting moiety, preferably an antibody or antibody-like molecule. The invention relates further to the use of such targeted modified cytokine of the TNF superfamily to treat diseases.

Targeted modified TNF family members

The present invention relates, in part, to targeted chimeric proteins with beneficial therapeutic effects, including, for example, effects mediated by chimeric proteins which comprise modified signaling agents two or more targeting moieties. Methods of treatment and pharmaceutical compositions comprising the chimeric proteins are also provided. The present invention finds use in the treatment of various disease and disorders.

Immune-cell targeted bispecific chimeric proteins and uses thereof

The present invention relates to a fusion protein, comprising a cytokine antagonist and a targeting moiety, preferably an antibody or anti-body like molecule. In a preferred embodiment, the cytokine antagonist is a modified cytokine which binds to the receptor, but doesn't induce the receptor signalling. The invention relates further to a fusion protein according to the invention for use in treatment of cancer and immune- or inflammation-related disorders.

Targeting of human interferon antagonists

The present invention relates to a modified cytokine of the TNF superfamily, with reduced activity to its receptor, wherein said modified cytokine is specifically delivered to target cells. Preferably, said modified cytokine is a single chain variant of the TNF superfamily, even more preferably, one or more of the chains carry one or more mutations, resulting in a low affinity to the receptor, wherein said mutant cytokine is specifically delivered to target cells. The targeting is realized by fusion of the modified cytokine of the TNF superfamily to a targeting moiety, preferably an antibody or antibody-like molecule. The invention relates further to the use of such targeted modified cytokine of the TNF superfamily to treat diseases.

The present disclosure relates to a modified Interleukin-1 (IL-1) family member cytokine, with reduced activity via its cytokine receptor, wherein said interleukin-1 family member cytokine is specifically delivered to target cells. Preferably, the IL-1 family member cytokine is a mutant, more preferably it is a mutant IL-1 with low affinity to the IL-1 receptor, wherein said mutant IL-1 is specifically delivered to target cells. The targeting is preferably realized by fusion of the modified IL-1 family member cytokine to a targeting moiety, preferably an antibody or antibody-like molecule. The disclosure relates further to the use of such targeted modified IL-1 family member cytokine to treat diseases.

Targeted modified IL-1 family members

A method of directing evolution of a target polynucleotide of interest for obtaining variants of this target polynucleotide, a method to generate genetic variability by preparing a cell library, and a method to isolate or to screen variants of a polynucleotide or variants of a protein able to impact the phenotype of a cell or to confer a desired phenotype to target cells, and to identify theses polynucleotide variants or protein variants responsible for this phenotype are described.

Lentiviral-based vector and its use in directed evolution of genomic regions, genes and polynucleotides

Growing community of inventors

Montpellier, France

Gilles Uze