Universitãt Stuttgart

Oncomatryx Biopharma, S.l.

Biontech Ag

Universitaet Stuttgart

Baliopharm Ag

Fraunhofer-gesellschaft Zur Foerderung Der Angewandten Forschung E.v.

Biontech Rna Pharmaceuticals Gmbh

Tron—translationale Onkologie an Der Universitatsmedizin Der Johannes Gutenberg-universitat Mainz Ggmbh

Tron-translationale Onkologie an Der Universitatsmedizin Der Johannes Gutenberg-universitat Mainz

Baliopharma Ag

Universitat of Stuttgart

Biotech Rna Pharmaceuticals Gmbh

Tron—translationale Onkologie an Der Universitátsmedizin Der Johannes Gutenberg—universität Mainz Gemeinnützige Gmbh

Pfizenmaier, Klaus

Wajant, Harald

Klaus Pfizenmaier

Roland Kontermann

Martin Siegemund

Peter Scheurich

Ugur Sahin

Andreas Herrmann

Laureano Simon

Myriam Fabre

Roman Fischer

Cristina Ferrer

Sebastian Kreiter

Friederike Gieseke

Dieter Moosmayer

Dafne Müller

Kirstin Zettlitz

Harald Wajant

Thomas Wuest

Ronald Backer

Herwig Brunner

Thomas Schiestel

Meike Hutt

Matthias Grell

Ingo Grunwald

Oliver Seifert

Fabian Richter

Günter Tovar

Angela Hammer

Heike Bantel

Sina Fellermeier

Sina Fellermaier

Sabine Muenkel

Anja Krippner-Heidenreich

Sabine Münkel

Thomas Wüest

The present invention relates to polypeptide consisting of three TNF homology domains of TNF-ligand family members proteins (THD) that specifically bind to the extracellular part of TNFR2, wherein C-terminal and N-terminal reference points are defined by consensus sequences. The THIDs are linked by short stretches of further C-terminal and/or N-terminal amino acids of the THD or variants thereof as well as by peptide linkers. These peptides have an improved stability. Furthermore the invention relates to polypeptide multimers comprising several of the polypeptides of the present invention.

TNFR2 agonists with improved stability

The present invention relates to a tumor necrosis factor receptor (TNFR) binding protein complex comprising 12 or more N protein ligands (PLs) that specifically bind to the extracellular part of the same TNFR. Preferably, the TNFR binding protein complex binds to the extracellular part of TNFR2. Preferably, the TNFR binding protein complex of the present invention further comprises a two or more polymerization domains (PD).

Tumor necrosis factor receptor (TNFR) binding protein complex with improved binding and bioactivity

The present invention relates to a tumor necrosis factor receptor (TNFR) binding protein complex comprising 12 or more protein ligands (PLs) that specifically bind to the extracellular part of the same TNFR. Preferably, the TNFR binding protein complex binds to the extracellular part of TNFR2. Preferably, the TNFR binding protein complex of the present invention further comprises two or more polymerization domains (PD).

An antibody specifically recognizing human tumor necrosis factor 1 (hu TNFR1), for use in treating nonalcoholic steatohepatitis (NASH) and disease conditions associated thereto.

Method of treating nonalcoholic steatohepatitis by administering an antagonist human tumor necrosis factor receptor 1 (HUTNFR1) antibody

The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I:A-(L-D)p&#x2003;&#x2003;(I)or a pharmaceutically acceptable salts or solvates thereof,wherein:A is an antibody that selectively binds FAP;L is a linker;D is a drug comprising a cytolysin or a Nigrin-b A-chain; andp is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

Antibody-drug conjugates and immunotoxins

The present invention relates to cytokine fusion proteins and to nucleic acid molecules encoding such cytokine fusion proteins. The present invention further relates to cells, non-human organisms. pharmaceutical compositions and kits comprising the cytokine fusion proteins or the nucleic acid molecules encoding them, as well as to their use as medicaments.

Nucleic acid molecules encoding cytokine fusion proteins comprising tumor necrosis factor (TNF) superfamily ligands

The invention provides for an inhibitor of the huTNFRI receptor which is a human or humanized antibody construct that monovalently recognizes huTNFRI through an antigen-binding moiety, which is characterized by specific CDR sequences, a pharmaceutical preparation thereof, method of producing the inhibitor and the medical use of the inhibitor.

Monovalent anti-huTNFR1 antibodies, encoding nucleic acids thereof and methods of treatment thereof

The present invention relates in general to the field of TNF ligand family members. In more detail the present invention relates to polypeptides comprising at least three components A, each of which comprises the sequence of a TNF homology domain (THD) of a TNF ligand family member, or a functional derivative thereof, and comprising at least one component B consisting of a Vregion and a Vregion linked directly to each other with a linker sequence L which has a length of &#x3c;12 amino acids. Furthermore, the present invention also relates to nucleic acids encoding such polypeptides and pharmaceutical compositions thereof.

Recombinant TNF ligand family member polypeptides with antibody binding domain and uses thereof

The present invention relates to a polypeptide comprising a component A with at least three tumor necrosis factor (TNF) homology domains of TNF-ligand family members (THD) in which C-terminal and N-terminal reference points are defined by consensus sequences and which are connected through short stretches of additional C-terminal and/or N-terminal amino acids of the THD or variants thereof, and a component B comprising a dimerization domain. Further, the present invention relates to a polypeptide comprising at least three THDs in which C-terminal and N-terminal reference points are defined by consensus sequences and which are connected through short stretches of additional C-terminal and/or N-terminal amino acids of the THD or variants thereof. Further, the invention relates to a nucleic acid comprising said polypeptides, a vector comprising said nucleic acid and a pharmaceutical composition comprising said polypeptides, or said nucleic acids or said vector. Further, the present invention relates to said polypeptides, said nucleic acid or said vector for the use as a medicament or for the use in the diagnosis, prophylaxis or treatment of hyperproliferative disorders and inflammatory disorders.

Single-chain tumor necrosis factor (TNF) ligand family molecules, fusion proteins and derivatives thereof

Cytokine fusion proteins

The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I: A-(L-D)p (I) or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds FAP; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I: A-(L-D)p (I) or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds Endoglin; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

Subject matter of the invention are antibody-cytokine fusion proteins having proapoptotic and immune modulating properties, but wherein the cytokine moiety a priori has a bioactivity which is very low or restricted to certain receptor subtypes. These reagent exert their full biological activity via the corresponding cytokine receptor(s) only after antibody-mediated binding of the fusion protein to a specific cell membrane-expressed target molecule. By suitable choice of the antibody specificity, the cytokine activity is directed to the tissue, e.g. tumour tissue, to be treated, and a therapeutic agent can be produced being specifically designed/optimised for the respective indication/tumour entity.

Site-specific antibody-mediated activation of proapoptotic cytokines: AMAIZe (antibody-mediated apoptosis inducing cytokines)

Recombinant TNF ligand family member polypeptides with antibody binding domain and uses therefor

The present invention relates to a ligand, which specifically binds to human tumor necrosis factor type 1 receptor (huTNFR1). The ligand includes one or more amino acid sequences of human origin capable of reducing the immunogenic response of the ligand in humans and one or more amino acid sequences capable of selectively binding to huTNFR1. The present invention also relates to a nucleic acid sequence encoding the ligand and to a pharmaceutical composition for the treatment of disorders related to huTNFR1.

huTNFR1 selective antagonists

Growing community of inventors

Tiefenbronn, Germany

Klaus Pfizenmaier