Yeda Research and Develpment & Co. Ltd

Hartmut Engelmann

David Wallach

Menachem Rubinstein

Dan Aderka

Igor Mett

Jacek Bigda

Igor Beletsky

Daniela Novick

Michel Revel

Louise Chen

Cord Brakebusch

Oliver Kemper

Yaron Nophar

An isolated DNA molecule has the sequence of encoding a fragment of encoding Tumor Necrosis Factor (TNF) Binding Protein II. It has a length sufficient to serve as an immunogen for raising antibodies against a polypeptide that is a fragment of TNF Binding Protein II. The DNA may be used to produce replicable expression vehicles and prokaryotic or eukaryotic expression host cells. Such host cells may be used to produce polypeptides encoded by such DNA molecules.

Isolated cDNA encoding tumor necrosis factor binding protein II, its purification, and vectors, hosts and processes using such cDNA

Antibodies to tumor necrosis factor receptors (TNF-Rs) are disclosed together with methods of producing them and methods of use of such antibodies in immunoassays and purification of TBP-II by affinity chromatography. A diagnostic assay for endogenous antibodies to TBP-II is also disclosed.

Methods of determining the level of human TBP-II with anti-TBP-II antibody

DNA encoding Antibodies to tumor necrosis factor receptors (TNF-Rs) are disclosed. The antibodies are preferably those which inhibit the cytotoxic effect of TNF but not its binding to the TNF-Rs. Most preferably, the antibodies bind to an extracellular domain of the C-terminal cysteine loop of the p75 TNF receptor, which loop consists of the amino acid sequence Cys-185 to Thr-201 of SEQ ID NO:3.

DNA molecule encoding TNF binding ligands and vectors and host cells containing the DNA molecule

Antibodies to Tumor Necrosis Factor receptors (TNF-Rs) which inhibit the cytocidal effect of TNF but not its binding to the TNF-Rs, and ligands interacting with other receptors of the TNF/NGF family, are provided together with methods of producing them. The antibodies preferably bind to the fourth cysteine rich domain of the p TNF receptor or to the region between said fourth cysteine rich domain and the cell membrane.

Method of inhibiting the cytocidal effect of TNF with TNF receptor-specific antibodies

Tumor necrosis factor inhibitory protein and its purification

Antibodies to Tumor Necrosis Factor receptors (TNF-Rs) which inhibit the cytocidal effect of TNF but not its binding to the TNF-Rs, and ligands interacting with other receptors of the TNF/NGF family, are provided together with methods of producing them. The antibodies preferably bind to the fourth cysteine rich domain of the p75 TNF receptor or to the region between said fourth cysteine rich domain and the cell membrane.

TNF receptor-specific antibodies

Antibodies to tumor necrosis factor receptors (TNF-Rs) are disclosed together with methods of producing them. The antibodies are preferably those which inhibit the cytotoxic effect of TNF but not its binding to the TNF-Rs. Most preferably, the antibodies bind to an extracellular domain of the C-terminal cysteine loop of the p75 TNF receptor, which loop consists of the amino acid sequence Cys-185 to Thr-201 of SEQ ID NO:3.

TNF ligands

Tumor Necrosis Factor (TNF) Inhibitory Protein is isolated and substantially purified. It has the ability to inhibit: (a) the binding of TNF to its receptors, and (b) the cytotoxic effect of TNF. TNF Inhibitory Protein and salts, functional derivatives and active fractions thereof can be used to antagonize the deleterious effects of TNF.

Tumor Necrosis Factor Binding Protein I (TBP-I), precursors and analogs thereof, are produced by transfecting eukaryotic cells with an expression vector comprising al DNA molecule encoding the whole human type I TNF receptor or a soluble domain thereof, and culturing the transfected cells, whereby the soluble proteins are secreted into the medium.

Expression of the recombinant tumor necrosis factor binding protein I

Tumor Necrosis Factor (TNF) Inhibitory Protein is isolated and substantially purified and the DNA that encodes the TNF inhibitory protein, vectors, host cells, and a recombinant method for producing the encoded protein are also set forth. It has the ability to inhibit: (a) the binding of TNF to its receptors, and (b) the cytotoxic effect of TNF. TNF Inhibitory Protein and salts, functional derivatives and active fractions thereof can be used to antagonize the deleterious effects of TNF.

DNA that encodes a tumor necrosis factor inhibitory protein and a

Human natural IFN-.beta.2/IL-6 receptor and its soluble extracellular fragment are provided in substantially purified form and are shown to stimulate and to enhance beneficial effects of IFN-.beta.2/IL-6, such as its antiproliferative activity. Polyclonal and monoclonal antibodies raised against the soluble fragment of the receptor are also provided.

Soluble IFN-.beta.2/IL-6 binding protein its preparation, and

Antibodies to TNF Binding Protein I (TBP-I) are provided that can be used in diagnostic assays and as pharmaceutical agents for either inhibiting or mimicking the effects of TNF on cells.

Growing community of inventors

Munich, Germany

Hartmut Engelmann