The Mathilda and Terence Kennedy Institute of Rheumatology

Richard Neve

Marc Feldmann

Yuti Chernajovsky

The present invention relates to a receptor molecule which binds to TNF comprising all or a functional portion of the extracellular domain (ECD) of two or more TNF-Rs linked via one or more polypeptide linkers. The receptor can further comprise a signal peptide of a secreted protein, such as the signal peptide of the extracellular domain of the TNF-R or the signal peptide of a cytokine. The invention also relates to isolated DNA encoding a receptor molecule which binds to TNF, comprising two or more sequences encoding all or a functional portion of the ECD of TNF-Rs linked via one or more sequences encoding a polypeptide linker. The invention further relates to a method of making a construct which expresses all or a functional portion of the ECD of two or more TNF-Rs linked via one or more polypeptide linkers and cells which express the construct. The invention also relates to a method of inhibiting the biological activity of TNF in a host comprising administering to the host an effective amount of a receptor molecule of the present invention. The invention further relates to receptor molecules which bind cytokines that bind to receptor molecules comprising more than one subunit.

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Sandwich, United Kingdom

Richard Neve