Trimeric binding proteins for trimeric cytokines

Abstract

The present invention pertains to the provision of trimeric binding units which bind to trimeric cytokines. In particular there is provided a trimeric polypeptide comprising a trimerising domain and three monomers with binding members capable of binding a trimeric cytokine. Preferably , the trimeric binding units bind in a manner such that upon binding, all receptor binding sites of the trimeric cytokine are substantially blocked, and hence the potential biological activity of the trimeric cytokine is suppressed. In one aspect the invention relates to trimeric binders capable of binding to trimeric cytokines of the Tumor necrosis factor ligand superfamily, such as TNF, TRAIL, RANKL, TWEAK, APRIL and BAFF.

Description

technical field [0001] The present invention provides trimeric binding proteins capable of binding trimeric cytokines. More specifically, there is provided a trimeric binder capable of binding in a manner such that after binding, substantially all receptor binding sites of said trimeric cytokine are blocked, thereby inhibiting the trimeric cytokine potential biological activity. In one aspect, the invention relates to trimeric binders capable of binding cytokines of the tumor necrosis factor ligand superfamily, including tumor necrosis factor (TNF). Background technique [0002] Cytokines are small polypeptides secreted by higher eukaryotes that are responsible for signal transduction between cells and affect the growth, division and function of other cells. They are potent, pleiotropic polypeptides which, for example via corresponding receptors, act as local or systemic intercellular regulators and thus play a key role in many biological processes, such as immunity, infla...

AI Technical Summary

Problems solved by technology

[0015] However, a common technical problem encountered with currently known trimeric cytokine conjugates and inhibitor products is that after formation of the 1:1 complex of the trimeric cytokine and the conjugate or inhibitor product, Cannot effectively block all 3 receptor binding sites of trimeric cytokines because at least 1 or 2 of the 3 receptor binding sites are still open

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