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Identification of Potent Human anti-IL-1RI Antagonist Antibodies

Identification of Potent Human anti-IL-1RI Antagonist Antibodies

Zoey L Fredericks, Carla Forte, Irene V Capuano, Hongxing Zhou, Tim Vanden Bos, Paul Carter

Protein Eng Des Sel. 2004 Jan;17(1):95-106.

PMID: 14985542

Abstract:

Interleukin-1 (IL-1) blockade by IL-1 receptor antagonist benefits some arthritis patients by reducing joint damage. This fact inspired us to develop antagonist human therapeutic antibodies against IL-1R(I) using phage libraries that display single-chain variable fragment (scFv) antibody fragments. Panning libraries against human IL-1R(I) generated 39 unique scFv-phage whose binding to IL-1R(I) was competed by IL-1 ligands. Fifteen of these scFv-phage, identified using IL-1R(I)-binding assays and dissociation rate ranking, were reformatted as scFv-Fc and IgG(4) molecules. The ease of producing antibodies in the scFv-Fc format permitted rapid identification of four lead clones (C10, C13, C14, C15) that inhibit NF-kappaB nuclear translocation induced by IL-1. Reformatting these clones as IgG(4) molecules increased their inhibition potency by

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413333	IL-1 Receptor Type I (human): FC (human)			Price

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