Ucbbiopharma Srl

Sanofi

James Philip O'Connell

John Robert Porter

Alastair Lawson

Daniel John Lightwood

Graham John Warrellow

Stephen Edward Rapecki

Boris Kroeplien

Timothy John Norman

Rebecca Jayne Munro

Tracy Lynn Arakaki

Mark Daniel Calmiano

William Ross Pitt

Alex Buntin Burgin

David Andreas Schubert

Rikki Peter Alexander

Alastair David Griffiths Lawson

Daniel Christopher Brookings

David James McMillan

Rebecca Jayne Wootton

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

Methods of use of anti-TNFα antibodies

A new, stable trimeric TNF&#x3b1; structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF&#x3b1;/TNFR1 interaction. Membrane-bound TNF&#x3b1; is not affected in its ability to signal through TNFR2, and thus the new structure of TNF&#x3b1; may be used in therapies which do not significantly raise the risk of infection or malignancy.

Method of identifying potential inhibitors of APO TNF&#x3b1; trimers

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Accordingly, these compounds can be used as modulators of TNF. A new assay for identifying compounds with this mechanism of action is also disclosed.

Method for identifying a modulator of the TNF&#x3b1; or CD40L interaction with their cognate receptors

Antibody against trimeric TNF&#x3b1; complex

Antibodies binding to trimeric TNF alpha epitopes

Complexes between anti-TNF antibodies, trimeric TNF proteins and organic molecules binding them

The invention is in the field of TNF signalling. Compounds have been identified which are capable of modulating signalling of TNF trimers through receptors. Methods of identifying such compounds are therefore provided. The compounds themselves have utility in therapy.

Methods of identifying signaling modulators of the trimeric TNFa

Treatment of autoimmune and inflammatory disorders with asymmetric TNF alpha trimers

TNF receptor signaling modulator assay

Growing community of inventors

Slough, United Kingdom

James Philip O'Connell