Celltech R&d Limited

Ucb Biopharma Sprl

Celltech Therapeutics Limited

Ucbbiopharma Srl

Ucb Pharma, S.a.

Celltech Limited

Sanofi

Novartis Ag

John Robert Porter

John Clifford Head

Graham John Warrellow

Sarah Catherine Archibald

Boris Kroeplien

Victoria Elizabeth Jackson

Timothy John Norman

Julien Alistair Brown

Rikki Peter Alexander

James Andrew Johnson

James Philip O'Connell

Daniel Christopher Brookings

Alastair Lawson

Barry John Langham

Stephen Brand

Stuart Bailey

Fabien Claude Lecomte

Janeen Marsha Linsley

Daniel John Lightwood

Martin Alexander Lowe

Stephen Edward Rapecki

Rebecca Jayne Munro

Zhaoning Zhu

Thomas A Millican

Matthew Duncan Selby

Nigel Robert Beeley

Joanna Rachel Quincey

John R Morphy

Brian Woodside Hutchinson

Tracy Lynn Arakaki

Craig Johnstone

Martin Clive Hutchings

Jag Paul Heer

Jonathan Bentley

Mark Daniel Calmiano

Andrew James Ratcliffe

Michael Alan Shaw

James Madden

Catherine McKay

Jonathan Mark Bentley

James Thomas Reuberson

Helen Tracey Horsley

Gareth Neil Brace

Laura Gleave

Anne Marie Foley

Mezher Hussein Ali

William Ross Pitt

Ellen Olivia Gallimore

Alexander Heifetz

Prafulkumar Tulshibhai Chovatia

Alex Buntin Burgin

David Andreas Schubert

Thomas Paul Cain

Deborah Leigh

Laura Jane Gleave

Praful Tulshi Chovatia

Alastair David Griffiths Lawson

Terence Seward Baker

Michael Scott Visser

Pui Leng Loke

Elizabeth Pearl Jones

Naeem Yusuff

Ewan C Boyd

David James McMillan

Michael Anthony Eaton

Christopher Francis Palmer

Gregory Foulkes

Ian Yule

Pavandeep Singh Aujla

Muhammed Kamal Uddin

Michael Louis Robert Deligny

Giancarlo Trani

Severine Danielle Jones

Hervé Jean Claude Deboves

Sabine Defays

Daniel Ford

Rebecca Jayne Wootton

Ajay Mandal

Yolanda Pérez-Fuertes

Donald Smyth

Craig Miller

Darshan Gunvant Vaidya

Laura Claire Reed

Anthony John Richardson

Sarah Emily Richardson

David James Mcmillan

Michael Louis Deligny

Herve Jean Deboves

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

A series of substituted 3,4-dihydro-2H-.1,4-benzoxazin-3-one derivatives, and analogs thereof, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neuradegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. 

Substituted benzo[b][1,4]oxazines and pyrido[3,2-b][1,4]oxazines as modulators of tumor necrosis factor activity

A series of substituted 4,5,6,7-tetrahydrobenzimidazole derivatives, being potent modulators of human TNF&#x3b1; activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Tetrahydrobenzimidazole derivatives as modulators of TNF activity

A series of substituted purine derivatives, being potent modulators of human TNF&#x3b1; activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Purine derivatives as modulators of TNF activity

A series of substituted 1H imidazo[4,5-b]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. 

Imidazopyridine derivatives as modulators of TNF activity

A series of substituted 5,6,7,8-tetrahydroimidazo[1,2-&#x3b1;]pyridine derivatives, being potent modulators of human TNF&#x3b1; activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Tetrahydroimidazopyridine derivatives as modulators of TNF activity

A series of substituted imidazo[1,2-a]pyrimidine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. 

Imidazopyrimidine derivatives as modulators of TNF activity

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Slough, United Kingdom

John Robert Porter