公开(公告)号：WO2016202412A1

公开(公告)日：2016-12-22

申请号：PCT/EP2015074491

申请日：2015-10-22

Applicant: UCB BIOPHARMA SPRL

Inventor： O'CONNELL JAMES PHILIP ,  PORTER JOHN ROBERT ,  LAWSON ALASTAIR ,  KROEPLIEN BORIS ,  RAPECKI STEPHEN EDWARD ,  NORMAN TIMOTHY JOHN ,  WARRELLOW GRAHAM JOHN ,  ARAKAKI TRACY LYNN ,  BURGIN ALEX BUNTIN ,  PITT WILLIAM ROSS ,  CALMIANO MARK DANIEL ,  SCHUBERT DAVID ANDREAS ,  LIGHTWOOD DANIEL JOHN ,  WOOTTON REBECCA JAYNE

IPC: G01N33/68 ,  C07D401/14 ,  C07D471/00 ,  C07K14/525 ,  C07K14/705

CPC classification number: G01N33/6845 ,  C07D401/14 ,  C07D471/00 ,  C07K14/525 ,  C07K14/70575 ,  C07K16/241 ,  G01N2500/02

Abstract: A new, stable trimeric TNFα 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 TNFα/TNFR1 interaction. Membrane-bound TNFα is not affected in its ability to signal through TNFR2, and thus the new structure of TNFα may be used in therapies which do not significantly raise the risk of infection or malignancy.

Abstract translation: 公开了一种新的稳定的三聚体TNFα结构，其具有扭曲的对称性，其可以结合TNFR1受体以减弱其信号传导，其可用于治疗和/或预防与可溶性TNFα/ TNFR1相互作用相关的疾病。 膜结合的TNFα在其通过TNFR2信号的能力方面不受影响，因此TNFα的新结构可用于不显着升高感染或恶性肿瘤风险的疗法。

公开(公告)号：ES2836769T3

公开(公告)日：2021-06-28

申请号：ES15784066

申请日：2015-10-22

Applicant: UCB BIOPHARMA SPRL

Inventor： O'CONNELL JAMES PHILIP ,  PORTER JOHN ROBERT ,  LAWSON ALASTAIR ,  KROEPLIEN BORIS ,  RAPECKI STEPHEN EDWARD ,  NORMAN TIMOTHY JOHN ,  MCMILLAN DAVID JAMES ,  WARRELLOW GRAHAM JOHN ,  BROOKINGS DANIEL CHRISTOPHER ,  ALEXANDER RIKKI PETER

IPC: G01N33/68 ,  C07D401/14 ,  C07D471/00 ,  C07K14/525 ,  C07K14/705

Abstract: Un método de identificación de un compuesto que es capaz de unirse a una proteína trimérica que es un miembro de la superfamilia del factor de necrosis tumoral (TNF) y modular la señalización de la proteína trimérica a través del receptor de la superfamilia del TNF necesario, comprendiendo el método determinar el número promedio de receptores unidos por cada complejo trímero-compuesto y, de este modo, identificar si el compuesto es capaz de modular la señalización a través del receptor.

公开(公告)号：CA2988516A1

公开(公告)日：2016-12-22

申请号：CA2988516

申请日：2015-10-22

Applicant: UCB BIOPHARMA SPRL

Inventor： O'CONNELL JAMES PHILIP ,  PORTER JOHN ROBERT ,  LAWSON ALASTAIR ,  KROEPLIEN BORIS ,  RAPECKI STEPHEN EDWARD ,  NORMAN TIMOTHY JOHN ,  WARRELLOW GRAHAM JOHN ,  ARAKAKI TRACY LYNN ,  BURGIN ALEX BUNTIN ,  PITT WILLIAM ROSS ,  CALMIANO MARK DANIEL ,  SCHUBERT DAVID ANDREAS ,  LIGHTWOOD DANIEL JOHN ,  WOOTTON REBECCA JAYNE

IPC: G01N33/68 ,  C07D401/14 ,  C07D471/00 ,  C07K14/525 ,  C07K14/705

Abstract: A new, stable trimeric TNFa 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 TNFa/TNFR1 interaction. Membrane-bound TNFa is not affected in its ability to signal through TNFR2, and thus the new structure of TNFa may be used in therapies which do not significantly raise the risk of infection or malignancy.

公开(公告)号：CA2987823A1

公开(公告)日：2016-12-22

申请号：CA2987823

申请日：2015-10-22

Applicant: UCB BIOPHARMA SPRL

Inventor： O'CONNELL JAMES PHILIP ,  PORTER JOHN ROBERT ,  LAWSON ALASTAIR ,  KROEPLIEN BORIS ,  RAPECKI STEPHEN EDWARD ,  NORMAN TIMOTHY JOHN ,  MCMILLAN DAVID JAMES ,  WARRELLOW GRAHAM JOHN ,  BROOKINGS DANIEL CHRISTOPHER ,  ALEXANDER RIKKI PETER

IPC: G01N33/68 ,  C07D401/14 ,  C07D471/00 ,  C07K14/525 ,  C07K14/705

Abstract: 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.

公开(公告)号：CA2987827A1

公开(公告)日：2016-12-22

申请号：CA2987827

申请日：2015-10-22

Applicant: UCB BIOPHARMA SPRL

Inventor： O'CONNELL JAMES PHILIP ,  PORTER JOHN ROBERT ,  LAWSON ALASTAIR ,  KROEPLIEN BORIS ,  RAPECKI STEPHEN EDWARD ,  NORMAN TIMOTHY JOHN ,  WARRELLOW GRAHAM JOHN

IPC: G01N33/68 ,  C07D401/14 ,  C07D471/00 ,  C07K14/525 ,  C07K14/705

Abstract: 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. Anew assay for identifying compounds with this mechanism of action is also disclosed.