Novartis Ag

James Rush

Christoph Heusser

Karen Vincent

Pascal Espie

Boerje Haraldsson

Peter Gergely

Grazyna Wieczorek

Lukas Roth

Christian Loesche

The disclosure relates to methods, treatment regimens, uses, kits and therapies for treating hidradenitis suppurativa, by employing CD40 antagonists, such as anti-CD40 antibodies.

Anti-CD40 antibodies for use in treatment of hidradenitis suppurativa

The disclosure relates to methods, treatment regimens, uses, kits and therapies for treating Sjögren's syndrome, by employing anti-CD40 antibodies.

Anti-CD40 antibodies for use in treatment of Sjögren's syndrome

The disclosure relates to methods, treatment regimens, uses, kits and therapies for preventing graft rejection in solid organ transplantation, by employing anti-CD40 antibodies.

Anti-CD40 antibodies for use in prevention of graft rejection

The present invention relates to silent Fc variants of anti-CD40 antibodies and compositions and methods of use of said antibodies for treating pathological disorders such as autoimmune and inflammatory disorders and/or for preventing or reducing the risk of graft rejection in transplantation.

Method of treating transplant rejection with silent Fc variants of anti-CD40 antibodies

Nucleic acids encoding silent Fc variants of anti-CD40 antibodies

Silent Fc variants of anti-CD40 antibodies

Anti-CD40 antibodies have not been reported to induce hemostatic events in patients, however elevations in pancreatic enzymes in B cell lymphoma patients receiving the anti-CD40 Ab Chir12.12 and the possible risk of pancreatitis precludes the use of this Fc-competent anti-CD40 antibody in chronic autoimmune disease and transplantation for safety reasons. We therefore generated Fc-silent IgG1 anti-CD40 antibodies (mAb1, mAb2 and mAb3) unable to mediate antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) both in vitro and in vivo. mAb1 was able to prolong non-human primate renal allograft survival in combination with sub-therapeutic doses of cyclosporine. In addition, mAb1 was able to completely suppress primary and secondary antibody responses to immunization with a T cell-dependent antigen. Crucially, there was no evidence of hemostatic events or abnormal pancreatic histology in either the transplant or immunization study. Collectively these results suggest mAb1 would be a safe and efficacious therapeutic, and could be used to treat patients suffering from B lymphocyte and antigen presenting cell driven autoimmune disease or undergoing allograft transplant where CD4O-CD154 interactions are involved in contributing to pathology.

Growing community of inventors

Thalwil, Switzerland

James Rush