The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Dec. 29, 2015

Filed:

Aug. 06, 2014
Applicants:

Christoph Heusser, Oberwil, CH;

James Rush, Thalwil, CH;

Karen Vincent, Leymen, FR;

Inventors:

Christoph Heusser, Oberwil, CH;

James Rush, Thalwil, CH;

Karen Vincent, Leymen, FR;

Assignee:

Novartis AG, Basel, CH;

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A61K 39/395 (2006.01); C07K 16/28 (2006.01); A61K 39/00 (2006.01);
U.S. Cl.
CPC ...
C07K 16/2866 (2013.01); C07K 16/2878 (2013.01); A61K 2039/505 (2013.01); C07K 2317/52 (2013.01); C07K 2317/60 (2013.01); C07K 2317/71 (2013.01);
Abstract

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.


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