08349332 is referenced by 26 patents and cites 126 patents.

Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKKα/β and IκBα, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

Title
Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases
Application Number
13/86786
Publication Number
8349332 (B2)
Application Date
April 14, 2011
Publication Date
January 8, 2013
Inventor
Edmund A Rossi
Woodland Park
NJ, US
David M Goldenberg
Mendham
NJ, US
Chien Hsing Chang
Dowingtown
PA, US
Agent
Richard A Nakashima
Assignee
IBC Pharmaceuticals
NJ, US
IPC
C12P 21/08
C07K 16/46
C07K 16/28
A61K 39/44
A61K 39/00
A61K 39/395
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