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AssigneeWilliam Robert Arathoon Living Trust Dated August 29, 2016
InventorsWilliam Robert Arathoon, Mastewal Abuhay, Raffaella Briante, Alissa Loren O'Connor, Paul David Ponath, Cindy Tan, Qianting Zhai, Pingping Zhang
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Provided are anti-ABCB 1 antibodies that may be used as multi-specific, including bispecific, antibodies targeting both ABCB 1 and a tumor-associated antigen (TAA), as well as pharmaceutical compositions, nucleic acids, recombinant expression vectors, cells, and kits that include or encode such antibodies and multi-specific antibodies. Further included are uses and methods of treating conditions where inhibition of ABCB 1-mediated efflux transport is desirable, such as, cancer or multi-drug resistance mediated by the ABCB1 transporter, e.g., multi-drug resistant cancer. In particular, the disclosure provides humanized multi-specific, e.g. bispecific, IgG (IgG1) antibodies that bind ABCB1 and a TAA. Multi-specific IgG1 antibody molecules are provided with Fc substitutions in at least one of a first and a second heavy chain constant region.
A multi-specific IgG1 antibody molecule comprising a first heavy chain that comprises an antigen-binding site for multidrug resistance protein 1 (ABCB1) and a second heavy chain that comprises an antigen-binding site for a tumor associated antigen (TAA) each heavy chain comprising an Fc region, wherein one of the Fc regions comprises hole amino acid substitutions Y349C, T366S, L368A, and Y407V, in combination with amino acid substitution F405V or Q347R, wherein numbering is according to the EU numbering scheme.
A bispecific humanized IgG1 antibody molecule that binds multidrug resistance protein 1 (ABCB1) and a tumor associated antigen (TAA), the antibody molecule comprising two identical light chain variable regions, a first heavy chain variable region, and a second heavy chain variable region,
The bispecific humanized IgG1 antibody molecule according to 30 wherein said Fc region further comprises amino acid substitution F405V or Q347R.
A humanized antibody light chain binding to ABCB1 comprising CDRs 1-3 (LCDRs 1-3) of a light chain variable region sequence selected from the group consisting of:
Dependencies are inferred from the claim text.