PD-L1-specific antibodies and methods of using the same

Inventors

Belk, Jonathan • SHARKEY, Nathan J. • Gorelik, Leonid

Assignees

Adimab LLC • Fortress Biotech Inc • Checkpoint Therapeutics Inc

Abstract

The present disclosure relates generally to antibodies and functional binding fragments thereof that bind to programmed death-ligand 1 (PD-L1). In particular, the disclosed antibodies and fragments bind to human PD-L1 and comprise novel complementary determining regions (CDRs) also disclosed herein. Finally, the present disclosure relates to administering the disclosed antibodies and fragments to subjects with cancer, thereby treating or slowing the progression or proliferation of the cancer.

Core Innovation

The disclosure describes human programmed death-ligand 1 (PD-L1)-binding anti-PD-L1 antibodies and binding fragments. The binding is defined by specified heavy-chain and light-chain CDRs, including heavy-chain CDRH1, CDRH2, and CDRH3, and light-chain CDRL1, CDRL2, and CDRL3 defined by enumerated SEQ ID NO options.

The disclosure provides multiple named antibody variants comprising particular CDR sets, including CTI-48, CTI-57/58, CTI-09/07, and additional anti-PD-L1 antibodies (CTI-49, CTI-50, CTI-76, CTI-77, CTI-78). It characterizes these antibodies using CDR sequence sets, framework region SEQ ID selections, and variable region sequence identifiers (SEQ ID NOs), with multiple alternative CDRL3 sequences.

The disclosure further states functional properties for the disclosed PD-L1-binding antibodies, including ADCC, antitumor activity, inhibition of PD-L1:PD-1 binding, immunoblockade, and reversal of PD-1-mediated T-cell inhibition, with stated binding kinetics and binding affinity/IC50 values. It also describes optional low-fucose/defucosylated (afucosylated) glycoengineering, including Fc glycosylation modifications, as part of antibody characterization to enhance ADCC.

The stated problem is to provide antibodies or fragments that bind human PD-L1 and can be used to inhibit tumor cell proliferation and slow tumor progression by administering the disclosed anti-PD-L1 antibodies. The disclosure also outlines treatment methods for administering the antibodies alone or in combination with additional therapeutics, and it reports example assay outcomes and figures related to PD-L1 binding inhibition, binding kinetics/affinity, and functional immunological readouts.

Claims Coverage

The document includes four independent antibody-binding claims and independent method/treatment claims, each grounded on specific anti-PD-L1 CDR sequence constraints and, for some method claims, stated K_D thresholds and/or defined CDR composition using specific SEQ ID NOs. Across these independent claims, the core inventive features are PD-L1 binding defined by enumerated heavy- and light-chain CDR SEQ ID selections, optionally combined with treatment regimens and K_D thresholds.

Across the independent claims, the coverage centers on PD-L1-binding antibodies or binding fragments defined by specific heavy-chain and light-chain CDR sequence identities using enumerated SEQ ID NOs. Several independent method claims further require administration to inhibit cancer or tumor cell proliferation with specified K_D thresholds and/or specific CDRH3 region definitions, and treatment claims specify particular combinations of heavy-chain CDRH1/CDRH2/CDRH3 alternatives paired with a defined light-chain CDR set.

Stated Advantages

Documented Applications