Anti-BCMA CAR antibodies, conjugates, and methods of use

Inventors

Friedman, Kevin • PERKINS, Molly Reed

Assignees

2Seventy Bio Inc

Abstract

The invention provides improved methods for detecting anti-BCMA CAR expression on T cells.

Core Innovation

The disclosure provides antibodies or antigen-binding fragments that bind an anti-BCMA scFv domain of an anti-BCMA CAR. The antibodies are defined by variable light chain CDRL1-CDRL3 sequences set forth in SEQ ID NOs: 1-3 or 9-11 and variable heavy chain CDRH1-CDRH3 sequences set forth in SEQ ID NOs: 4-6 or 12-14. The disclosure further describes embodiments that bind an anti-BCMA scFv epitope associated with SEQ ID NO: 25.

A defining aspect of the antibodies is that they are selectable into multiple antibody formats and binding-fragment architectures. The disclosed formats include scFv and other fragment architectures, as well as embodiments corresponding to Fab and F(ab’)2 formats, multi-specific Fab constructs, Fv/scFv variants, minibodies, diabodies/triabodies/tetrabodies, dsFv proteins, and single-domain antibodies. The disclosure also includes sequence embodiments for variable light chain and variable heavy chain components using multiple SEQ ID numbers.

The disclosure further provides labeled antibody conjugates and detectable-labeled constructs that specifically bind the anti-BCMA CAR. Detectable labels are described as selectable and include fluorescent dyes, haptens, radionuclides, and other detectable label categories. The disclosure also describes use in detecting, determining, and enumerating anti-BCMA CAR+ T cells by forming an antibody:CAR complex and measuring a signal using assays such as flow cytometry/FACS.

Claims Coverage

The independent claim covers an antibody or antigen-binding fragment defined by specific variable light-chain and variable heavy-chain CDR sequence sets that bind an anti-BCMA scFv domain of an anti-BCMA CAR. The dependent claims refine the binding target, add sequence-identification constraints, and broaden coverage to additional antibody formats and selectable labeled conjugate embodiments.

Overall, the claims cover CDR sequence-defined antibodies that bind an anti-BCMA CAR scFv domain, with refinements tied to an anti-BCMA scFv epitope (SEQ ID NO: 25) and a variable light-chain identity constraint (90% identity to SEQ ID NO: 7 or SEQ ID NO: 15). Coverage extends to selected antibody architectures and to conjugates bearing selectable fluorescent dye labels (AF350 through AF800).

Stated Advantages

Documented Applications