Anti-BCMA heavy chain-only antibodies
Inventors
Trinklein, Nathan • Aldred, Shelley Force • Clarke, Starlynn • van Schooten, Wim
Assignees
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Publication Number
US-11427642-B2
Publication Date
2022-08-30
Expiration Date
Abstract
Anti-BCMA heavy chain-only antibodies (UniAb) and disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat B-cell disorders characterized by the expression of BCMA.
Core Innovation
The disclosed invention provides anti-BCMA heavy chain-only antibodies that bind human B-Cell Maturation Antigen (BCMA). The antibodies are defined by a heavy chain variable region having a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 9, and a CDR3 sequence of SEQ ID NO: 13. The design places these CDR sequences within a human VH framework and uses a heavy chain constant region that can be provided without a CH1 sequence.
The disclosed antibody family is described with sequence-identity constraints for heavy chain variable regions, including high % identity to defined SEQ ID NOs. Representative antibody coverage includes specified heavy chain variable region sequences across SEQ ID NOs 16-50, and an example antibody designated as 308902. The invention further encompasses formats in which the heavy chain-only binding domain can be configured for multispecific or bispecific applications, including BCMA×CD3, and references use in CAR-T contexts involving a scFv and human VH and bispecific human VH CAR-T.
The invention is directed to treatment-related use cases for BCMA-expressing B-cell disorders, including multiple myeloma and systemic lupus erythematosus (SLE). Functional characterization described in the disclosure includes binding to BCMA protein and BCMA+ cell lines, and evaluation of off-target binding, including minimal off-target binding such as H929 BCMA−. The disclosure also describes BCMA-targeted blocking of APRIL/BCMA receptor binding in a recombinant assay and reports affinity measurements for antibody 308902.
Claims Coverage
The partial claim set includes two independent claim families (clm-00001 and clm-00006). Each independent claim is centered on a heavy chain-only antibody binding to human BCMA defined by the same specific CDR1/CDR2/CDR3 sequence assignments, with additional structural and framework constraints in dependent claim sets.
CDR-defined BCMA binding heavy chain-only antibody
A heavy chain-only antibody binding to human BCMA comprising a heavy chain variable region with a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 9, and a CDR3 sequence of SEQ ID NO: 13.
Human VH framework CDR-defined BCMA binding heavy chain-only antibody
A heavy chain-only antibody binding to human BCMA comprising a heavy chain variable region with a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 9, and a CDR3 sequence of SEQ ID NO: 13 in a human VH framework.
Across the independent claims, the core inventive coverage is limited to heavy chain-only antibodies that bind human BCMA and are defined by fixed CDR1/CDR2/CDR3 sequence identities (SEQ ID NO: 2, 9, and 13), with claim coverage further requiring the CDRs to be arranged in a human VH framework in one independent claim and refined by heavy-chain-only format constraints (including absence of CH1) and binding-format recast into multispecific/bispecific contexts in dependent claim sets.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of multiple myeloma.
Treatment of systemic lupus erythematosus (SLE).
Multispecific/bispecific use including BCMA×CD3.
CAR-T use involving scFv and human VH and bispecific human VH CAR-T.
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