Anti-BCMA antibodies and treatment methods
Inventors
Yam, Alice • Stafford, Ryan • Li, Xiaofan • Yang, Junhao • Armstrong, Stephanie • YU, Abigail
Assignees
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Publication Number
US-11993658-B2
Publication Date
2024-05-28
Expiration Date
Abstract
The present disclosure relates to antibodies that selectively bind to B-cell maturation antigen (BCMA) and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.
Core Innovation
The disclosure relates to isolated anti-BCMA antibodies of the IgG class that specifically bind to B-cell maturation antigen (BCMA), identified as TNFRSF17 (CD269). The antibodies are defined by six CDRs, comprising CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, corresponding to a specified VH-VL pair identified by SEQ ID NO: 170 and 217. BCMA is discussed in connection with multiple myeloma and other cancers, including leukemia and lymphoma, as well as autoimmune disease and infection contexts.
The specification defines antibody formats including IgG1, IgG2, IgG3, and IgG4, and antibody fragments including Fv, Fab, F(ab’)2, Fab’, scFv, and scFv-Fc. The disclosure also describes CDRs using Kabat numbering scheme and Chothia numbering scheme, including illustrative CDR lengths and allowable CDR sequence variants. The selection of anti-BCMA antibody heavy-chain/light-chain variable pairs includes specified VH sequences and VL sequences, with variants having high sequence identity and limited amino-acid changes using conservative substitutions.
The patent further specifies the pairing of VH-VL and multi-CDR combinations that maintain binding to human BCMA and related isoforms/homologs. Binding and association parameters are included in the definition, including affinity (KD, ka, kd) and binding characterized by association (ka). The description also characterizes BCMA-binding antibodies across multiple antibody formats and species-targeted formats, including Fab-HC/TM2 formats and human/cyno BCMA-Fc.
Claims Coverage
The claim coverage centers on one independent claim defining an isolated IgG-class antibody that specifically binds BCMA using six specified CDRs derived from a defined VH-VL pairing (SEQ ID NO: 170 and 217). The dependent and related claim features further refine this scope with specified VH and VL variants, particular CDR sequences, binding association characteristics, and an administering-based treatment claim for BCMA-expressing cancer.
IgG-class anti-BCMA antibody with defined six CDRs from a VH-VL pair
An isolated IgG-class antibody that specifically binds B-cell maturation antigen (BCMA), comprising CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of the VH-VL pair of SEQ ID NO: 170 and 217.
BCMA-binding VH and VL regions with variant substitution limits
An antibody comprising a VH region of SEQ ID NO: 170 or a variant with 20 or fewer amino acid substitutions, and a VL region of SEQ ID NO: 217 or a variant with 20 or fewer amino acid substitutions.
Specified heavy-chain CDR sequences for BCMA binding
An antibody that specifically binds to BCMA and includes specified heavy-chain CDR-H1, CDR-H2, and CDR-H3 sequences defined by particular SEQ ID NOs.
Specified light-chain CDR sequences
An antibody that includes a specified light-chain variable region containing CDR-L1, CDR-L2, and CDR-L3 with sequences SEQ ID NO: 146, 155, and 161, respectively.
Human BCMA binding characterized by association affinity at 25 C
The antibody binds to human BCMA at 25° C with an association characterized by an affinity (ka) in the range of about 4.57×10^5 to about 7.66×10^5 M−1.
Administration of the BCMA-binding antibody for treating BCMA-expressing cancer
Treating a BCMA-expressing cancer by administering to a subject in need thereof an effective amount of an antibody or a pharmaceutical composition.
Overall, the claim coverage focuses on an isolated IgG-class anti-BCMA antibody defined by six CDRs and a specified VH-VL pair (SEQ ID NO: 170 and 217), with further refinements to VH and VL variants, specific CDR sequences, binding association characteristics, and treatment of BCMA-expressing cancers.
Stated Advantages
Provides antibodies that specifically bind to B-cell maturation antigen (BCMA).
Enables BCMA binding to be characterized by an association affinity (ka) range at 25° C for human BCMA.
The antibodies are described as specifically binding BCMA with measurable binding and association kinetics characteristics.
The provided experimental content reports binding kinetics and affinity parameters (ka, kd, and KD) and thermo-stability temperatures for multiple BCMA antibody variants.
Documented Applications
Therapeutic methods for treating BCMA-expressing cancer by administering an effective amount of the antibody or a pharmaceutical composition.
Diagnostic methods.
Research applications.
Purifying and quantifying BCMA workflows.
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