Compositions and methods related to GPRC5D binding agents and variants thereof
Inventors
Barnes, Trevor • Roth, Hayley • RUCKER, Joseph B. • Chambers, Ross • Doranz, Benjamin J.
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Assignees
MemberIntegral MolecularIntegral MolecularIntegral Molecular is a biotechnology company specializing in technologies and services for antibody discovery, engineering, and specificity testing, with a focus on membrane proteins, viruses, and related biotherapeutics. The company’s platforms support antibody development, comprehensive protein-level specificity assessment, and virology research. Integral Molecular collaborates with industry partners and regulators, and its tools have contributed to regulatory innovations, hundreds of published studies, and the advancement of new therapeutics across oncology, infectious disease, and autoimmune disorders.
Integral Molecular is a biotechnology company specializing in technologies and services for antibody discovery, engineering, and specificity testing, with a focus on membrane proteins, viruses, and related biotherapeutics. The company’s platforms support antibody development, comprehensive protein-level specificity assessment, and virology research. Integral Molecular collaborates with industry partners and regulators, and its tools have contributed to regulatory innovations, hundreds of published studies, and the advancement of new therapeutics across oncology, infectious disease, and autoimmune disorders.
Publication Number
US-12545726-B1
Publication Date
2026-02-10
Expiration Date
Abstract
The present disclosure describes compositions and methods related to GPRC5D binding agents.
Core Innovation
The invention provides antibodies that bind to GPRC5D. The antibodies include a heavy chain variable region and a light chain variable region, each defined by specific CDR amino acid sequences. The heavy chain CDRs comprise HCDR1 as SYGMG (SEQ ID NO: 4) or a variant thereof, HCDR2 as AGIDNTGRYTGYGSAVKG (SEQ ID NO: 5) or a variant thereof, and HCDR3 as PTCSGRDDCWYSAAGIDA (SEQ ID NO: 6) or a variant thereof.
The light chain CDRs comprise LCDR1 as SGGSYRYG (SEQ ID NO: 1) or a variant thereof, LCDR2 as GTNKRPS (SEQ ID NO: 2) or a variant thereof, and LCDR3 as GSRDSSYFSL (SEQ ID NO: 3) or a variant thereof. Each CDR variant is limited to substitutions at defined positions within the CDRs, with allowed amino acid sets specified for each position.
The disclosure identifies the need for antibodies that bind to GPRC5D with improved binding reactivity compared with a wild-type GPRC5D antibody. Antibody engineering is guided by CDR scanning and paratope mapping, supported by high-throughput mutagenesis and ELISA readouts, and reports binding-reactivity increases versus the wild-type antibody.
Claims Coverage
Independent claim clm-00001 covers a GPRC5D-binding antibody with specified heavy- and light-chain CDR sequences (SEQ ID NOs 1–6) and limited permissible substitution variants at defined CDR positions. Dependent claims refine antibody format, variable region framework architecture, constant-region content, and additional sequence identity constraints.
GPRC5D-binding antibody with specified CDR sequences and constrained substitution variants
An antibody that binds to GPRC5D comprising a heavy chain variable region with HCDR1 SYGMG (SEQ ID NO: 4) (or variant), HCDR2 AGIDNTGRYTGYGSAVKG (SEQ ID NO: 5) (or variant), and HCDR3 PTCSGRDDCWYSAAGIDA (SEQ ID NO: 6) (or variant), and a light chain variable region with LCDR1 SGGSYRYG (SEQ ID NO: 1) (or variant), LCDR2 GTNKRPS (SEQ ID NO: 2) (or variant), and LCDR3 GSRDSSYFSL (SEQ ID NO: 3) (or variant), wherein each variant is limited to substitutions at defined CDR positions using specified amino-acid sets.
Antibody format as scFv, Fv, Fab, Fab’2, or F(ab’)2
The antibody of claim 1 that is selected from scFv, Fv, Fab, Fab’2, or F(ab’)2.
Framework/C regional architecture defined by a FW/CDR framework order
The antibody of claim 1 wherein variable region framework (FW) sequences are positioned between the CDRs in a specified order, with heavy-chain FW sequences in the heavy chain variable region and light-chain FW sequences in the light chain variable region using a FW1–CDR1–FW2–CDR2–FW3–CDR3–FW4 framework arrangement.
Human heavy chain and light chain constant regions
The antibody of claim 1 further includes human heavy chain constant regions and human light chain constant regions.
Constant region subclass selection among IgG1, IgG2, IgG3, and IgG4
The antibody of claim 1 wherein the constant regions are selected from IgG1, IgG2, IgG3, and IgG4.
Sequence-identity constrained embodiments using additional heavy and light variable sequences
The antibody wherein the heavy chain variable region matches SEQ ID NO: 7 (or has at least 95% identity) and the light chain variable region matches SEQ ID NO: 8 (or has at least 95% identity).
Overall, the claim set is centered on GPRC5D-binding antibodies defined by specific HCDR and LCDR sequences (SEQ ID NOs 1–6) with constrained substitution variants at defined positions, with further narrowing by antibody format, framework architecture, constant-region human content and IgG subclass selection, and embodiments meeting additional sequence-identity constraints (SEQ ID NOs 7 and 8).
Stated Advantages
Increased binding reactivity versus a wild-type GPRC5D antibody, including reported increases of at least 20%, at least 50%, and at least 80%.
Documented Applications
Targeting or treating diseases including autoimmune diseases and cancers such as multiple myeloma.
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