Glucose transporter 4 antibodies, methods of making the same, and uses thereof
Inventors
TUCKER, David F. • Mattia, Kimberly-Anne • FISHER, Christine R. • Doranz, Benjamin J. • RUCKER, Joseph B.
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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-11834497-B2
Publication Date
2023-12-05
Expiration Date
Abstract
Antibodies and compositions against GLUT4 and uses thereof are provided herein.
Core Innovation
The invention relates to an antibody, or an antigen binding fragment thereof, that binds to a GLUT4 protein. The antibody comprises a light chain variable (V_L) region and a heavy chain variable (V_H) region, each defined by specified CDR1, CDR2, and CDR3 amino acid sequences selected from multiple SEQ ID-defined options.
The invention also relates to recombinant antibody formats including an scFv and linked variable regions, and to the generation of GLUT4-targeting antibodies using GLUT4-expressing virus-like particles (VLPs) and chicken immunization and/or phage display. The disclosed antibodies are identified as conformationally sensitive GLUT4 monoclonal antibodies, with examples including AB102, AB105, AB108, and AB111, and with binding behavior described as extracellular versus intracellular binding and state-dependent binding with respect to inward-open versus outward-open GLUT4.
The disclosed antibodies are further characterized as having high specificity across GLUT family members and strong apparent affinities for native GLUT4. Conformational sensitivity is linked to GLUT4 conformational lock perturbations using GLUT4 conformational lock mutants and GLUT4 mutant antigens locked in specific conformations.
Claims Coverage
The independent claim covers a GLUT4-binding antibody or antigen binding fragment defined by specific LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 amino acid sequences matching one of multiple SEQ ID sets. The claim centers on six CDR sequence assignments across alternative SEQ ID-defined options.
Glut4-binding antibody with defined light- and heavy-chain CDR sequences
An antibody, or antigen binding fragment thereof, that binds to a GLUT4 protein, wherein the antibody comprises a light chain variable (V_L) region with LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NOs: 42, 18, 24, 60, or 78; 43, 19, 25, 61, or 79; and 44, 20, 26, 62, or 80, and a heavy chain variable (V_H) region with HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NOs: 45, 21, 27, 63, or 81; 46, 22, 28, 64, or 82; and 47, 23, 29, 65, or 83.
Overall, the claim coverage centers on a GLUT4-binding antibody or antigen binding fragment whose binding specificity is defined by fixed, SEQ ID-defined CDR1, CDR2, and CDR3 amino acid sequences in both the light and heavy chain variable regions, selected from multiple coordinated alternative sets.
Stated Advantages
High specificity across GLUT family members.
Strong apparent affinities for native GLUT4, including pM range with AB105 <1 pM.
State-dependent binding with inward-open versus outward-open GLUT4.
Modulation or inhibition of GLUT4 internalization/function is described.
Inhibition of 2-deoxyglucose transport is described for the GLUT4 monoclonal antibodies.
The antibodies are described as having characterization support including affinity and epitope/residue mapping.
Documented Applications
Modulating GLUT4 internalization by contacting a GLUT4-expressing cell with the antibody or antigen-binding fragment, or a pharmaceutical composition containing the same.
Inhibiting GLUT4 function (glucose transport) is described as a downstream use case of the disclosed antibodies.
Pharmaceutical compositions containing the antibody are described.
Treating GLUT4-mediated disorders is described.
Nucleic acids encoding the antibody are described as part of the covered embodiments.
Diagnostic/monitoring kits are described as downstream use cases.
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