EPHA2 antibodies
Inventors
Scholz, Alexander • Vad, Nikhil • WEISS, Michael Samuel • YE, Anne • ZHANG, Danhui • AYDIN, Iraz T. • BHATTI, Maryam M. • Carroll, Sean • Finn, Jessica • GAI, Shuning • Lippow, Shaun M. • Manning-Bog, Amy • MARGUET, Philippe • ATKINS, Ngan Nguyen
Assignees
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Publication Number
US-12162945-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Provided herein are EphA2 antibodies. These EphA2 antibodies bind preferentially to tumor tissue than normal tissue and bind to EphA2. Such antibodies are used in methods of inducing an immune response and methods of inhibiting tumor cell growth. Additionally provided are methods of producing such antibodies.
Core Innovation
The invention relates to antibodies that bind ephrin receptor A2 (EphA2) and are defined by specific variable heavy chain (VH) and variable light chain (VL) amino acid sequences, and by specific complementarity determining regions (HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3) corresponding to particular antibody designations. The antibodies bind an EphA2 epitope in the FN2 domain, with the FN2 domain epitope referenced as residues 437-534 and characterized by specific residue positions and regions.
The disclosed antibodies preferentially bind tumor tissue over normal tissue and selectively bind tumor-cell binding. Functional properties include reduced agonist activity and reduced agonistic signaling on the ephrinA1-EphA2 or ephrin A1-EphA2 signaling axis, as well as competition blocking. The document also provides an FN2 domain epitope sequence and EphA2 residues associated with that epitope.
The disclosure further includes antibody formats such as IgG subclasses and fragments, multivalent constructs, and bispecific antibodies in which EphA2 is paired with 4-1BB or CD3. It also describes Fc effector functions including ADCC, ADCP, and CDC, and immunoconjugates, all centered on specified EphA2-binding antibodies defined by exact sequence features.
Claims Coverage
Two independent claims are identified in the provided claim set. Across these claims, the coverage is grounded in sequence-defined EphA2-binding antibodies, with one claim constrained by specified VH/VL sequence pairs and the other constrained by specified CDR sets corresponding to a defined set of AB-designated antibodies.
Sequence-defined EphA2-binding antibody with specified VH and VL variable-region sequences
An antibody that binds ephrin receptor A2 (EphA2), comprising alternative VH and VL variable-region amino acid sequence assignments using SEQ ID NOs, with each alternative specifying a VH region sequence paired with a VL region sequence.
EphA2-binding antibody defined by specified CDR sets corresponding to AB-designated antibodies
An antibody that binds EphA2, comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of an antibody designated as one of the listed AB-designated antibodies.
Overall claim coverage is for EphA2-binding antibodies defined by exact sequence constraints: either by specifying VH and VL variable-region SEQ ID NO combinations, or by specifying CDRs corresponding to one of multiple AB-designated antibody members.
Stated Advantages
Preferential binding of tumor tissue over normal tissue.
Reduced agonist activity along the ephrin A1-EphA2 signaling axis.
Reduced agonistic signaling on the ephrinA1-EphA2 axis.
Tumor-cell binding with selectivity.
Competition blocking.
ADCC activity.
ADCP activity.
Immunotherapeutic mechanisms associated with Fc effector functions (ADCC, ADCP, CDC).
Therapeutic advantage described as limited agonism.
Useful for inducing immune responses.
Useful for treating cancers.
Useful for diagnosing tumors by antibody binding to tumors.
Documented Applications
Immunoconjugates that include EphA2-targeting antibodies.
Expression vectors and host cells that include recombinant nucleic acid encoding the antibodies.
Pharmaceutical compositions including the antibodies.
Patient selection by tumor EphA2 binding detection.
Methods of treating EphA2-overexpressing cancers.
Bispecific antibody formats, including EphA2 paired with 4-1BB and with CD3.
Immune response induction using the described EphA2-targeting antibody constructs.
Treating cancers using EphA2-targeting antibody constructs, including constructs combined with immune-modulating payloads and traps.
Diagnosing tumors by antibody binding, including tumor imaging using conjugated imaging agents as described in the document.
Selecting antibodies based on binding to EphA2 polypeptides.
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