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Assignees
Member
Oklahoma Medical Research FoundationFounded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Founded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Publication Number
US-12415851-B2
Publication Date
2025-09-16
Expiration Date
Abstract
The present disclosure is directed to novel monoclonal antibodies that bind to ELTD 1 and methods for use thereof, including, detection and treatment of cancer, multiple sclerosis, retinopathy, or promoting tissue regeneration.
Core Innovation
The invention provides anti-ELTD1 monoclonal antibodies and anti-ELTD1 single-chain variable fragments, including scFv and bivalent scFv-Fc fusions, that target the 430-aa external ELTD1 region and are defined by specified variable-region sequences and complementarity determining region sets. Antibodies or fragments bind specifically to ELTD1 and are formulated for therapeutic use. The disclosure further describes albumin–Gd–DTPA–biotin linked antibodies used as molecular-targeted MRI probes.
In G55 and GL261 xenograft models, treatment reduces glioma tumor volume, increases survival, normalizes tumor perfusion (rCBF), lowers microvessel density, and decreases Notch1 and VEGFR2 in tumors. RNA-seq shows downregulation of pro-tumor and poor-prognosis genes including ADA, BMP2, SCN5A, TRPM8, ALPL and L1CAM, and downregulation of nestin-related pathways. Examples report tumor-specific targeting and reduced hemorrhage relative to anti-VEGF.
Albumin–biotin–Gd–DTPA probes conjugated to anti-ELTD1 mAb or scFv cross the blood-brain barrier and enable molecular-targeted MRI detection. Probes and antibodies localize to bulk and diffuse tumor regions, with scFv showing delayed but broader localization. Diagnostic and therapeutic uses are reported in retinopathy, tissue-regeneration models, and an EAE mouse multiple sclerosis model.
Claims Coverage
This coverage identifies four independent claims covering a pharmaceutical formulation, therapeutic methods for glioma/glioblastoma, a monoclonal antibody composition defined by paired variable-region sequences, and an identify-and-treat method.
Pharmaceutical formulation comprising anti-ELTD1 monoclonal antibody with specified CDRs
A pharmaceutical formulation comprising an anti-EGF, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) monoclonal antibody, or one or more anti-ELTD1 monoclonal antibody fragments thereof, wherein the antibody or one or more antibody fragments thereof have light chain variable region complementarity determining regions (CDR) CDR1, CDR2, and CDR3 of SEQ ID NOS: 25, 26 and 27; 31, 32 and 33; 37, 38 and 39; 43, 44 and 45; 49, 50 and 51; 55, 56 and 57; 61, 62 and 63; 67, 68 and 69; 73, 74 and 75; 79, 80 and 81; 85, 86 and 87; 91, 92 and 93; 109, 110 and 111; 115, 116 and 117; 121, 122 and 123; or 127, 128 and 129, respectively; and the antibody has heavy chain variable regions CDR1, CDR2, and CDR3 of SEQ ID NOS: 28, 29 and 30; 88, 35 and 36; 40, 41 and 42; 46, 47 and 48; 58, 59 and 60; 64, 65 and 66; 70, 71 and 72; 76, 77 and 78; 82, 83 and 84; 88, 89 and 90; 94, 95 and 96; 100, 101 and 102; 106, 107 and 108; 112, 113 and 114; or 118, 119 and 120, respectively.
Method of treating glioma and glioblastoma using anti-ELTD1 antibody with specified CDRs
A method of treating a subject with cancer comprising administering to the subject with cancer a therapeutically effective amount of an anti-ELTD1 monoclonal antibody or antibody fragment, wherein the cancer is glioma, glioblastoma, and/or glioblastoma multiforme, and wherein the monoclonal antibody or antibody fragment comprises light chain variable regions CDR1, CDR2, and CDR3 of SEQ ID NOS: 25, 26 and 27; 31, 32 and 33; 37, 38 and 39; 43, 44 and 45; 49, 50 and 51; 55, 56 and 57; 61, 62 and 63; 67, 68 and 69; 73, 74 and 75; 79, 80 and 81; 85, 86 and 87; 91, 92 and 93; 109, 110 and 111; 115, 116 and 117; 121, 122 and 123; or 127, 128 and 129, respectively; and the antibody has heavy chain variable regions CDR1, CDR2, and CDR3 of SEQ ID NOS: 28, 29 and 30; 88, 35 and 36; 40, 41 and 42; 46, 47 and 48; 58, 59 and 60; 64, 65 and 66; 70, 71 and 72; 76, 77 and 78; 82, 83 and 84; 88, 89 and 90; 94, 95 and 96; 100, 101 and 102; 106, 107 and 108; 112, 113 and 114; or 118, 119 and 120, respectively.
Monoclonal antibody or fragment that binds ELTD1 comprising specified variable region sequences
A monoclonal antibody or fragment thereof that binds specifically to ELTD1 comprising a light chain variable region and a heavy chain variable region with amino acid sequences of SEQ ID NOS: 2 and 4, 6 and 8, 10 and 12, 14 and 16, 18 and 20, or 22 and 24, respectively.
Method of identifying and treating cancer using anti-ELTD1 antibody with specified CDRs
A method of treating a cancer with an anti-EGF, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) antibody or fragment thereof comprising identifying a subject with cancer and administering to the subject with cancer a therapeutically effective amount of the anti-ELTD1 antibody or fragment thereof sufficient to reduce the symptoms from or treat the cancer, wherein the cancer is glioma, glioblastoma, and/or glioblastoma multiforme, and wherein the antibody or fragment thereof has light chain variable regions CDR1, CDR2, and CDR3 of SEQ ID NOS: 25, 26 and 27; 31, 32 and 33; 37, 38 and 39; 43, 44 and 45; 49, 50 and 51; 55, 56 and 57; 61, 62 and 63; 67, 68 and 69; 73, 74 and 75; 79, 80 and 81; 85, 86 and 87; 91, 92 and 93; 109, 110 and 111; 115, 116 and 117; 121, 122 and 123; or 127, 128 and 129, respectively; and the monoclonal antibody has heavy chain variable regions CDR1, CDR2, and CDR3 of SEQ ID NOS: 28, 29 and 30; 88, 35 and 36; 40, 41 and 42; 46, 47 and 48; 58, 59 and 60; 64, 65 and 66; 70, 71 and 72; 76, 77 and 78; 82, 83 and 84; 88, 89 and 90; 94, 95 and 96; 100, 101 and 102; 106, 107 and 108; 112, 113 and 114; or 118, 119 and 120, respectively.
The independent claims cover anti-ELTD1 monoclonal antibodies and fragments defined by enumerated light- and heavy-chain CDR sequences, methods of treating glioma/glioblastoma by administering such antibodies or fragments, a monoclonal antibody composition defined by paired variable-region sequences, and an identify-and-treat method specifying administration to reduce symptoms or treat cancer.
Stated Advantages
Reduce glioma tumor volume.
Increase survival in G55 and GL261 xenograft models.
Normalize tumor perfusion (rCBF) and reduce microvessel density (MVD).
Decrease Notch1 and VEGFR2 in tumors.
Downregulate pro-tumor and poor-prognosis genes (e.g., ADA, BMP2, SCN5A, TRPM8, ALPL, L1CAM) and nestin-related pathways.
Do not induce hemorrhage as observed with bevacizumab (Avastin).
Cross the blood-brain barrier and enable molecular-targeted MRI detection when conjugated to albumin–biotin–Gd–DTPA probes.
Localize to bulk and diffuse tumor regions, with scFv showing delayed but broader localization.
Tumor-specific targeting and superior binding compared with polyclonal antibody or IgG control for molecular probes.
Support diagnostic and therapeutic uses in retinopathy, tissue-regeneration models, and an EAE (mouse MS) model.
Documented Applications
Treatment of glioma, glioblastoma, and glioblastoma multiforme using anti-ELTD1 monoclonal antibodies or antibody fragments.
Pharmaceutical formulations comprising anti-ELTD1 monoclonal antibodies or antibody fragments defined by specified CDR sequences.
Molecular-targeted MRI detection using albumin–biotin–Gd–DTPA probes conjugated to anti-ELTD1 mAb or scFv that cross the blood-brain barrier and localize to tumor regions.
Diagnostic and therapeutic uses in retinopathy.
Diagnostic and therapeutic uses in tissue regeneration.
Therapeutic use in an EAE mouse model of multiple sclerosis.
mtMRI detection of elevated ELTD1 in an EAE (mouse MS) model.
Mentioned disease indications including metastatic colorectal cancer, non-squamous non-small cell lung cancer, renal cell carcinoma, and ovarian/cervical cancers.
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