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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-10030076-B2
Publication Date
2018-07-24
Expiration Date
Abstract
The present disclosure is directed to antibodies binding to ELTDI. Plexin-B2, Spondin-1, fibulin-1, LINGO I or SLIT3 and methods of using such antibodies to treat and/or diagnose gliomas. Thus, in accordance with the present disclosure, there is provided a method of inhibiting a glioma cell comprising contacting said glioma cell with a first antibody or antibody fragment that binds immunologically to ELTDI, Plexin-B2, Spondin-1 or SLIT3. The method may further comprise contacting said glioma cell with a second anti-cancer agent or treatment.
Core Innovation
The disclosure identifies and validates glioma-associated surface proteins including ELTD1, Plexin-B2, Spondin-1 (SPON1), SLIT3, Fibulin-1 (FBLN1) and LINGO1, and claims methods of inhibiting or treating glioma by contacting glioma cells or subjects with antibodies or antibody fragments that bind these targets. The specification describes antibody formats (scFv, Fab, IgG; humanized, murine, chimeric), conjugates and payloads, linker types, carrier conjugates, labels, imaging agents, and combination therapies.
Preclinical in vivo data in the GL261 mouse glioma model report that anti-ELTD1, anti-Plexin-B2, anti-Spondin-1 and anti-SLIT3 antibodies reduce tumor volume, decrease mitotic index and microvessel density, alter perfusion and angiography metrics, and increase animal survival versus controls, supporting therapeutic and diagnostic claim scope. The disclosure further describes dosing and routes of administration [procedural detail omitted for safety] and diagnostic methods including immunohistochemistry, MRI, MRA and perfusion imaging.
Claims Coverage
Overview: Two independent claims. Two inventive features directed to antibody-based inhibition or treatment of glioma by binding ELTD1, Spondin-1 or SLIT3.
Antibody binding to ELTD1, Spondin-1 or SLIT3
A method of inhibiting a glioma cell comprising contacting said glioma cell with a first antibody or antibody fragment that binds immunologically to ELTD1, Spondin-1 or SLIT3.
Administration of antibody binding to ELTD1, Spondin-1 or SLIT3 to a subject
A method of treating glioma in a subject comprising administering to said subject a first antibody or antibody fragment that binds immunologically to ELTD1, Spondin-1 or SLIT3.
The independent claims are directed to antibody-based methods that target ELTD1, Spondin-1 or SLIT3 for inhibition of glioma cells and for treatment of glioma in subjects.
Stated Advantages
Reduction in tumor volume observed with anti-ELTD1, anti-Plexin-B2, anti-Spondin-1 and anti-SLIT3 antibodies in the GL261 mouse glioma model.
Decrease in mitotic index and decrease in microvessel density following antibody treatment in the GL261 mouse glioma model.
Alteration of perfusion and angiography metrics after antibody treatment in the GL261 mouse glioma model.
Increase in animal survival versus controls in the GL261 mouse glioma model following antibody treatment.
Support for both therapeutic and diagnostic claim scope based on the reported preclinical results.
Documented Applications
Inhibiting glioma cells by contacting the cells with an antibody or antibody fragment that binds ELTD1, Spondin-1 or SLIT3.
Treating glioma in a subject by administering an antibody or antibody fragment that binds ELTD1, Spondin-1 or SLIT3.
Use of antibody conjugates and payloads (toxins, radioisotopes, cytokines, enzymes) and linker types (photolabile, enzymatically cleavable) for targeted delivery.
Use of carrier conjugates (liposomes, nanoparticles), labels and imaging agents (fluorophores, MRI contrast agents, radioisotopes) for diagnostic imaging and detection.
Combination therapy with other anti-cancer agents, exemplified by anti-VEGF, anti-EGFR and anti-c-Met.
Diagnostic methods including immunohistochemistry (IHC), MRI, MRA and perfusion imaging.
Administration routes and dosing regimens [procedural detail omitted for safety].
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