Therapeutic agent targeted to receptor protein, test agent, antibody that binds to receptor protein, and screening method for molecularly targeted drugs
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Publication Number
US-12098205-B2
Publication Date
2024-09-24
Expiration Date
Abstract
From gene expression analysis with a long-term recurrence-free group and a recurrence metastasis group of stomach cancer, CHRNB2 and NPTXR were identified as drug discovery targets. Tumor growth was successfully inhibited by an antibody medicine or a nucleic acid medicine targeting CHRNB2 or NPTXR. Furthermore, a polyclonal antibody and a monoclonal antibody linking to CHRNB2 or NPTXR are provided. Since these receptor molecules are novel molecular targets, treatment of cases which the existing therapeutic drugs have no effect on is made possible.
Core Innovation
The patent addresses stomach cancer progression and identifies CHRNB2 and NPTXR as drug-discovery targets using gene expression profiling that compares long-term recurrence-free versus recurrence/metastasis patient groups. The disclosure states that loss or neutralization/inhibition of these receptor proteins reduces cancer cell proliferation, migration/invasion, apoptosis-related phenotypes, and tumorigenicity.
A specific invention aspect is directed to an isolated antibody that binds specifically to NPTXR and inhibits NPTXR function. The antibody is defined by three heavy chain complementarity determining regions and three light chain complementarity determining regions of an antibody produced by a hybridoma deposited with NITE Patent Microorganisms Depositary under Accession No. NITE BP-02856.
The disclosure also supports NPTXR and CHRNB2 as clinical biomarkers using quantitative expression analysis, including ROC/prognosis correlations and tissue microarray immunohistochemistry for normal and tumor expression. Targeted therapies and screening/test kits are positioned around CHRNB2/NPTXR expression or binding to exposed cell-surface regions, using the described antibodies and nucleic acid inhibitors directed to CHRNB2/NPTXR.
Claims Coverage
The independent claim defines one inventive feature: an isolated anti-NPTXR antibody that inhibits NPTXR function and is defined by six complementarity determining regions from an NPMD-deposited hybridoma with Accession No. NITE BP-02856. Dependent claims further define the antibody by sequence or variable-region constraints and extend coverage to pharmaceutical, kit, and molecular target therapeutic drug formats.
Isolated anti-nptxr inhibiting antibody defined by NPMD hybridoma CDRs
An isolated antibody that binds specifically to NPTXR and inhibits NPTXR function, comprising three heavy chain complementarity determining regions and three light chain complementarity determining regions of an antibody produced by a hybridoma deposited with NITE Patent Microorganisms Depositary under Accession No. NITE BP-02856.
Sequence-defined anti-NPTXR binding antibody
An anti-NPTXR antibody recognizing one of the specified amino acid sequences CESGLPRGLQGAGPRRDT, KERVALSHSSRRQRQEVE, or SEQ ID NO: 12 (GLPRGLQGAGPRRDT).
Variable-region defined anti-NPTXR antibody
An anti-NPTXR antibody including specific heavy-chain and light-chain variable regions from an antibody produced by a hybridoma deposited with NITE Patent Microorganisms Depositary under Accession No. NITE BP-02856.
Pharmaceutical composition including the anti-NPTXR antibody
A pharmaceutical composition that includes the anti-NPTXR antibody, optionally combined with a pharmaceutically acceptable carrier or excipient.
Kit including the anti-NPTXR antibody
A kit that includes the anti-NPTXR antibody.
Molecular target therapeutic drug including the anti-NPTXR antibody
A molecular target therapeutic drug formulated to include the anti-NPTXR antibody.
Overall, the claim set centers on an isolated NPTXR-inhibiting antibody specified by CDR sets from an NPMD-deposited hybridoma, with dependent coverage further constrained by amino acid sequence and variable-region definitions and broadened into pharmaceutical, kit, and molecular target therapeutic drug formats.
Stated Advantages
Reduces cancer cell proliferation, migration/invasion, and apoptosis-related phenotypes.
Reduces tumorigenicity in mouse xenograft/dissemination models.
Provides clinical biomarker use for CHRNB2 and NPTXR through quantitative expression analysis and ROC/prognosis correlations.
Supports targeted therapies and screening/test kits based on CHRNB2/NPTXR expression or binding to exposed cell-surface regions.
Documented Applications
Biomarker-based clinical assessment and prognosis support using quantitative expression analysis and ROC/prognosis correlations for CHRNB2 and NPTXR.
Tissue microarray immunohistochemistry for normal and tumor expression of CHRNB2 and NPTXR as part of the described biomarker approach.
Targeted therapies based on CHRNB2/NPTXR expression or binding to exposed cell-surface regions.
Screening/test kits based on CHRNB2/NPTXR expression or binding to exposed cell-surface regions.
Therapeutic use of anti-NPTXR antibody as a molecular target therapeutic drug formulation.
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