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-11773169-B2
Publication Date
2023-10-03
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 identifies CHRNB2 and NPTXR as stomach cancer progression targets by transcriptome analysis comparing long-term recurrence-free patients versus patients with recurrence metastasis. High expression of CHRNB2 and NPTXR correlates with recurrence and metastasis, linking these genes to cancer progression.
The document reports functional results showing that loss of CHRNB2 or NPTXR reduces proliferation, migration, invasion, adhesion, and tumorigenicity while increasing apoptosis. It also reports that NPTXR functional inhibition supports reduced cancer progression in cellular settings.
In vivo, the patent describes mouse models of subcutaneous tumor growth and peritoneal dissemination in which targeting CHRNB2 and/or NPTXR reduces tumor growth. The patent also describes antibody therapies directed to CHRNB2 and NPTXR, including antibodies against specific NPTXR epitopes/peptides and nucleic acid inhibition approaches, and links these interventions to reduced cancer progression outcomes.
Claims Coverage
The provided independent claim is clm-00001, and it recites administering a therapeutically effective anti-NPTXR antibody with specified complementarity determining regions to treat cancer in a patient. The claim family further specifies tumor NPTXR expression, the hybridoma source by a specific NPMD accession, an NPTXR expression testing workflow, recognized amino-acid sequences, and antibody variable-region composition from the deposited hybridoma.
Anti-NPTXR antibody with specified HCDR and LCDR regions for treating NPTXR-expressing cancer
Administering to the patient a therapeutically effective amount of an anti-neuronal pentraxin receptor (NPTXR) antibody having three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the anti-NPTXR antibody binds specifically to NPTXR and inhibits NPTXR function, and wherein the cancer expresses NPTXR and is selected from stomach cancer, colorectal cancer, breast cancer, pancreatic cancer, and esophageal cancer.
High NPTXR-expression tumor selection
Treating cancer in a patient where the tumor exhibits high NPTXR expression.
NPTXR antibody from a specific deposited hybridoma
Using an anti-NPTXR antibody produced by a hybridoma deposited with NITE Patent Microorganisms Depositary (NPMD) and assigned with Accession No. NITE BP-02856.
NPTXR expression testing using a test kit
Including testing NPTXR expression using a test kit that contains an antibody for recognizing NPTXR or a primer for quantifying NPTXR mRNA, together with a reagent for measurement.
Anti-NPTXR antibody recognizing specified NPTXR amino-acid sequences
Using an anti-NPTXR antibody that recognizes one of the specified amino acid sequences selected from SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12.
Antibody composition defined by HCVR and LCVR from the deposited hybridoma
Defining that the anti-NPTXR antibody includes a heavy chain variable region (HCVR) and a light chain variable region (LCVR) from an antibody produced by the hybridoma deposited with NPMD under Accession No. NITE BP-02856.
Overall, the claim set focuses on therapeutic administration of an anti-NPTXR antibody with specified complementarity determining regions that binds specifically to NPTXR and inhibits its function, together with claim-dependent refinements that define tumor NPTXR expression context, antibody source via a specific deposited hybridoma accession, an associated NPTXR expression testing approach, recognition of specified NPTXR amino-acid sequences, and heavy/light variable-region composition derived from the deposited hybridoma.
Stated Advantages
Reduced tumor growth in in vivo models (subcutaneous tumor model and peritoneal dissemination model) when targeting CHRNB2 and/or NPTXR.
Reduced proliferation, migration, invasion, adhesion, and tumorigenicity when CHRNB2 or NPTXR is lost, with increased apoptosis reported for both targets.
Inhibition of NPTXR function by an anti-NPTXR antibody that binds specifically to NPTXR.
Use of CHRNB2/NPTXR expression as companion diagnostics and prognosis markers.
Documented Applications
A method of treating cancer in a patient by administering an anti-NPTXR antibody; the cancer is selected from stomach cancer, colorectal cancer, breast cancer, pancreatic cancer, and esophageal cancer.
Companion diagnostics and prognosis forecast using CHRNB2/NPTXR expression with immunohistochemistry/tissue microarrays and clinical expression analysis.
Therapeutic antibody applications directed to specific CHRNB2 and NPTXR epitopes/peptides, including an NPTXR epitope described as GLPRGLQGAGPRRDT (SEQ ID NO:12).
Therapeutic nucleic-acid inhibition described as siRNA targeting CHRNB2/NPTXR with reduced mRNA and reduced proliferation [procedural detail omitted for safety].
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