Antibodies and methods for the diagnosis, prevention, and treatment of Epstein Barr virus infection
Inventors
Kanekiyo, Masaru • Joyce, Michael Gordon • Bu, Wei • Cohen, Jeffrey I. • Tsybovsky, Yaroslav
Assignees
Henry M Jackson Foundation for Advancedment of Military Medicine Inc • US Department of Health and Human Services
Publication Number
US-12084489-B2
Publication Date
2024-09-10
Expiration Date
2039-05-02
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Anti-EBV gH antibodies, anti-EBV gL antibodies, anti-EBV gH/gL antibodies, and compositions of matter useful for the detection, diagnosis, prevention, and treatment of Epstein Barr Virus infection in humans, and methods of using those compositions of matter for the same.
Core Innovation
The invention relates to antibodies that specifically recognize Epstein Barr virus (EBV) glycoprotein H (gH), glycoprotein L (gL), or the gH/gL complex. These antibodies include monoclonal antibodies (mAbs) isolated from humans naturally infected with EBV, which have greater EBV neutralizing activity on B cells and at least comparable neutralizing activity on epithelial cells relative to previously known murine antibodies. The compositions of these antibodies are useful for the detection, diagnosis, prevention, and treatment of EBV infections and EBV-associated diseases in humans.
Epstein-Barr virus infection is widespread and can cause infectious mononucleosis, chronic active EBV infection, and is associated with various malignancies such as Hodgkin disease, lymphomas, nasopharyngeal carcinoma, and gastric carcinoma. Immunocompromised individuals, such as transplant recipients who are EBV-seronegative, are at increased risk for EBV-associated posttransplant lymphoproliferative disorder (PTLD). Since EBV infects both B cells and epithelial cells using distinct glycoprotein complexes for entry and spread, the invention addresses the need for antibodies targeting gH, gL, or the gH/gL complex that can neutralize infection in both cell types and serve diagnostic and therapeutic purposes.
Claims Coverage
The claims detailed in the patent encompass one independent claim describing a monoclonal antibody with specific features, followed by dependent claims that elaborate on antibody sequences, structures, methods of use, compositions, and applications.
Monoclonal antibody comprising specific heavy and light chain CDR sequences binding to EBV gH, gL, or gH/gL complex
A monoclonal antibody comprising heavy chain complementary determining region (CDR) 1, 2, and 3 sequences selected from a specific group of sequences (SEQ ID NOs 1, 11, 21, etc.) and light chain CDR 1, 2, and 3 sequences from another defined group (SEQ ID NOs 6, 16, 26, etc.), wherein the antibody binds to an Epstein Barr Virus gH protein, gL protein, or a gH/gL complex.
Monoclonal antibody with defined CDR segments corresponding to detailed sequence groups
An antibody comprising heavy chain CDR1, CDR2, and CDR3 sequences and light chain CDR1, CDR2, and CDR3 sequences selected from 20 specific sets of sequences enumerated by SEQ ID NOs, providing defined antigen-binding properties.
Monoclonal antibody comprising full variable heavy and light chain sequences from specific pairs
An antibody comprising paired VH and VL sequences from a specific set of 20 defined variable heavy and light chain sequences, including SEQ ID NOs for full variable sequences, to confer binding specificity against EBV gH, gL, or gH/gL complex.
Variants of monoclonal antibody including fragments, chimeric forms, and bispecific antibodies
The antibody can be in fragment form, be a chimeric antibody, or a bispecific antibody that binds multiple epitopes or proteins.
Conjugated monoclonal antibody with cytotoxic, growth inhibitory, or detectable labels or bound to solid supports
The antibody may be conjugated to a growth inhibitory agent, a cytotoxic agent, a label such as a radioisotope or fluorescent label, or immobilized on solid supports for diagnostic or therapeutic applications.
Production of monoclonal antibodies in various expression systems
Methods include producing the monoclonal antibody in mammalian cells, insect cells, yeast cells, or bacterial cells.
Monoclonal antibody inducing cell death upon binding to target cells
The antibody can induce death of cells expressing EBV gH, gL, or gH/gL complex, providing therapeutic cytotoxic function.
Compositions comprising monoclonal antibody with carriers
Pharmaceutical or other compositions containing the monoclonal antibody with suitable carriers including pharmaceutically acceptable carriers.
Materials for packaging and labeling for therapeutic, prophylactic, or diagnostic use
Articles of manufacture including containers holding antibody compositions with labeled instructions for use in prevention, treatment, or diagnosis of EBV infection.
Methods of inhibiting growth of cells expressing EBV gH, gL, or gH/gL by antibody binding
Method for inhibiting cell growth of cells expressing EBV gH, gL, or gH/gL complex by contacting with the monoclonal antibody that binds these proteins, causing growth inhibition.
Treatment methods for EBV infection using monoclonal antibodies
Administering an effective amount of the monoclonal antibody to individuals infected with EBV to therapeutically inhibit the virus or EBV-associated diseases.
Diagnostic methods detecting EBV proteins using antibodies
Methods of detecting presence of EBV gH, gL, or gH/gL proteins in samples by exposing the sample to the monoclonal antibody and detecting its binding.
Methods of diagnosing EBV infection in individuals using antibody binding
Detecting EBV infection by assaying tissue or cell samples with the monoclonal antibody and detecting complex formation indicative of infection.
Methods of combined diagnosis and treatment based on expression levels of EBV gH or gL
Determining elevated levels of EBV gH or gL gene expression in test samples compared to controls to indicate EBV infection and administering the monoclonal antibody to inhibit the infection.
Methods of inhibiting EBV infection in subjects by antibody administration
Providing prophylactic or therapeutic antibody treatment to subjects to inhibit EBV infection by administering an effective amount of the monoclonal antibody.
The claims cover specifically defined monoclonal antibodies targeting EBV gH, gL, or their complex with detailed sequence definitions, antibody structural variants and conjugates, methods for producing antibodies, compositions containing them, diagnostic and therapeutic methods using the antibodies, and articles of manufacture including kits and diagnostic devices.
Stated Advantages
Monoclonal antibodies described in the disclosure have greater EBV neutralizing activity on B cells and at least comparable neutralizing activity on epithelial cells compared to previously known murine antibodies.
The antibodies serve as high value reagents usable in immunoassay development and as immunodiagnostic tools for clinical confirmation of EBV infection.
Antibodies can inhibit infection and spread of EBV in both B cells and epithelial cells, thereby potentially preventing initiation and propagation of infection.
Antibody-mediated blocking of membrane fusion critical to EBV infection may prevent both cell-free and cell-to-cell viral spread.
Documented Applications
Use of anti-EBV gH, gL, or gH/gL antibodies in detection and diagnosis of active EBV infection in individuals.
Use of these antibodies for prevention of EBV infection in individuals, including EBV-naïve subjects to prevent primary infection.
Therapeutic treatment of individuals with an EBV infection or EBV-associated diseases using the antibodies.
Treatment or prevention of EBV infection-related disorders, including infectious mononucleosis, various lymphomas, nasopharyngeal carcinoma, gastric cancer, autoimmune diseases, and posttransplant lymphoproliferative disorder (PTLD).
Use in inhibiting proliferation or inducing death of EBV-infected or gH/gL-expressing cells in vitro and in vivo.
Diagnostic assays employing the antibodies for detecting EBV gH, gL, or gH/gL proteins in biological samples or tissue biopsies.
Use in antibody-drug conjugates, immunoliposomes, or other formulations to enhance delivery and efficacy against EBV-infected cells.
Kits and assay devices including labeled antibodies useful for point-of-care diagnostics such as lateral flow assay devices for EBV infection detection.
Interested in licensing this patent?