Monoclonal antibody for spike protein of middle east respiratory syndrome coronavirus, and use thereof
Inventors
Lee, Hansaem • Choi, Janghoon • Kim, Sungsoon • Wang, Lingshu • Graham, Barney • Mascola, John R
Assignees
Korea Centers for Disease Control and Prevention • US Department of Health and Human Services
Publication Number
US-12077572-B2
Publication Date
2024-09-03
Expiration Date
2038-08-23
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Abstract
The present invention relates to monoclonal antibodies for a spike protein of the Middle East respiratory syndrome coronavirus (MERS-CoV), and a use thereof. Particularly, monoclonal antibodies 77-A5, 77-A6, 90-A3, 90-A9, 90-B2, 90-B7, 90-C4, 90-E5, 90-E6, 90-F1 and 90-F2 according to the present invention have excellent attachment force with respect to a full-length spike protein of MERS-CoV and the S1 domain of the protein, and, of the monoclonal antibodies, the monoclonal antibodies 90-F1, 90-E5, 90-E6, 90-F2, 77-A5 and 77-A6 have excellent attachment force with respect to an RBD antigen of MERS-CoV. Also, the antibodies 77-A5, 77-A6, 90-E5, 90-E6, 90-F1 and 90-F2 exhibit neutralizing capacity with respect to a MERS pseudovirus and MERS-CoV, and the antibodies 90-B2 and 90-B7 exhibit neutralizing capacity only with respect to MERS-CoV. Further, the monoclonal antibodies have a particular monomeric form, and have excellent stability and thus may be useful for treating or diagnosing MERS.
Core Innovation
The invention relates to monoclonal antibodies specifically binding to the spike protein of Middle East respiratory syndrome coronavirus (MERS-CoV), including antibodies 77-A5, 77-A6, 90-A3, 90-A9, 90-B2, 90-B7, 90-C4, 90-E5, 90-E6, 90-F1, and 90-F2 that demonstrate excellent adhesion to the full-length spike protein and its S1 domain. Some antibodies also exhibit strong attachment to the receptor binding domain (RBD) antigen. Certain antibodies among these show neutralizing capacity against MERS pseudovirus and MERS-CoV, and others neutralize only MERS-CoV. Furthermore, these monoclonal antibodies have a particular monomeric form and excellent stability, suggesting their usefulness for treating or diagnosing MERS.
The problems addressed arise from the high mortality rate and severe respiratory symptoms caused by MERS-CoV. Current treatments, such as interferon and ribavirin, have side effects and lack efficacy in clinical use, especially in severe patients. There is an urgent need for biologically safe therapeutic antibodies that effectively suppress virus proliferation and can be used in severe, immunocompromised, or underlying disease patients.
The invention provides not only monoclonal antibodies but also their variable region sequences, genes encoding these regions, recombinant vectors, host cells expressing these antibodies, compositions for prevention, treatment, or diagnosis of MERS, and kits for detecting MERS antigens. Methods of use include administering the antibodies or their variable regions to subjects for treatment, prevention, or diagnosis, highlighting the therapeutic and diagnostic potential of these antibodies against MERS-CoV.
Claims Coverage
The claims include methods for treating and detecting MERS and compositions involving specific monoclonal antibodies, with six main inventive features identified corresponding to antibody sequences and their applications.
Monoclonal antibody comprising specific heavy and light chain variable regions for treating MERS
A method for treating MERS comprising administering a monoclonal antibody that binds specifically to the MERS-CoV spike protein. The antibody includes a human immunoglobulin heavy chain constant region, a light chain constant region, and specific combinations of heavy chain variable region (VH) and light chain variable region (VL) sequences selected from particular SEQ ID NO pairs (1&2, 3&4, 9&10, 11&12, 19&20, 21&22).
Use of monoclonal antibody targeting MERS-CoV spike protein for antigen detection
A method for detecting MERS-CoV antigen by performing an antigen-antibody reaction using a monoclonal antibody with binding specificity to the MERS-CoV spike protein, comprising human immunoglobulin heavy and light chain constant regions and specific VH and VL combinations as listed above.
Contacting MERS-CoV with a monoclonal antibody comprising defined variable regions
A method comprising contacting MERS-CoV with a monoclonal antibody having specific VH and VL combinations, each corresponding to specific SEQ ID NOs (as above), and including human immunoglobulin heavy and light chain constant regions.
Monoclonal antibody having specific heterologous human IgG constant regions and variable regions
A monoclonal antibody that binds specifically to the MERS-CoV spike protein and comprises heterologous human immunoglobulin G heavy chain constant regions, with variable regions (VH and VL) selected from specific SEQ ID NO combinations as identified.
Composition comprising the monoclonal antibody for binding MERS-CoV spike protein
A composition for binding MERS-CoV spike protein comprising an effective amount of the monoclonal antibody (as above) disposed in an excipient.
Specificity of antibodies to the MERS-CoV spike protein sequence and region
Claims specify that the MERS-CoV spike protein comprises the amino acid sequence represented by SEQ ID NO: 23, and that the antibody variable regions bind specifically to the 1st to 757th amino acids from the N-terminus of the spike protein.
The claims cover therapeutic, diagnostic, and detection methods employing monoclonal antibodies with defined heavy and light chain variable regions specifically binding the MERS-CoV spike protein, compositions comprising these antibodies, and their use in binding the spike protein sequence represented by SEQ ID NO: 23.
Stated Advantages
The monoclonal antibodies have excellent attachment force with respect to a full-length MERS-CoV spike protein and the S1 domain, and some to the RBD antigen.
Certain antibodies exhibit neutralizing capacity against MERS pseudovirus and MERS-CoV, including broad neutralization across strains.
The monoclonal antibodies exist in a particular monomeric form and demonstrate excellent physical stability.
These traits indicate usefulness of the antibodies for treating or diagnosing MERS.
Documented Applications
Use of monoclonal antibodies for prevention, treatment, and diagnosis of Middle East respiratory syndrome.
A diagnostic kit for detection or quantification of MERS-CoV antigens using the monoclonal antibodies.
Methods of administering monoclonal antibodies or their variable regions to subjects for MERS prevention, treatment, or diagnosis.
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