Monoclonal antibodies against orthopoxviruses
Inventors
Chen, Zhaochun • Earl, Patricia • Moss, Bernard • Emerson, Suzanne U. • Purcell, Robert H.
Assignees
US Department of Health and Human Services
Publication Number
US-8404818-B2
Publication Date
2013-03-26
Expiration Date
2026-12-22
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Abstract
The present invention relates to monoclonal antibodies that bind or neutralize Orthopoxviruses. The invention provides such antibodies, fragments of such antibodies retaining B5 or A33 binding ability, fully human antibodies retaining B5 or A33 binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
Core Innovation
The invention relates to monoclonal antibodies that bind or neutralize Orthopoxviruses, including antibodies and fragments retaining B5 or A33 binding ability, fully human antibodies, pharmaceutical compositions including such antibodies, isolated nucleic acids encoding them, and host cells transformed therewith. It provides for prophylactic, therapeutic, and diagnostic methods employing these antibodies and nucleic acids.
The problem being addressed is the need for effective treatments against Orthopoxvirus infections, including smallpox and vaccinia virus complications, given the limitations of existing vaccines and treatments. Current vaccinia immune globulin (VIG) used to treat vaccine-related complications has variable potency and potential infectious risks.
The invention solves this by producing novel high-affinity, human-like monoclonal antibodies derived from chimpanzees vaccinated with vaccinia virus, which target the B5 and A33 proteins of Orthopoxviruses. These antibodies neutralize viruses effectively, provide superior protection at lower doses, demonstrate therapeutic efficacy in animal models, and can overcome limitations of existing VIG treatments.
Claims Coverage
The patent includes multiple inventive features related to fully human or humanized chimpanzee monoclonal antibodies targeting the A33 antigen, their fragments, deposited antibodies, and compositions, as well as methods of use.
Monoclonal antibody binding A33 antigen
A substantially pure polypeptide comprising a fully human or humanized chimpanzee monoclonal antibody that binds A33 antigen, comprising specific heavy and light chain CDR regions defined by SEQ ID NOs: 35, 37, 39, 43, 45, 47 or alternatively 51, 53, 55, 59, 61, 63.
Antibody fragments
The monoclonal antibody may comprise a Fd fragment or a Fab fragment.
Deposited antibody
An anti-vaccinia virus A33 6C monoclonal antibody deposited with ATCC as accession number PTA-7323.
Pharmaceutical and diagnostic preparations
Pharmaceutical and diagnostic compositions comprising the monoclonal antibody that binds A33 antigen as defined above.
Monoclonal antibodies binding conformational epitopes
Monoclonal antibodies binding conformational epitopes of A33 antigen to which the specified monoclonal antibodies bind.
Methods of inhibiting Orthopoxvirus infection
Methods for inhibiting Orthopoxvirus infection by administering an effective amount of the pharmaceutical preparations comprising the monoclonal antibody binding A33 antigen.
Methods of diagnosis and detection of Orthopoxvirus
Methods for diagnosis or detection of Orthopoxvirus infection by administering or contacting with the diagnostic preparation comprising the monoclonal antibody binding A33 antigen and detecting antibody binding.
The claims cover monoclonal antibodies specifically binding A33 antigen with defined CDR sequences, their functional fragments, deposited antibodies, related pharmaceutical and diagnostic compositions, and methods for treating and diagnosing Orthopoxvirus infections using these compositions.
Stated Advantages
Chimpanzee/human monoclonal antibodies provide superior protection with lower doses and higher safety profiles than vaccinia immune globulin (VIG).
The antibodies neutralize vaccinia and variola viruses effectively both in vitro and in vivo.
They offer therapeutic benefit when administered before and even two days after infection.
They overcome limitations of VIG such as low neutralizing activity and potential transmission of infectious agents.
Documented Applications
Prophylactic and therapeutic treatment of Orthopoxvirus infections, including complications of smallpox vaccination and infections caused by vaccinia virus and variola virus.
In vitro and in vivo diagnostic methods for detecting Orthopoxvirus infection by utilizing monoclonal antibodies specific to B5 or A33 antigens.
Use in immunoprophylaxis and immunotherapy of Orthopoxvirus infections in humans and animals.
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