Monoclonal Antibodies That Bind or Neutralize Dengue Virus
Description of Invention:
Among the arthropod-borne flaviviruses, the four dengue virus serotypes, dengue type 1 virus (DENV-1), dengue type 2 virus (DENV-2), dengue type 3 virus (DENV-3), and dengue type 4 virus (DENV-4 are most important in terms of human morbidity and geographic distribution. Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitoes are abundant. Dengue infection produces fever, rash, and joint pain in humans. A more severe and life-threatening form of dengue, characterized by hemorrhagic fever and hemorrhagic shock, has occurred with increasing frequency in Southeast Asia and Central and South America, where all four dengue virus serotypes circulate. A safe and effective vaccine against dengue is currently not available. Passive immunization with monoclonal antibodies from non-human primates or humans represents a possible alternative to vaccines for prevention of illness caused by dengue virus.
The application claims monoclonal antibodies that bind or neutralize dengue type 1, 2, 3, and/or 4 viruses. The application also claims fragments of such antibodies retaining dengue virus-binding ability, fully human or humanized antibodies retaining dengue virus-binding ability, and pharmaceutical compositions including such antibodies. The application also claims isolated nucleic acids encoding the antibodies of the invention. Additionally, application claims prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
Application:
Prophylaxis against dengue serotypes 1, 2, 3 and 4.
Development Status:
Antibodies have been synthesized and preclinical studies have been performed.
Patent Status:
DHHS Reference No. E-066-2003/5 --
U.S. Patent Application No. 10/582,006 filed 07 Jun 2006
Canadian Patent Application No. 2548808 filed 03 Dec 2004
Relevant Publication: The antibodies are further described in:
R Men et al. Identification of chimpanzee Fab fragments by repertoire cloning and production of a full-length humanized immunoglobulin G1 antibody that is highly efficient for neutralization of dengue type 4 virus. J Virol. 2004 May;78(9):4665-4674. [PubMed abs]
AP Goncalvez et al. Chimpanzee Fab fragments and a derived humanized immunoglobulin G1 antibody that efficiently cross-neutralize dengue type 1 and type 2 viruses. J Virol. 2004 Dec;78(23):12910-12918. [PubMed abs]
AP Goncalvez et al. Epitope determinants of a chimpanzee Fab antibody that efficiently cross-neutralizes dengue type 1 and type 2 viruses map to inside and in close proximity to fusion loop of the dengue type 2 virus envelope glycoprotein. J Virol. 2004 Dec;78(23):12919-12928. [PubMed abs]
AP Goncalvez et al. Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc Natl Acad Sci U S A. 2007 May 29;104(22):9422-9427. [PubMed abs]
Licensing Status: Available for exclusive or non-exclusive licensing.
Collaborative Research Opportunity:
The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Ching-Juh Lai at 301-594-2422 for more information.
For Additional Information Please Contact: Peter A. Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4646
Email: soukasp@mail.nih.gov
Fax: (301) 402-0220
