Broadly Cross-Reactive Neutralizing Antibodies against Human Immunodeficiency Virus Selected by ENV-CD4-CO-Receptor Complexes
Description of Invention:
This invention provides a novel anti-HIV human monoclonal antibody named X5. This antibody demonstrates promise over conventional anti-HIV antibodies because the X5 antibody exhibits a unique binding activity compared to its counterparts. It has been established that the initial stage of HIV-1 entry into cells is mediated by a complex between the viral envelope glycoprotein (Env) such as gp120-gp41, a receptor CD4 and a co-receptor CCR5. The X5 antibody binds to an epitope on gp120 that is induced by interaction between gp120 and the receptor CD4 and enhanced by the co-receptor CCR5. The X5 antibody also shows strong activity at very low levels (in the range from 0.0001 - 0.1 Mg/ml concentration is dependent on the isolate). Because it is a human antibody, it can be administered directly into patients so that it is an ideal candidate for clinical trials. It also can be easily produced because it was obtained by screening of phage display libraries and its sequence is known. Finally, since it has neutralized all virus envelope glycoproteins, including those from primary isolates of different clades, the epitope is highly conserved and resistance is unlikely to develop. Therefore, this antibody and/or its derivatives including fusion proteins with CD4 are good candidates for clinical development.
Applications:
Antibody for HIV research, diagnostics and therapeutic development
Development Status:
Preclinical data is available at this time.
Inventors:
Dimiter Dimitrov (NCI) Xiadong Xiao (NCI) Yuuei Shu (NCI) Sanjay Phogat (NIAID) et al.
Patent Status:
DHHS Reference No. E-130-2001/0 --
Patent Cooperation Treaty Application No. PCT/US02/33165 filed 16 Oct 2002
National Stage Filing in United States, India, Canada, Australia, Europe
Licensing Status: Available for licensing and commercial development, excluding the field of use of the development of the PEGylated X5, PEGylated X5 derivatives, mutants of PEGylated X5 or a derivative.
Collaborative Research Opportunity:
The NCI Center for Cancer Research Nanobiology Program (CCRNP) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antibodies for HIV research, diagnostics and therapeutic development. Please contact John D. Hewes, Ph.D. at (301) 435-3121 or hewesj@mail.nih.gov for more information.
For Additional Information Please Contact: Sally Hu PhD MBA
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5606
Email: hus@mail.nih.gov
Fax: (301) 402-0220
