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Human Antibodies and Fusion Proteins with Potent and Broad HIV-1 Neutralizing Activity

Posted Sep 27 2012 8:00pm

Description of Invention:
The inventions listed below provide multiple novel human anti-HIV-1 domain antibodies (m36 and its affinity- matured versions) and their fusion proteins with two-domain or single-domain human soluble CD4 (sCD4) that can potentially be used alone or synergistically with other anti-HIV-1 antibodies and antiretroviral drugs as therapeutics and/or preventatives for infection by different HIV-1 strains.

Some of the inventions listed below also describe some fusion proteins as vaccine immunogens that could elicit broadly neutralizing antibodies against HIV-isolates from different clades. One invention also describes the methods to prepare and use the immunogens in the vaccination for prevention of HIV-1 infections. More specifically, the later invention provides a vaccine composed of a primary immunogen and a secondary immunogen, and a method for making the vaccine which could be effective in eliciting desired broadly neutralizing antibodies. The primary immunogen could be effective in activating B cell receptors (BCRs) that are on the maturational pathways of the desired antibodies and have an intermediate degree of somatic mutational diversity. The secondary immunogen contains epitopes of the desired antibodies and could be effective in further diversifying the BCRs sufficiently to form mature BCRs that have the identical or substantially identical sequence as the desired antibodies.

Applications:
Treatment and prevention of HIV-1 infections.

Advantages:
  • Elicits broadly neutralizing antibodies against HIV-1 isolates from different clades.
  • Potentially elicits antibodies that are not regulated by tolerance mechanisms.
  • Novel methods to design vaccines for HIV-1 treatment and prevention.
  • May also be used for designing vaccines for cancer treatment.
  • Relatively small size allows for potential penetration into lymphoid tissues.


Development Status:
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Dimiter S Dimitrov (NCI)
Weizao Chen (NCI)


Patent Status:
HHS, Reference No. E-043-2008/0
US, Application No. 12/811,998 filed 07 Jul 2010
US, Application No. 13/123,659 filed 11 Apr 2011
PCT, Application No. PCT/US2011/037439 filed 20 May 2011
PCT, Application No. PCT/US2009/60303 filed 11 Oct 2009


Relevant Publication:
  1. Chen W, et al. [ PMID 18957538 ]
  2. Chen W, et al. [ PMID 21715496 ]
  3. Chen W, et al. [ PMID 20709110 ]
  4. Chen W, Dimitrov DS. [ PMID 19339949 ]


Collaborative Research Opportunity:
The NCI CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize m36, single domain sCD4, and related fusion proteins as candidate therapeutics against HIV-1. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov .


For Licensing Information Please Contact:
Sally Hu Ph.D., M.B.A.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 21,
Rockville, MD 20852
United States
Email: hus@mail.nih.gov
Phone: 301-435-5606
Fax: 301-402-0220


Ref No: 2482

Updated: 09/2012

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