New Molecules for HIV Therapeutics: Fab, scFv, and Related Binding Molecules Specific for HIV-1 Rev
Posted Mar 29 2011 8:00pm
Description of Invention: The invention offered for licensing and commercial development is in the field of HIV therapeutics. More specifically, the invention relates to methods and compositions for treating and/or inhibiting HIV infection or any other lentivirus. The invention describes the identification, though phage display, of a chimeric rabbit/human anti-Rev Fab (SJS-R1) that can inhibit polymerization of the HIV Rev protein and thus inhibit its normal function in virus replication. The Fab binds with very high affinity to a conformational epitope in the N-terminal half of HIV-1 Rev. The corresponding single chain antibody (scFv) was also prepared and characterized. Methods of making and using SJS-R1 Fab and SJS-R1 scFv, and antibodies and antibody fragments that share at least one CDR with SJS-R1 Fab, are provided. Specific described methods include methods of preventing or reversing polymerization of HIV Rev, methods of reducing infectivity of replication of a lentivirus, inhibiting Rev function in a cell infected with a lentivirus, and methods of treating a disease or symptom associated with Rev expression in an animal.
Applications: HIV therapeutics
Advantages:
The invention utilizes a novel target and thus can be effective in conjunction with other HIV drugs.
The chimeric structure of the Fab makes it possible to produce it in rabbit in high yields while being readily applicable for human treatment.
Development Status: The therapeutic molecules have been produced and their strong affinity to Rev and its inhibitory effect on HIV proliferation was demonstrated.
Stahl SJ, Watts NR, Rader C, DiMattia MA, Mage RG, Palmer I, Kaufman JD, Grimes JM, Stuart DI, Steven AC, Wingfield PT. Generation and characterization of a chimeric rabbit/human Fab for co-crystallization of HIV-1 Rev. J Mol Biol. 2010 Apr 2;397(3):697-708. [ PubMed: 20138059 ]
DiMattia MA, Watts NR, Stahl SJ, Rader C, Wingfield PT, Stuart DI, Steven AC, Grimes JM. Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for binding to the Rev response element. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5810-5814. [ PubMed: 20231488 ]
Licensing Status: Available for licensing and commercial development.
Collaborative Research Opportunity: The National Institute of Arthritis and Musculoskeletal and Skin Diseases, Protein Expression Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the technology. Please contact Cecilia Pazman, Ph.D. at 301-402-5579 for more information.
For Licensing Information Please Contact: John Stansberry Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: js852e@nih.gov Phone: 301-435-5236 Fax: 301-402-0220
Description of Invention:
The invention offered for licensing and commercial development is in the field of HIV therapeutics. More specifically, the invention relates to methods and compositions for treating and/or inhibiting HIV infection or any other lentivirus. The invention describes the identification, though phage display, of a chimeric rabbit/human anti-Rev Fab (SJS-R1) that can inhibit polymerization of the HIV Rev protein and thus inhibit its normal function in virus replication. The Fab binds with very high affinity to a conformational epitope in the N-terminal half of HIV-1 Rev. The corresponding single chain antibody (scFv) was also prepared and characterized. Methods of making and using SJS-R1 Fab and SJS-R1 scFv, and antibodies and antibody fragments that share at least one CDR with SJS-R1 Fab, are provided. Specific described methods include methods of preventing or reversing polymerization of HIV Rev, methods of reducing infectivity of replication of a lentivirus, inhibiting Rev function in a cell infected with a lentivirus, and methods of treating a disease or symptom associated with Rev expression in an animal.
Applications:
HIV therapeutics
Advantages:
Development Status:
The therapeutic molecules have been produced and their strong affinity to Rev and its inhibitory effect on HIV proliferation was demonstrated.
Inventors:
Stephen J Stahl (NIAMS)
Patent Status:
HHS, Reference No. E-064-2011/0
US, Application No. 61/439,307 filed 03 Feb 2011
Relevant Publication:
Licensing Status:
Available for licensing and commercial development.
Collaborative Research Opportunity:
The National Institute of Arthritis and Musculoskeletal and Skin Diseases, Protein Expression Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the technology. Please contact Cecilia Pazman, Ph.D. at 301-402-5579 for more information.
Portfolios:
Infectious Diseases
Infectious Diseases - Therapeutics
For Licensing Information Please Contact:
John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: js852e@nih.gov
Phone: 301-435-5236
Fax: 301-402-0220
Ref No: 2242
Updated: 03/2011