Nanoantibodies as Therapeutics and Diagnostics

Background:
The National Cancer Institute Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize nanoantibodies as therapeutics or diagnostics.

The size and stability of antibodies used for diagnosis and therapy of diseases are critical for their efficacy. Small binding entities based on the heavy chain variable domain (V_H) have been developed from humans, but some may be unstable because they have evolved to interact with the light chain variable domain (V_L). Single domain antibodies from Camelid (nanobodies) are stable (naturally occurring as part of a heavy chain only antibody) but could be immunogenic in humans because are foreign proteins.

Technology:
This invention involves conceptually novel scaffolds based on human antibody constant domains in contrast to those described previously which are based on the antibody variable domains. In the naturally occurring full size antibodies the CH2 domains (CH3 for IgE and IgM) are only weakly interacting through carbohydrates; thus the CH2 domain could be appropriate scaffold for engineering human antibodies. These antibody domains can also confer some effector functions. The engineered CH2 domains (nanoantibodies) are highly soluble, very stable, monomeric, and can be expressed at high levels. The small size of the nanoantibodies ensures efficient penetration into solid tumors and lymphoid tissues where HIV replicates as well as increased efficacy against HIV and other viruses that are able to avoid neutralization by larger, naturally occurring antibodies. In addition to HIV and other infectious and immune diseases, this technology can be used to develop diagnostics and therapeutics for numerous diseases including cancer. Because these nanoantibodies are derived from human sequences, they are likely to have lower toxic and immunogenic effects.

Further R&D Needed:

• Testing of nanoantibodies for functional activity in animal models
• Conjugation of nanoliposomes and small molecule drugs to nanoantibodies

R&D Status: Proof of concept experiments has been completed.

IP Status: U.S. Provisional Application No. 61/063,245 filed 31 Jan 2008

Value Proposition Solution:

• Might produce small nanoantibodies that are effective against viruses unable to be neutralized by larger antibodies
• Development of stable, soluble, antibodies with lower toxic and immunogenic effects
• Ability to create high-affinity binders to many antigens of interest
• Potential for diagnosis and treatment of HIV, cancer, and numerous other diseases

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #644 JH

Posted 04/09/2008