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High Diversity/High Affinity Domain Antibody Library

Posted Jul 16 2009 5:00pm

Description of Invention:
Available for licensing and commercial development is a highly diverse domain antibody (dAb) library providing antibodies that bind with high affinity to variety of antigen targets. Antibody diversity is inherently limited by using only three CDRs of either light chain variable domain (LCDRs) or heavy chain variable domain (HCDRs). This novel dAb library is designed using light chain variable domain 3 (LCDR3) and heavy chain variable domain (HCDR3), which are of primary importance for creating binding site diversity in the human immune system. The library contains 2.5 x 1010 dAbs. Human naturally occurring LCDR3s were grafted onto HCDR1 of m0. These antibodies are of very small size (15-17 kDa), high stability and can be expressed at high levels as monomers. The library can be used for the selection of antibodies to any antigen including cancer and viral antigens and exhibit such properties as good penetration, stability, solubility, high levels of expression (at potentially low cost), and low level of immunogenicity or toxicity.

Applications:
  • Cancer
  • Infectious disease
  • Therapeutics
  • Diagnostics
  • Research reagents
  • Research tools
  • Library panning


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


Patent Status:
HHS, Reference No. E-216-2009/0

Research Tool -- patent protection is not being pursued for this technology

Relevant Publication:
  1. P Jirholt et al. Exploiting sequence space: shuffling in vivo formed complementarity determining regions into a master framework. Gene 1998 Jul 30;215(2):471-476. [ PubMed abs ]
  2. Y Reiter et al. An antibody single-domain phage display library of a native heavy chain variable region: isolation of functional single-domain VH molecules with a unique interface. J Mol Biol. 1999 Jul 16;290(3):685-698. [ PubMed abs ]
  3. L Riechmann and S Muyldermans. Single domain antibodies: comparison of camel VH and camelised human VH domains. J Immunol Methods 1999 Dec 10;231(1-2):25-38. [ PubMed abs ]
  4. E Söderlind et al. Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat Biotechnol. 2000 Aug;18(8): 852-856. [ PubMed abs ]
  5. LJ Holt et al. Domain antibodies: proteins for therapy. Trends Biotechnol. 2003 Nov;21(11): 484-490. [ PubMed abs ]
  6. W Chen et al. Construction of a large phage-displayed human antibody domain library with a scaffold based on a newly identified highly soluble, stable heavy chain variable domain. J Mol Biol. 2008 Oct 10;382(3):779-789. [ PubMed abs ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute, CCR, CCRNP is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this domain antibody library. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Cancer
Cancer - Research Materials
Infectious Diseases
Infectious Diseases - Research Materials
Gene Based Therapies
Gene Based Therapies - Research Materials
Internal Medicine
Internal Medicine - Research Materials
Miscellaneous
Central Nervous System
Central Nervous System - Research Materials
Ophthalmology
Ophthalmology - Research Materials
Research Materials
Dental Technology
Dental Technology - Research Materials



For Additional Information Please Contact:
Michael Shmilovich Esq.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: shmilovm@mail.nih.gov
Phone: 301-435-5019
Fax: 301-402-0220


Ref No: 1986

Updated: 07/2009

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