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Human Single-domain Antibodies (dAbs) Against Insulin-like Growth Factor 1 Receptor (IGF-1R) or Its Ligands, IGF-1 and IGF-2

Posted Jul 01 2010 5:00pm

Description of Invention:
Insulin-like growth factor (IGF) mediated signaling has been implicated in the development of several epithelial cancers, such as prostate, breast, and colorectal cancers. This technology consists of human single domain antibodies (dAbs) that bind to human insulin-like growth factor 1 receptor (IGF-1R) or its ligands, IGF-1 and IGF-2. These dAbs are comprised of only a single variable domain of an antibody with a human framework and three complementarity determining regions (CDRs). Several of these antibodies inhibit the IGF signaling pathway so they may be therapeutic candidates for the treatment of IGF-related cancers.

Applications:
  • A cancer therapeutic agent that inhibits the IGF-mediated signaling pathway
  • A diagnostic employing the detection of insulin-like growth factor 1 receptor (IGF-1R) or its ligands, IGF-1 and IGF-2, in a sample


Advantages:
  • dAbs are about 10-fold smaller than IgG antibodies and exhibit dramatically increased penetration into solid tumors.
  • dAbs can be produced in high yields at low cost, have favorable biophysical properties, and are well suited to engineering.
  • dAbs are bioactive as monomers or can be linked into larger molecules to create drugs with prolonged serum half-lives or other pharmacological activities.
  • dAbs can be fused to other polypeptides or other drugs to provide fusion proteins or conjugates.
  • Human framework reduces potential for host immune reactions.


Development Status:
Early-stage development

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


Patent Status:
HHS, Reference No. E-232-2009/0
US, Application No. 61/249,476 filed 07 Oct 2009


Relevant Publication:
  1. Chen W, Zhu Z, Feng Y, Dimitrov DS. A large human domain antibody library combining heavy and light chain CDR3 diversity. Mol Immunol. 2010 Jan;47(4):912-921. [ PubMed: 19883941 ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The Center for Cancer Research Nanobiology Program (CCRNP), National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the dAbs that exhibit potent inhibitory activities against the human IGF signaling pathway. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Diagnostics
Cancer - Therapeutics



For Additional Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 2128

Updated: 07/2010

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