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Monospecific and Bispecific Human Monoclonal Antibodies Targeting IGF-II

Posted Jan 16 2012 7:00pm

Description of Invention:
The type 1 insulin-like growth factor (IGF) receptor (IGF1R) is over-expressed by many tumors and mediates proliferation, motility, and protection from apoptosis. Agents that inhibit IGF1R expression or function can potentially block tumor growth and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed by multiple tumor types. Previous studies indicate that inhibition of IGF-I, and/or IGF-II binding to its cognizant receptor negatively modulates signal transduction through the IGF pathway and concomitant cell proliferation and growth. Therefore, use of humanized or fully human antibodies against IGFs represents a valid approach to inhibit tumor growth. The present invention discloses two monoclonal antibodies, designated m610.27 and m630, and a bispecific monoclonal antibody, m660, generated by linking domains from m610.27 and m630. All three antibodies display high affinities for IGF-I and IGF-II in the pM to nM range. The antibodies inhibited signal transduction mediated by the IGF-1R interaction with IGF-I and IGF-II and blocked phosphorylation of IGF-IR and the insulin receptor. m610.27 and m630 are the first pair of human antibodies that target nonoverlapping epitopes on IGF-II. All three antibodies in an IgG1 or IgG1-like format could lead to irreversible elimination of IGF-II from circulation making it a viable candidate for cancer treatment.

Applications:
  • Therapeutic for the treatment of various human diseases associated with aberrant cell growth and motility such as breast, prostate, and leukemia cancers
  • Research reagent to study IGF-I and/or IGF-II binding and its association with tumor growth


Advantages:
  • m610.27 and m630 are the first characterized antibodies that target nonoverlapping epitopes on IGF-II
  • m660 was generated from two domains; one each from m610.27 and m630
  • small size of the m610.27 and m630 domains prevent overlapping in binding to IGF-II


Development Status:
  • Pre-clinical
  • In vitro data available


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


Patent Status:
HHS, Reference No. E-212-2011/0
US, Application No. 61/548,164 filed 17 Oct 2011


Related Technologies:
US, Patent No. 7,824,681, Issued 02 Nov 2010, Reference No. E-217-2005/2
US, Application No. 12/889,345 filed 23 Sep 2010, Reference No. E-217-2005/2
US, Patent No. 8,071,323, Issued 06 Dec 2011, Reference No. E-336-2005/0
PCT, Application No. PCT/US2010/051784 filed 07 Oct 2010, Reference No. E-232-2009/0
US, Application No. 61/474,664 filed 12 Apr 2011, Reference No. E-068-2011/0
PCT, Application No. PCT/US2007/066180 filed 06 Apr 2007, Reference No. E-336-2005/0
US, Application No. 61/249,476 filed 07 Oct 2009, Reference No. E-232-2009/0


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 this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov .


For Licensing 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: 2351

Updated: 01/2012

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