Monospecific and Bispecific Human Monoclonal Antibodies Targeting IGF-II


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.

Potential Commercial Applications: Competitive Advantages:
  • 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
 
  • 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


Related Inventoion(s):
E-336-2005/0
E-217-2005/2
E-232-2009/0
E-068-2011/0


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


Intellectual Property:
US Application No. 61/548,164
PCT Application No. PCT/US2012060443

Collaboration 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.


Licensing Contact:
Whitney Hastings ,
NIH Office of Technology Transfer
Email: hastingw@mail.nih.gov
Phone: 301-451-7337

OTT Reference No: E-212-2011/0

Updated: Jan-17-2012