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


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


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


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

OTT Reference No: E-212-2011/0

Updated: 01/17/2012