Framework Residue Substituted Humanized COL-1 Antibodies and Their Use
Description of Invention:
Carcinoembryonic antigen (CEA) has been found to be an important marker of colorectal cancer. CEA is expressed in 85% of all gastric cancers and may function as a metastatic potentiator of such cancers. In addition, it has been shown that CEA is up regulated when certain cancers are treated with standard chemotherapy drugs. A treatment modality that focuses specifically on CEA could be an effective way of treating many carcinomas, including colorectal, gastric, pancreatic, lung and breast cancers.
The present invention relates to humanized monoclonal antibodies that bind to CEA. Specifically, these antibody variants have amino acid substitutions in the heavy chain framework that reduces the likelihood of human anti-mouse antibodies (HAMA).
The original murine COL-1 antibody has been shown to be reactive to CEA without cross reactivity with other potential antigens of the CEA family: specifically Antigens NCA-1 and normal fecal antigen Ag1. The increased specificity to CEA and reduced human immunogenicity of these COL-1 humanized variants makes these antibodies attractive therapeutic and/or diagnostic compounds.
Patent Status:
DHHS Reference No. E-339-2004/0 --
U.S. Provisional Application No. 60/640,672 filed 30 Dec 2004
PCT Application No. PCT/US2005/047431 filed 30 Dec 2005, which published as WO 2006/074071 on 13 Jul 2006
Relevant Publication: The COL-1 antibody is described in the following background publications:
Gonzales NR, Padlan EA, De Pascalis R, Schuck P, Schlom J, and Kashmiri SV. SDR grafting of a murine antibody using multiple human germline templates to minimize its immunogenicity. Mol. Immunol. 41(9): 863-872, 2004.
De Pascalis R, Iwahashi M, Tamura M, Padlan EA, Gonzales NR, Santos AD, Giuliano M, Schuck P, Schlom J, and Kashmiri SV. Grafting of "abbreviated" complementarity-determining regions containing specificity-determining residues essential for ligand contact to engineer a less immunogenic humanized monoclonal antibody. J. Immunol. 169: 3076-3084, 2002.
Gonzales NR, Padlan EA, De Pascalis R, Schuck P, Schlom J, Kashmiri SV. Minimizing immunogenicity of the SDR-grafted humanized antibody CC49 by genetic manipulation of the framework residues. Mol. Immunol. 40: 337-349, 2003.
Licensing Status: In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.
Portfolios: Cancer
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Diagnostics Cancer -Therapeutics Cancer -Research Materials
For Additional Information Please Contact: Michelle A. Booden Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)451-7337
Email: boodenm@mail.nih.gov
Fax: (301) 402-0220
