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High-Affinity Rabbit Monoclonal Antibodies To Mesothelin for Treatment of Cancer

Posted Jan 23 2013 7:00pm

Description of Invention:
Mesothelin is a cell surface protein that is highly expressed in aggressive cancers, such as malignant mesothelioma, ovarian cancer and pancreatic cancer. Because of this selective expression, mesothelin is an excellent candidate for targeted therapeutics, such as monoclonal antibodies (mAbs) and chimeric molecules. Current anti-mesothelin therapeutic mAb candidates bind to an epitope in Region I of mesothelin. Unfortunately, Region I contains the interaction site MUC16/CA125, a mesothelin-interacting protein that is present in the serum of patients with mesothelin-related cancers. Because the current therapeutic mAb candidates must compete with MUC16/CA125 for binding to mesothelin, they may not reach their full therapeutic potential due to interference.

In order to address this concern, NIH inventors generated several rabbit mAbs that recognize unique epitopes of mesothelin: (1) YP223, which recognizes region II; (2) YYP218, which recognizes region III; and (3) YP3 which recognizes a native conformation epitope of mesothelin. These mAbs bind to mesothelin with sub-nanomolar affinity and are not out-competed for binding by the current anti-mesothelin therapeutic mAb candidates or MUC16/CA125. This strong binding affinity for an alternative binding site on mesothelin suggests that these mAbs are excellent therapeutic candidates.

  • Therapeutic use, such as treatment of mesothelin-expressing cancers as a stand-alone mAbs or as a mAb-drug conjugate (e.g., an immunotoxin).
  • Diagnosis of mesothelin-expressing cancers.
  • Antibody-related research use, including immunoprecipitation, western blot analysis, immunohistochemistry, ELISA, etc.

  • Binding of new epitope on mesothelin may improve therapeutic applications due to non-competition from serum proteins.
  • High binding affinity (sub-nanomolar levels) also increases chances of binding and subsequent therapeutic activity.

Development Status:
  • Early-stage
  • In vitro data available

Ira H Pastan (NCI)
Mitchell Ho (NCI)
Yen T Phung (NCI)
Yifan Zhang (NCI)

Patent Status:
HHS, Reference No. E-198-2012/0
US, Application No. 61/691,719 filed 21 Aug 2012

Related Technologies:
US, Patent No. 6,809,184, Issued 26 Oct 2004, Reference No. E-021-1998/0
US, Patent No. 7,081,518, Issued 25 Jul 2006, Reference No. E-139-1999/0
US, Application No. 13/259,138 filed 23 Mar 2010, Reference No. E-091-2009/0
US, Application No. 60/160,071 filed 27 May 1999, Reference No. E-139-1999/0
US, Application No. 61/162,778 filed 24 Mar 2009, Reference No. E-091-2009/0

Relevant Publication:
  1. Ho M. [ PMID 21942912 ]

Collaborative Research Opportunity:
The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize new monoclonal antibodies to unique domains of mesothelin for cancer therapy or diagnostics. For collaboration opportunities, please contact John Hewes, Ph.D. at .

For Licensing Information Please Contact:
David Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-4632
Fax: 301-402-0220

Ref No: 2518

Updated: 01/2013

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