Research abstract

Article abstract


Nature Biotechnology 25, 1290 - 1297 (2007)
Published online: 14 October 2007 | doi:10.1038/nbt1345

Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin

Chengbin Wu1, Hua Ying1, Christine Grinnell2, Shaughn Bryant3, Renee Miller1, Anca Clabbers1, Sahana Bose1, Donna McCarthy1, Rong-Rong Zhu4, Ling Santora1, Rachel Davis-Taber1, Yune Kunes1, Emma Fung1, Annette Schwartz2, Paul Sakorafas1, Jijie Gu1, Edit Tarcsa2, Anwar Murtaza3 & Tariq Ghayur1


For complex diseases in which multiple mediators contribute to overall disease pathogenesis by distinct or redundant mechanisms, simultaneous blockade of multiple targets may yield better therapeutic efficacy than inhibition of a single target. However, developing two separate monoclonal antibodies for clinical use as combination therapy is impractical, owing to regulatory hurdles and cost. Multi-specific, antibody-based molecules have been investigated; however, their therapeutic use has been hampered by poor pharmacokinetics, stability and manufacturing feasibility. Here, we describe a generally applicable model of a dual-specific, tetravalent immunoglobulin G (IgG)-like molecule—termed dual-variable-domain immunoglobulin (DVD-Ig)—that can be engineered from any two monoclonal antibodies while preserving activities of the parental antibodies. This molecule can be efficiently produced from mammalian cells and exhibits good physicochemical and pharmacokinetic properties. Preclinical studies of a DVD-Ig protein in an animal disease model demonstrate its potential for therapeutic application in human diseases.

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  1. Department of Biologics, Abbott Bioresearch Center, 100 Research Drive, Worcester, Massachusetts 01605, USA.
  2. Department of Discovery Safety, Metabolism & Pharmacokinetics, Abbott Bioresearch Center, 100 Research Drive, Worcester, Massachusetts 01605, USA.
  3. Department of Pharmacology, Abbott Bioresearch Center, 100 Research Drive, Worcester, Massachusetts 01605, USA.
  4. Department of Process Sciences, Abbott Bioresearch Center, 100 Research Drive, Worcester, Massachusetts 01605, USA.

Correspondence to: Chengbin Wu1 e-mail: chengbin.wu@abbott.com



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