Scalable and Cost-Effective Synthesis of a Linker for Bioconjugation with a Peptide and a Monoclonal Antibody

Javier Magano; Brian G. Conway; Douglas Farrand; Michael Lovdahl; Mark T. Maloney; Mark J. Pozzo; John J. Teixeira; John Rizzo; David Tumelty

doi:10.1055/s-0033-1340980

Synthesis, Table of Contents

Synthesis 2014; 46(10): 1399-1406
DOI: 10.1055/s-0033-1340980

paper

Scalable and Cost-Effective Synthesis of a Linker for Bioconjugation with a Peptide and a Monoclonal Antibody

Javier Magano*

^aChemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA Fax: +1(860)7158593 Email: Javier.Magano@Pfizer.com

,

Brian G. Conway

^aChemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA Fax: +1(860)7158593 Email: Javier.Magano@Pfizer.com

,

Douglas Farrand

^bAnalytical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA

,

Michael Lovdahl

^bAnalytical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA

,

Mark T. Maloney

^aChemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA Fax: +1(860)7158593 Email: Javier.Magano@Pfizer.com

,

Mark J. Pozzo

^cBiotherapeutics Pharmaceutical Sciences, Pfizer Worldwide Research & Development, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA

,

John J. Teixeira

^aChemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA Fax: +1(860)7158593 Email: Javier.Magano@Pfizer.com

,

John Rizzo

^dCovX Research, 9381 Judicial Drive, San Diego, CA 92121, USA

,

David Tumelty

^dCovX Research, 9381 Judicial Drive, San Diego, CA 92121, USA

› Author Affiliations

Abstract

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Abstract

An efficient, scalable, and cost-effective synthesis of a linker employed in a bioconjugation process with a peptide and a monoclonal antibody is presented. Several routes were investigated that resulted in the identification of a short synthesis to a key acid intermediate from inexpensive and readily available starting materials. The final coupling of this acid with an aniline to afford the desired linker has been optimized to produce multi-gram quantities of material for clinical studies. The very limited purifications needed for both intermediates and final product make this route amenable to scale.

Key words

linker - bioconjugation - peptide - monoclonal antibody - imide - azetidinone

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References

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