Dr. Jason Tonillo

Senior scientist in ADCs and targeted NBE therapeutics, Global R&D, Merck KGaA, Darmstadt, Germany
Dr. Jason Tonillo headshot

Project Goal

Characterize antibodies and antibody drug conjugates (ADCs) in terms of amino acid sequence, drug-to-antibody ratio (DAR) and post-translational modifications.

The Challenges

  • Establishing a native mass spectrometry method that maintains the quaternary structure of interchain cysteine conjugated ADCs.
  • Establishing a label-free method for the quantification of serum incubated ADCs.

The solution

  • Top-down approach for quick confirmation of proteins, identification of common post-translational modifications and determination of the DAR.
  • Bottom-up mass spectrometry for in-depth analysis of the amino acid sequence and site localization of modifications.
  • BioPharmaView™ Software automatically calculates the DAR and creates a report, which can be sent to customers without further manual changes.

The outcome

  • Generic method for routine analysis of the DAR, regardless of antibody, linker and payload.
  • Quick confirmation of the protein identity of small-scale expressions.
  • "The 6600+ system provides important data for the development of new biological drugs.”

Goals

Achieve in-depth characterization of antibodies and ADCs

SCIEX products

  • TripleTOF® 6600+ LC-MS/MS System
  • X500R QTOF System