Session Chairs: Jason Rouse, Pfizer, Inc. and Christopher Yu, Genentech, a Member of the Roche Group

Session Description:

Mass spectrometry (MS) plays a pivotal role in the earliest stages of biotherapeutics development with respect to molecular design, developability and biotransformation. First, LC-MS characterization of multiple, early constructs in the ‘molecular design’ phase confirms that the intended molecule with the full-length sequence and expected posttranslational modifications was indeed expressed by the cell line and isolated by the purification process. For candidate molecules, ‘developability’ encompasses both predictive and experimental measures of physicochemical properties (including pharmacokinetics [PK]), which collectively enable selection of the optimal construct for more straightforward early- and late-stage product and process development, as well as clinical development (accounting for clinical indication, dosage, and administration route). As part of developability, stability studies combined with LC-MS/MS and biological activity measurements allow for early elucidation of structure-function relationships, in addition to the identification of potential sequence liabilities for subsequent engineering. Lastly, ‘biotransformation’, as monitored by LC-MS/MS, provides insight on how the molecular structure may change during in vivo circulation (after administration) to cause either a gain or loss of function (and/or altered circulating half-life). Biotransformation of therapeutic glycoproteins can involve protease fragmentation, glycosidase re-modelling, and increased deamidation, isomerization, oxidation, and glycation, in addition to removal of particular isoforms by certain receptors.

Session Speakers:

Intact Mass Characterization of Multi-Specific Therapeutic Antibodies

Kalie Mix, Sanofi

Antibody A In Vitro Biotransformation/Succinimide Characterization in Human Plasma by Immunoaffinity Purification (IA) – LC-MS and LC-MS/MS

Mei Han, Merck & Co., Inc.

Immunocapture Based LC/MS Investigation of Different Glycoform Clearance of a Biotherapeutic mAb in Human Serum

Jayanta Kishor Chakrabarty, Boehringer Ingelheim

Jason Rouse

Appearances

Session I: Molecular Design, Developability and Biotransformation

Session Chairs

Speakers