Combination therapy is a fast-growing strategy to maximize therapeutic benefits to patients. Co-formulation of two or more therapeutic proteins has advantages over the administration of multiple medications, including reduced medication errors and convenience for patients. Characterization of co-formulated biologics can be challenging due to the high degree of similarity in the physicochemical properties of co-formulated proteins, especially at different concentrations of individual components. We present the results of a deamidation study of one monoclonal antibody component (mAb-B) in co-formulated combination antibodies (referred to as COMBO) that contain various ratios of mAb-A and mAb-B. A single deamidation site in the complementarity-determining region of mAb-B was identified as a critical quality attribute (CQA) due to its impact on biological activity. A conventional charge-based method of monitoring mAb-B deamidation presented specificity and robustness challenges, especially when mAb-B was a minor component in the COMBO, making it unsuitable for lot release and stability testing. We developed and qualified a new, quality-control-friendly, single quadrupole Dalton mass detector (QDa)–based method to monitor site-specific deamidation. Our approach can be also used as a multi-attribute method for monitoring other quality attributes in COMBO. This analytical paradigm is applicable to the identification of CQAs in combination therapeutic molecules, and to the subsequent development of a highly specific, highly sensitive, and sufficiently robust method for routine monitoring CQAs for lot release test and during stability studies.

Taekyun Kim, Evdokia Sotirova, Anthony Shannon, Vassia Atanassova, Krassimir Atanassov, and Lee-Chae Jang. IJFIS 2018;18:190-5. https://doi.org/10.5391/IJFIS.2018.18.3.190

This note considers some real and complex extensions and generalizations of the Leonardo sequence, which is embedded within each of these two types of intriguing sequences, intriguing because there are still some unanswered questions. The connections between inhomogeneous and homogeneous forms are used as examples of a possible reason that the Leonardo sequences have been, in a sense, historically neglected.

Recursive sequences with gaps have been studied previously. This paper considers some elementary properties of such sequences where the gaps have been created on a regular basis from sequence to sequence – ‘discatenated’ (systematic gaps) and ‘lacunary’ (general gaps). In particular, their generating functions are developed in order to open up their general terms and relations with other properties.