Process Development and Structural Characterization of an Anti-Notch 3 Antibody–Drug Conjugate

2018 ◽  
Vol 22 (3) ◽  
pp. 286-295 ◽  
Author(s):  
Durgesh V. Nadkarni ◽  
Qingping Jiang ◽  
Olga Friese ◽  
Nataliya Bazhina ◽  
He Meng ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Process Development ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Notch 3 ◽  
Antibody Drug

scholarly journals Systematic LC/MS/MS Investigations for the IND-Enabling Extended Characterization of Antibody–Drug Conjugate Modifications

Antibodies ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 40
Author(s):  
Thomas Linz ◽  
Dominick Yeo ◽  
Qiuting Hong ◽  
Wesley Zmolek ◽  
Jesse McFarland ◽  
...  
Keyword(s):  
Small Molecule ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Liquid Chromatography Tandem Mass ◽  
Molecular Components ◽  
Mass Shifts ◽  
Composition Changes ◽  
Antibody Drug

We hypothesized that systematic liquid chromatography-tandem mass spectrometry investigations of an antibody–drug conjugate (ADC), its small and large molecular components, and surrogate small-molecule conjugates might comprise a simple and efficient approach for the extended characterization of ADCs. Furthermore, we envisioned that results from this work might allow us to assign specific composition changes in the ADC based on monoisotopic mass shifts of conjugatable modifications as detected in the surrogate small-molecule conjugates. We tested our hypothesis with a case study using an aldehyde-tag-based ADC conjugated to a noncleavable linker bearing a maytansine payload. Nearly quantitative bioconversion from cysteine to formylglycine was observed in the monoclonal antibody, and bioorthogonal conjugation was detected only on the formylglycine residues in the ADC. Using our method, both conjugatable and nonconjugatable modifications were discovered in the linker/payload; however, only conjugatable modifications were observed on the ADC. Based on these results, we anticipate that our approach to systematic mass spectrometric investigations can be successfully applied to other ADCs and therapeutic bioconjugates for investigational new drug (IND)-enabling extended characterization.

scholarly journals Preclinical Characterization of an Antibody–Drug Conjugate Targeting CS-1 and the Identification of Uncharacterized Populations of CS-1–Positive Cells

2020 ◽  
Vol 19 (8) ◽  
pp. 1649-1659
Author(s):  
Ruoyan Chen ◽  
Saravanan Rajan ◽  
Michael G. Overstreet ◽  
Elaine M. Hurt ◽  
Suneetha B. Thomas ◽  
...  
Keyword(s):  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

Kinetic reaction modeling for antibody-drug conjugate process development

2019 ◽  
Vol 306 ◽  
pp. 71-80 ◽  
Author(s):  
Sebastian Andris ◽  
Jonathan Seidel ◽  
Jürgen Hubbuch
Keyword(s):  
Process Development ◽  
Antibody Drug Conjugate ◽  
Kinetic Reaction ◽  
Drug Conjugate ◽  
Antibody Drug

Abstract 1198: Characterization of a novel maytansinoid-antibody-drug conjugate targeting LAMP1 expressed at the surface of tumor cells

2016 ◽  
Author(s):  
Yves Baudat ◽  
Beatrice Cameron ◽  
Tarik Dabdoubi ◽  
Anne-Marie Lefebvre ◽  
Ana Merino-Trigo ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

Abstract 935: Generation and preclinical characterization of CD123-CPI antibody-drug conjugate (ADC)

2018 ◽  
Author(s):  
Yoon-Chi Han ◽  
Fan Jiang ◽  
Nicole Piche-Nicholas ◽  
Madan Katragadda ◽  
Nadira Prashad ◽  
...  
Keyword(s):  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

Characterization of antibody drug conjugate positional isomers at cysteine residues by peptide mapping LC–MS analysis

2015 ◽  
Vol 981-982 ◽  
pp. 9-13 ◽  
Author(s):  
Marie-Claire Janin-Bussat ◽  
Marina Dillenbourg ◽  
Nathalie Corvaia ◽  
Alain Beck ◽  
Christine Klinguer-Hamour
Keyword(s):  
Peptide Mapping ◽  
Cysteine Residues ◽  
Positional Isomers ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Ms Analysis ◽  
Antibody Drug
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