Abstract:
:Monoclonal antibodies play an increasingly important role for the development of new drugs across multiple therapy areas. The term 'developability' encompasses the feasibility of molecules to successfully progress from discovery to development via evaluation of their physicochemical properties. These properties include the tendency for self-interaction and aggregation, thermal stability, colloidal stability, and optimization of their properties through sequence engineering. Selection of the best antibody molecule based on biological function, efficacy, safety, and developability allows for a streamlined and successful CMC phase. An efficient and practical high-throughput developability workflow (100 s-1,000 s of molecules) implemented during early antibody generation and screening is crucial to select the best lead candidates. This involves careful assessment of critical developability parameters, combined with binding affinity and biological properties evaluation using small amounts of purified material (<1 mg), as well as an efficient data management and database system. Herein, a panel of 152 various human or humanized monoclonal antibodies was analyzed in biophysical property assays. Correlations between assays for different sets of properties were established. We demonstrated in two case studies that physicochemical properties and key assay endpoints correlate with key downstream process parameters. The workflow allows the elimination of antibodies with suboptimal properties and a rank ordering of molecules for further evaluation early in the candidate selection process. This enables any further engineering for problematic sequence attributes without affecting program timelines.
journal_name
MAbsjournal_title
mAbsauthors
Bailly M,Mieczkowski C,Juan V,Metwally E,Tomazela D,Baker J,Uchida M,Kofman E,Raoufi F,Motlagh S,Yu Y,Park J,Raghava S,Welsh J,Rauscher M,Raghunathan G,Hsieh M,Chen YL,Nguyen HT,Nguyen N,Cipriano D,Fayadat-Dilmadoi
10.1080/19420862.2020.1743053subject
Has Abstractpub_date
2020-01-01 00:00:00pages
1743053issue
1eissn
1942-0862issn
1942-0870journal_volume
12pub_type
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