title: Technical decision making with higher order structure data: higher order structure characterization during protein therapeutic candidate screening.
abstract: Protein therapeutics differ considerably from small molecule drugs because of the presence of higher order structure (HOS), post-translational modifications, inherent molecular heterogeneity, and unique stability profiles. At early stages of development, multiple molecular candidates are often produced for the same biological target. In order to select the most promising molecule for further development, studies are carried out to compare and rank order the candidates in terms of their manufacturability, purity, and stability profiles. This note reports a case study on the use of selected HOS characterization methods for candidate selection and the role of HOS data in identifying potential challenges that may be avoided by selecting the optimal molecular entity for continued development.
authors.affiliation: Attribute Sciences, Amgen Inc., Thousand Oaks, California, 91320.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Jiang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Li
authors.forename: Jenny
authors.initials: J
authors.lastname: Li
authors.forename: John P
authors.initials: JP
authors.lastname: Gabrielson
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D003661:Decision Support Techniques; D055808:Drug Discovery / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D010316:Particle Size; D066329:Protein Aggregates; D011487:Protein Conformation; D055550:Protein Stability; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products; D066329:Protein Aggregates
keywords: CD; DLS; DSC; SEC; biophysical characterization; candidate selection; higher order structure; protein; stability