title: Detection and consequences of recombinant protein isoforms: implications for biological potency.
abstract: Various types of structural variants have been observed in recombinant DNA - derived products. These isoforms include variations in post translational carbohydrate modifications where variations in site occupancy or unoccupied sites may occur. In addition, varying degrees of C-terminal processing and N-terminal substitutions have been observed. Isoforms may also be generated during processing and can include aggregated and/or chemically modified forms of the protein. Sophisticated analytical techniques exist for the identification and characterization of these structural variants. Several strategies have been used to isolate or enrich the isoform before molecular characterization. However, the effect these structural variations have on the biological activity of the product is less well understood. This may, in part, be due to the specificity and variability of the bioassay employed. This presentation describes the isolation and characterization of specific molecular isoforms for a monoclonal antibody product as well as an assessment of effects on biological activity.
authors: GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 10496-0939, USA. Marcia_m_federici@sbphrd.com
authors: M M
authors: MM
authors: Federici
authors: K
authors: K
authors: Venkat
authors: N
authors: N
authors: Bam
authors: K
authors: K
authors: Patel
authors: P R
authors: PR
authors: Dal Monte
authors: B
authors: B
authors: Fernie
authors: P
authors: P
authors: Hensley
authors: S
authors: S
authors: Carr
authors: J
authors: J
authors: Baldoni
authors: A
authors: A
authors: Truneh
authors: J
authors: J
authors: Erickson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D004345:Drug Industry / Q000379:methods; D004586:Electrophoresis; D006801:Humans; D013058:Mass Spectrometry; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D011994:Recombinant Proteins