Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

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dc.contributor.authorMonroe, Dougald M.
dc.contributor.authorJenny, Richard J.
dc.contributor.authorVan Cott, Kevin E.
dc.contributor.authorBuhay, Shelly
dc.contributor.authorSaward, Laura L.
dc.date.accessioned2016-05-11T15:37:44Z
dc.date.available2016-05-11T15:37:44Z
dc.date.issued2016-2-21
dc.date.updated2016-05-09T08:38:37Z
dc.description.abstractThe goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed less than 0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97%γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX.
dc.description.versionPeer Reviewed
dc.identifier.citationDougald M. Monroe, Richard J. Jenny, Kevin E. Van Cott, Shelly Buhay, and Laura L. Saward, “Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph,” Advances in Hematology, vol. 2016, Article ID 7678901, 9 pages, 2016. doi:10.1155/2016/7678901
dc.identifier.urihttp://dx.doi.org/10.1155/2016/7678901
dc.identifier.urihttp://hdl.handle.net/1993/31295
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderCopyright © 2016 Dougald M. Monroe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.titleCharacterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph
dc.typeJournal Article
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