Discussion
Taken together, these data demonstrate that the tenecteplase copy Mingfule® has several meaningful fibrinolytic and biochemical differences compared with Metalyse®. This raises the question of whether data from clinical studies with one of the products can be generalized for all tenecteplase variants.
Methods
We have systematically analyzed and evaluated the biochemical and fibrinolytic differences between Metalyse® and Mingfule® using a wide range of routine quality testing assays, supplemented by mass spectrometry analysis and surface plasmon resonance assays. Additional host cell protein quantification and clot lysis testing following plasmin incubation over time were performed.
Results
Several key differences in biochemical composition and clot lysis activity were observed between the two tenecteplase variants. Versus Metalyse®, Mingfule® exhibited lower clot lysis activity and contained less of the two-chain form of tenecteplase. In addition, there were differences in sialic acid content, galactosylation, and fucosylation patterns, with Mingfule® exhibiting more bi- and less tri- and tetra-antennary glycosylation, leading to a different charge and size heterogeneity profile. Furthermore, Mingfule® displayed highly dissimilar binding to the three clearance receptors (LRP-1, ASGR, and mannose receptor) compared with Metalyse®. Purity analysis showed that Mingfule® contained a lower monomer content and, in contrast to Metalyse®, substantial amounts of host cell protein.