Assessing Functional Similarity of Biosimilar ABP 654 and Ustekinumab in Samples from Patients with Crohn's Disease.

Purpose: ABP 654 is the first FDA-approved interchangeable biosimilar for ustekinumab reference product (RP). To support the totality of evidence (TOE), in vitro pharmacology studies were conducted in peripheral blood mononuclear cells (PBMCs) from healthy human donors and Crohn's disease (CD) patients to evaluate IL-23 and IL-12 inhibition by ABP 654 and ustekinumab RP relevant to the mechanism of action of chronic inflammation.

Methods: ABP 654 and ustekinumab RP were assessed using inhibition of IL-23 and IL-12-mediated IFN-γ release, signal transducer and activator of transcription (STAT)3 and STAT4 phosphorylation, and IL-17 release.

Analysis of human antibody IgG2 domains by reversed-phase liquid chromatography and mass spectrometry.

It has been well documented that papain cleaves an IgG1 molecule to release Fab and Fc domains; however, papain was found unable to release such domains from an IgG2. Here we present a new combinatory strategy to analyze the heterogeneity of the light chain (LC), single chain Fc (sFc), and Fab portion of the heavy chain (Fd) of an IgG2 molecule released by papain cleavage under mild reducing conditions. These domains were well separated on reversed-phase high performance liquid chromatography (RP-HPLC) and analyzed by in-line liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS).