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Biologics & Oligonucleotides

Biologic drugs include monoclonal antibodies, hormones, growth factors, enzymes, vaccines, oligonucleotides and other large molecule therapeutics. While the evaluation of drug-drug interactions (DDIs) with small molecule drugs is well established, it is an area of growing concern and investigation for biologic drugs. Our in-house research and development teams have presented research and developed assays to explore specific intersections of biologics and small molecules in the context of DDI. For more information about these services, visit our Biologic-Small Molecule DDI page.


Scientific Posters

Effects of Monocyte Chemoattractant Protein-1, Macrophage Inflammatory Protein-1α and Interferon-α2a on P450 Enzymes in Human Hepatocytes in Vitro

Some immunomodulatory drugs, such as tilsotolimod, stimulate the innate immune system to release cytokines that may change expression of drug-metabolizing enzymes. In drug development, regulation of multiple pro- and anti-inflammatory cytokines by Toll-like receptors (TLR) has gained attention in parallel to targeting the therapeutic potential of these receptors. The aim of this study was to establish whether MCP-1, MIP-1α or IFN-α2a were responsible for the effects of tilsotolimod-stimulated plasma on CYP1A2 and CYP2B6 mRNA and enzyme activity levels...

An FGF15/19-TFEB regulatory loop controls hepatic cholesterol and bile acid homeostasis

Bile acid synthesis plays a key role in regulating whole body cholesterol homeostasis. Transcriptional factor EB (TFEB) is a nutrient and stress-sensing transcriptional factor that...
Regulatory Documents

2020 FDA Draft Guidance, “Drug-Drug Interaction Assessment for Therapeutic Proteins Guidance for Industry”

In August 2020, the FDA released the draft guidance for industry to evaluate therapeutic proteins for drug-drug interaction (DDI) potential using a risk-based approach.  ...

Effects of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and interferon-α2a on P450 enzymes in human hepatocytes in vitro

Maciej Czerwiński, Krystal Gilligan, Kevin Westland, Brian W. Ogilvie Some immunomodulatory agents stimulate the release of cytokines capable of suppressing P450 enzymes and potentially affecting pharmacokinetics of coadministered medications. Cytokines...
Scientific Posters

Human mAb stability and cytotoxicity in rat hepatocytes with a surrogate peptide approach

Evaluating stability and cytotoxicity ofHuman monoclonal antibody in cultured rat hepatocytes with a surrogate peptide approach Presented at the 12th International ISSX Meeting in Portland,...
Scientific Posters

Human monoclonal antibody stability in rat cell cultures using surrogate peptide LC-MS/MS

Evaluating stability ofHuman monoclonal antibody in rat cell cultures using a surrogate peptide LC-MS/MS approach Presented at the 67th ASMS Conference on Mass Spectrometry &...
Scientific Posters

An assessment of in vitro inhibition of CYPs, UGTs and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

Presented at the 2019 Marbach Castle Drug-Drug Interaction Workshop in Germany by Dr. Brian W. Ogilvie. Authors The poster presented information based on the publication:...

Can Interactions Between Therapeutic Proteins and Small Molecule Drugs Be Evaluated In Vitro?

The mechanisms of clearance for small molecule drugs and therapeutic proteins are fundamentally distinct and therefore therapeutic proteins are generally not...


In Vitro Evaluation of Immunomodulating Drugs as Perpetrators of Drug Interactions

Presenter: Dr. Maciej Czerwinski, SEKISUI XenoTech Director of Consulting Synopsis: On October 15th, 2018, SEKISUI XenoTech presented on “In Vitro Direct and Cytokine-Mediated Effects of Therapeutic Peptides...
Scientific Posters

Cytokine-mediated suppression of CYP enzymes by a toll-like receptor 9 agonist in hepatocytes

Presented at the American college of Toxicology (ACT) 39th Annual Meeting in Palm Beach, FL Full Title “Cytokine-mediated suppression of CYP enzymes by the toll-like...

October Presentations on In Vitro Effects of Biologics on CYP Enzymes and Regulatory DDI Guidances

On Oct. 15th at the Peptide ADME Discussion Group Workshop in Gothenburg, Sweden, Dr. Brian Ogilvie presented on In vitro Direct and Cytokine-Mediated...

Scientific Posters

Ultrasensitive quantitation assay of oligonucleotide therapeutics based on the PALSAR method

Akane Omori, Koichi Shibusawa, Kazuhiro Takeuchi, Akira Ideno Drug Development Solutions Center, Research & Development, SEKISUI MEDICAL CO., LTD. 2117 Muramatsu, Tokai, Ibaraki 319- 1182,...

Response to FDA Framework for Assessment of Drug-Drug Interactions for Therapeutic Proteins RFI and Comments

In July, Drs. Maciej Czerwinski, Director of Consulting, and Brian Ogilvie, Vice President of Scientific Consulting, submitted SEKISUI XenoTech’s comments in response to the...


An assessment of the in vitro inhibition of cytochrome P450 enzymes (CYP), UDP-glucuronsyltransferases (UGT) and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

Faraz Kazmi, Phyllis Yerino, Chase McCoy, Andrew Parkinson, David B Buckley and Brian W Ogilvie Oligonucleotides represent an expanding class of pharmacotherapeutics in development for...

Assess Catabolic Stability of Biologics & ADCs with Lysosomes – Characterized Test Systems

Originally published in tebu-bio’s Being Bioreactive. To purchase SEKISUI XenoTech’s products in the EU, please visit tebu-bio’s website.  Following up on my...


Direct and cytokine‐mediated effects of albumin‐fused growth hormone, TV‐1106, on CYP enzyme expression in human hepatocytes in vitro

Maciej Czerwiński, Immaculate Amunom, Victor Piryatinsky, Hussein Hallak, Yousif Sahly, Oren Bar‐Ilan, Paul Bolliger, Merav Bassan Some biologics can modulate cytokines that may lead to...

Direct and cytokine‐mediated effects of albumin‐fused growth hormone on CYP expression

Some biologics can modulate cytokines that may lead to changes in expression of drug‐metabolizing enzymes and cause drug‐drug interactions (DDI). DDI potential of TV‐1106—an albumin‐fused growth...

New Lysosome Catabolism Protocol and Tech Tips

A new guide outlining our IgG Catabolism Protocol as well as Lysosome and Tritosome Technical Tips is now available for those evaluating lysosomal stability...

Scientific Posters

Hepatocytes as the preferred test system to evaluate oligonucleotide-CYP Interactions in vitro

SEKISUI XenoTech previously examined the potential of oligonucleotides to inhibit cytochrome P450 (CYP) and reported that the phosphorothioate, but not phosphodiester, backboned molecules caused potent...

Tritosomes and Lysosomes for Characterization of Biologic Drugs

Presented by Dr. Chris Bohl, Manager of Techical Support, Products Synopsis Tritosomes and Lysosomes for Characterization of Biologic Drugs: Investigation of freshly purified rat tritosomes...
Scientific Posters

Effects of Albumin-Fused Human Growth Hormone TV-1106 on CYP Enzyme Expression in Human Hepatocytes

Drug-drug interactions involving therapeutic proteins that can modulate effects of cytokines and potentially impact cytochrome P450 (CYP) enzymes have been of increased interest to regulatory...
Scientific Posters

In Vitro System-Dependent Inhibition of CYPs, UGTs, and Drug Transporters by Oligonucleotides

We previously examined the cytochrome P450 (CYP) inhibition potential of oligonucleotides and reported that the phosphorothioate, but not phosphodiester, backboned molecules caused potent inhibition of...

Anti-CD28 Monoclonal Antibody-stimulated Cytokines Released from Blood Suppress CYP1A2, CYP2B6 and CYP3A4 in Human Hepatocytes In Vitro

Maciej Czerwiński, Faraz Kazmi, Andrew Parkinson, and David B. Buckley Like most infections and certain inflammatory diseases, some therapeutic proteins cause a cytokine-mediated suppression of...

Use of enzyme inhibitors to evaluate the conversion pathways of ester and amide prodrugs: A case study example with the prodrug ceftobiprole medocaril

Gary Eichenbaum, Jennifer Skibbe, Andrew Parkinson, Mark D. Johnson, Dawn Baumgardner, Brian Ogilvie, Etsuko Usuki, Fred Tonelli, Jeff Holsapple and Anne Schmitt-Hoffmann An approach was...
Scientific Posters

An in vitro test system to evaluate drug-drug interactions with biologics

Authors Maciej Czerwinski1, Christina Renneke2, Joanne Parker2, Chad Pope1, Kevin Lyon1, Catherine Wiegand1, Jason Neat1, Faraz Kazmi1, David Buckley1, and Andrew Parkinson1 1XenoTech, LLC, Lenexa...
Scientific Posters

Temporal changes in CYP3A4 mRNA and activity following treatment of cultured human hepatocytes with interleukin-6 (IL-6): Implications for study design and endpoint selection

In recent years the focus of pharmaceutical drug development (once dominated by small molecule (NCE) therapies) has shifted and is now shared with a significant...
Scientific Posters

Evaluating the potential for lysosomal trapping in immortalized human hepatocytes (Fa2N-4 cells)

Sequestration of high concentrations of lipophilic amines (a.k.a cationic amphiphilic drugs or CADs) in the acidic (pH 4-5) environment of lysosomes contributes to their presystemic clearance.