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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.

 

Publications

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2020 FDA Draft Guidance, “Drug-Drug Interaction Assessment for Therapeutic Proteins Guidance for Industry”

In August 2020, the FDA released the draft guidance for industry to evaluate therapeutic proteins for drug-drug interaction (DDI) potential using a risk-based approach.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

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. Based on the publication: Kazmi F, Yerino P, McCoy...
Blog

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...

Webinars

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 Paul Tarantino1, Tim Sullivan1, Brian Ogilvie2, Maciej Czerwiński2 1 Idera Pharmaceuticals, Inc.,...
Blog

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,...
Blog

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...

Publications

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...
Blog

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...

Publications

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...
Publications

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...
Blog

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...
Webinars

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

Direct and Cytokine-Mediated Effects of Albumin-FusedHuman Growth Hormone, TV-1106, on CYP Enzyme Expression in Human Hepatocytes In Vitro Drug-drug interactions involving therapeutic proteins that can...
Publications

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...
Publications

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

Inflammation, infection, vaccination, and some marketed therapeutic proteins (biologics) are associated with cytokine-mediated suppression (down-regulation) of drug-metabolizing enzymes (DME). Biologics, such as monoclonal antibodies, can trigger...
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

Temporal changes in CYP3A4 mRNA and activity following treatment of culturedHuman hepatocytes with interleukin-6 (IL-6): Implications for study design and endpoint selection In recent years...
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.