Emerging Therapeutics

eBook: MSC-Derived Extracellular Vesicles Challenges in Production, Scale-Up, and Characterization

The discovery of extracellular vesicles (EVs) as an intercellular communication medium has led to explorations of their therapeutic potential. EVs constitute a heterogeneous mixture of several different vesicle populations that may be similar in size but different in content, or vice versa. The vesicles can contain RNAs and proteins as well as DNAs and lipids as biological cargoes. Those cargoes can exist either intraluminally within EVs or on their surface, adding complexity to analytical considerations. EVs are classified into subpopulations…

BioProcess Insider Interview: Brian Finrow, Lumen Biosciences

Moderator: Dan Stanton, Co-founder and Editor, BioProcess Insider. Featuring: Brian Finrow, Co-founder & CEO, Lumen Biosciences. Although Chinese hamster ovary (CHO) cells remain the biopharmaceutical industry’s preferred expression system for antibody production, companies such as Lumen Biosciences are seeking out alternative hosts. Finrow cautioned that CHO cells sometimes complicate efforts to develop scalable and cost-effective manufacturing processes. For gastrointestinal (GI) indications such as Clostridium difficile infection and Crohn’s disease, spirulina, a biomass composed of cyanobacteria and their cellular by-products, could…

Delivering on the Promise of Bispecifics: State-of-the-Art Bispecific Antibody Development

Bispecific antibodies (bsAbs) have transformed the field of immunotherapy. However, moving these life-changing therapeutics from the bench to the clinic can be time-consuming and costly. Further, challenges such as aggregation, degradation, fragmentation, and denaturation may ultimately hinder a program from advancing to the clinic. Partnering with a CDMO with relevant experience and technologies can be critical for safely and cost-effectively manufacturing bispecific antibodies. With Selexis’s cell line technology and KBI Biopharma’s manufacturing and analytics, we lead the industry in technologies…

Increasing Dynamic Binding Capacity of Oligo(dT) for mRNA Purification: Experimental Results Using CIM 96-Well Plates

Messenger RNA (mRNA) emerged as a powerful therapeutic tool for treatments in gene therapy, oncology, and infectious diseases, as recently demonstrated by vaccines against Covid-19. mRNA is produced by an enzymatic reaction that can be rapidly designed and scaled-up, and the platform is highly adaptable to different targets. One of the greatest challenges in mRNA production is the removal of process-related impurities stemming from in vitro transcription (IVT) reaction, such as residual nucleotide triphosphates, DNA template, enzymes, abortive transcripts. Affinity-based…

Managing Manufacturing Requirements for Live Biotherapeutics

In 2018, Synlogic explored options for producing clinical-trial material for its lead programs, including a candidate therapy for the rare metabolic disease phenylketonuria (PKU). Like other emerging drug developers, the company evaluated the merits of outsourcing manufacturing to third parties. However, Synlogic leverages synthetic biology tools to design and develop therapeutics based on genetically engineered microbes. Thus, it also needed to consider requirements specific to live biotherapeutics. Late in 2018, Synlogic announced plans to establish its own current good manufacturing…

Pseudomonas fluorescens: Cell-Line Development of a Commercially Proven Platform for Biopharmaceutical Manufacturing

A number of factors contribute to delivering a robust, highly productive, and reliable process for manufacturing a therapeutic protein. They begin with a cell-host system and a gene-expression strategy that determine a developer’s ability to optimize growth and expression titers. But for many therapeutic proteins, initial attempts to develop a production process are based on evaluation of limited factors and tend to yield only small quantities or poor product quality. Automation can enable parallel building and expression screening of diverse…

The Evolution of Predictive Toxicology: Improving Predictivity Using New-Approach Methodologies

A pharmaceutical’s approval for commercial distribution is contingent on submission of pharmacological and toxicological safety data as defined by regulatory agencies such as the US FDA and ICH. Guidances state that such data can come from in vivo or in vitro studies. The current paradigm works well for collecting critical data about, e.g., a drug’s pharmacological effects and mechanism of action (MoA). However, increasing evidence points to current methods’ inadequacy for predicting a drug’s risks to human patients. Such limitations…

The CRISPR Saga (So Far)

Since January 2016 (with a brief interlude as described below), the Patent Trial and Appeal Board has been attempting to adjudicate the proper inventorship of CRISPR technology in (to date) six separate patent-interference proceedings. (Scientific “priority has been decided, for now, by the awarding of the Nobel Prize in Chemistry to Jennifer Doudna and Emmanuelle Charpentier in 2020; see the “Priority Claims” box). CRISPR-based gene editing was hailed as the “Breakthrough of the Year” in 2015 (1), and the scientific…

Antibody-Derivative Biotherapeutics: Fragments and Fusions Define the Future

Monoclonal antibodies (MAbs) remain the dominant biopharmaceutical product class, but as biotechnologies have advanced in recent decades, developers have found ways to exploit their “magic-bullet” capabilities while putting aside their limitations. That has led to a new generation of antibody-related therapeutics created by cutting and pasting molecular domains. Researchers are mixing and matching functional moieties of antibodies and other molecules to create custom-designed proteins with powerful efficacy and tunable targeting. A simple search at Taylor & Francis Online (https://www.tandfonline.com), the…

Development and Manufacture of Therapeutic Bispecific Antibodies

To meet the ongoing need for new and improved drugs, the biopharmaceutical community strives to create molecules with new functions. Bispecific antibodies (bsAbs), which can simultaneously home in on two different targets, illustrate the scientific ingenuity needed for this task. The basic proof of concept for these complex molecules was established in 1960 (1), and their application to the redirection of effector cells was reported in the mid-1980s (2–4), but producing them has proved to be challenging. Many technical advances,…