On 10 December 2020, BPI presented an “Ask the Expert†webinar with Jason Sterling, PhD (principal scientist and project director in analytical and formulation resources), and John Rockwell (group leader) of Catalent Pharma Solutions. Biophysical characterization is critical to understanding the makeup and behaviors of biologic therapies and vaccines both early in development and throughout scale-up for manufacturing. As biologics become more complex in structure and as scientists improve their understanding of the effects of structure on stability, efficacy, and…
Emerging Therapeutics
Exciting Starts for New Players and Platforms: Nucleic-Acid Vaccines Prepare for Their Commercial Debut
Although vaccine platforms based on messenger RNA (mRNA) are enjoying the limelight in the wake of emergency authorizations of products from Pfizer–BioNTech and Moderna, DNA vaccines are poised to make their own commercial debuts soon. The World Health Organization (WHO) reports that six of the 48 candidate vaccines against SARS-CoV-2 that remain in clinical trials are DNA-based products, as are 14 others in preclinical study (1). I spoke with Hong Jiang (cofounder and chief operating officer of Aegis Life, Inc.)…
Removing Oligomers of a Recombinant Human Therapeutic Hormone:
Evaluation of Chromatographic Options for Effectiveness
Aggregation is a common cause of protein instability, which renders a biologic product unfit for therapeutic use. Sometimes it is difficult to purify monomeric proteins from oligomers because of similarities in their isoelectric points (pIs). Proteins such as hormones have pI ranges similar to their oligomers and thus can be difficult to separate out using a conventional polishing chromatographic step such as ion exchange. With those pI similarities, removal of oligomers to a considerable extent by ion exchangers can compromise…
A Universal Assay Determination Method for Antisense Oligonucleotides: A New Slope Spectroscopy Method
Antisense oligonucleotides (ASOs) are short, synthetic, single-stranded oligodeoxynucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms. ASO technology has become an important drug discovery platform for most major pharmaceutical companies. To date, six antisense drugs have been approved by regulatory agencies to treat diseases spanning viral infections, hyperlipidemias, and neurological diseases. More than 50 additional ASO drugs are in clinical trials. For an ASO drug product, an assay of its active pharmaceutical ingredient…
eBook: Biomarkers — Improving Clinical Studies to Enhance Commercial Success for Biologics
The biopharmaceutical industry continues to invest heavily in technologies for identification of predictive biomarkers. Drug developers want not only to find quantitative evidence that their therapies will work as designed, but also to anticipate which patient populations will respond positively to those regimens. Doing that could streamline clinical trials, accelerate approvals, and ultimately improve patient outcomes. Advances in next-generation sequencing and increases in computational capability now are facilitating biomarker inquiries, especially in the realm of immunooncology. However, predictive biomarkers remain…
Making Safe and Effective CAR T Cells: How Droplet Digital PCR Can Improve Their Quality Control
Chimeric antigen receptor (CAR) T cells first entered US clinics in 2017 (1), and this therapeutic modality holds tremendous potential as one of the most effective forms of personalized cancer care ever to reach patients. The revolutionary impact of CAR T-cell therapy comes from its ability to rewire our own immune defenses to kill cancer cells: It essentially modifies a patient’s naturally existing immune cells to boost their recognition and attack of cancer cells so that the person’s own immune system…
G-Protein–Coupled Receptors: Promising Targets for Antibody–Drug Conjugates
G-protein–coupled receptors (GPCRs) are a large and diverse family of seven-transmembrane–domain proteins expressed on the surface of human cells. These molecules respond to external stimuli by initiating signal-transduction pathways that affect the expression of a large family of genes — which, in turn, regulate a range of vital physiological processes and functions. Figure 1 illustrates the general pathways of GPCRs. Without these proteins, humans simply could not survive: Without β-adrenergic receptors, we could not regulate our blood sugar, for example;…
eBook: Antibody–Drug Conjugates — Refining Product Designs for Improved Outcomes
Antibody–drug conjugates (ADCs) seek to partner the target specificity of antibodies with the cell-killing punch of chemotherapy drugs. Researchers identify antibodies that bind to proteins found predominantly or exclusively on the surfaces of cancer cells. The cells can absorb the ADC into their interiors, where the chemical environment or enzymes detach the drug from the antibody, freeing it to wreak havoc. Although nine ADCs have received US Food and Drug Administration (FDA) or European Medicines Agency (EMA) approval (and many…
eBook: Cancer Vaccines â — Innovation Fuels an Immunotherapy Renaissance
Despite early successes a decade ago, cancer vaccines designed to deliver peptides or proteins — or nucleic acids encoding those antigens — generally have fizzled out since then. As a result, cancer vaccine development and the field of immunotherapy lost some traction overall. But as freelance contributor Jim Kling describes in this eBook, new innovations in product design, testing, and manufacturing are fueling a renaissance in cancer vaccine development. From checkpoint inhibitors to neoantigens, immune regulators, and beyond, companies are…
eBook: A Light-Chain Platform for Developing Bispecific Antibodies
Biopharmaceutical researchers are focusing on novel platforms to quickly develop bispecific antibody (BsAb) therapies for treating complex diseases such as cancer. BsAb therapies offer several advantages because they are designed to bind two unique epitopes. In this report, Bill Lundberg, president and chief executive officer at Merus, describes his company’s efficient approach to developing BsAbs using “common light chain†technology and other proprietary strategies. Lundberg also addresses the company’s approach to typical BsAb development and manufacturing challenges. Fill out the…