Emerging Therapeutics

Apparent Matrix Effects in an Iduronate 2-Sulfatase Specific Activity Assay

The recombinant fusion protein SHP631 consists of a chimeric monoclonal antibody binding to human insulin receptor and iduronate-2-sulfatase (I2S). This product is being developed as an enzyme replacement therapy to treat cognitive symptoms of Hunter’s syndrome. Because the current therapy (idursulfase, brand name Elaprase from Shire) cannot cross the blood–brain barrier (BBB), SHP631 is being developed to do so, enabling the presence of I2S in the brain. The enzymatic activity of this molecule is measured using the substrate 4-methyl umbelliferyl-α-L-idopyranosiduronic…

Partnerships in Immunotherapy for the Future of Cancer Treatment

Immunotherapy seeks to harness the power of our human immune system to fight disease. In this rapidly evolving field, collaboration among different stakeholders is essential to bringing new treatments to market. Patient advocacy groups, researchers, hospitals, manufacturers, and government entities all are working together to translate promising new research into life-saving products. Types of immunotherapy include monoclonal antibodies (MAbs) and antibody derivatives, checkpoint inhibitors (immune-modulating proteins), cancer vaccines, T-cell therapies, and cytokines — so the approach involves a range of…

A Brief History of Adherent Cell Culture: Where We Come From and Where We Should Go

In the past 20 years, novel therapeutics have become a major segment of biopharmaceutical research and development, particularly for immune disorders and cancer. Progress in gene therapies could bring cures for once deadly and debilitating genetic disorders such as hemophilia or muscular dystrophy. Biologic drug products offer potential treatments that have not been possible with traditional (chemistry-based) approaches. But such products also are more difficult to produce cost effectively at an industrial scale because of the intricacies associated with biological…

Messenger RNA Drugs: Engaging the Machinery of Patients’ Cells to Therapeutic Effect

Although most of the bioprocess industry has focused on process development for large-molecule formulations (e.g., protein drugs), a growing segment of the industry has been concentrated on other types of biotherapeutics to leverage advances in understanding of immunology and genetic engineering. Such technologies may emerge both as tools for drug manufacturing and at some point, as biopharmaceuticals, biotherapeutics, vaccines, and cell and gene therapies,  themselves. What brings mRNA research to BioProcess International’s attention is the increasing interest turned toward therapeutic…

Development and Biomanufacturing Strategies for Next-Generation Antibody-Drug Conjugates

The development and manufacture of antibody-drug conjugates (ADCs) requires a series of complex steps. ADC manufacturers must comply with guidelines for both the small-molecule linker-drug and the monoclonal antibody (MAb). The authors describe their company’s development of its lead ADC product. They review process decisions, including the issues that factored into their selection of single-use systems, manufacturing challenges (differences between ADCs and MAbs), and testing methodologies for extractables and leachables. Synthon began as a small-molecule generics company in 1991. During…

Rolling with the ‘Tides: Elucidating the Role of Peptides and Oligonucleotides in the Biopharmaceutical Industry

In earlier issues of BPI we published a few “Elucidation” closers that we called “Defining Moments.” Since then, we have tried to distinguish key confusable terms from one another. Those presented (and sometimes “elucidated”) have been analytical and bioanalytical, spectroscopy and spectrometry, and biosimilars and biobetters. They are just a few of the many confusable terms in the biopharmaceutical industry. For example, when someone says “drug delivery,” a formulator will think of a syringe or transdermal patch, but a logistics…

Partnerships in Immunotherapy: Working Together to Take Cancer Treatment to the Next Level

Biopharmaceuticals are a particularly complex expression of medicine — and immunotherapies perhaps even more so. As treatments, these products themselves often also need “partners” of a kind: e.g., radiation/radiotherapies, traditional MAbs, and chemotherapies. Just as this field of endeavor requires the input and expertise of many different disciplines — from medical researchers to process engineers, clinicians to business leaders, and market experts to policy makers — this discussion of the topic of partnerships in immunotherapy brings together different experts in…

Biological Stealth Bombers: Potency, Regulatory, and Bioprocessing Concerns of Antibody–Drug Conjugates

Seven years ago, the US Food and Drug Administration (FDA) approved the first product in a new class of biologics: antibody–drug conjugates (ADCs). The idea for these products already had been hatched a decade earlier when the promising field of antibody research — touting such molecules as “magic bullets” — had faltered, specifically against oncology-related indications. The early crop of anticancer monoclonal antibodies (MAbs) proved to have only limited efficacy, and interest in developing antibodies as therapeutic agents against cancer…

Process Analytics and Intermediate Purification of Bispecific Antibodies with a Non-Affinity Platform

The therapeutic benefits of monoclonal antibodies (MAbs) have been demonstrated in recent decades with uncontestable success as treatments for human disease. Despite MAbs’ key features such as specificity, selectivity, and safety, the format has limitations (1, 2). Bispecific antibodies may overcome number of difficulties (3). Multiple formats of bispecific antibodies have been developed, although only the κλ-body is fully human and devoid of linkers or mutations. It requires no genetic modifications of heavy and light chains and results in bispecific antibodies…

Therapeutic Modalities: Business and Manufacturing Strategies Influencing Decisions to Develop One Therapy Type Rather Than Another

Moderator Patricia Seymour, with John Lee, Michael Kaufman, Jennifer Michaelson, and Weichang Zhou Following introductions of the panelists and their companies’ technologies, moderator Patricia Seymour began the discussion about challenges related to choosing different modalities and addressing related manufacturing concerns. Targeting Modalities Michaelson began by describing how Cullinan Oncology selects its targets and modalities, how it approaches those early phase decisions, and what its primary driver is to get into the clinic as quickly as possible. She talked about challenges…