Protein developability is a critical attribute yet often not evaluated until late in the product pipeline because of challenges in high-throughput characterization. We have developed a platform for library-scale characterization of multiple developability metrics for millions of protein variants and coupled these data with a convolutional neural network to advance understanding of the sequence-developability landscape.

Bringing together advances in sequencing, bioinformatics, automation, and data analysis, we have codified and streamlined selection and characterization of diverse libraries assembled from various antibody discovery platforms. This talk will describe our process for generating extensive manufacturing and physicochemical ‘drug-like properties’ alongside kinetic and cell-based data to rapidly and objectively identify molecules for optimization. The consistency and scale of our operation directly facilitate data science initiatives, which enhances the approach.

Glycoengineering has been incorporated in antibody design to ensure clinical safety and tune the functional activities of antibody drugs. Whereas most glycoengineering approaches target antibody Fc domains, we developed a workflow that introduces atypical glycosylation into antibody Fv domains. We show that this approach can modulate the function and extend the in vivo half-life of antibodies without adversely affecting developability metrics, presenting a general glycoengineering framework for enhancing antibody performance early in the drug development process. 

Characterization of complex Reagent and Therapeutic proteins can be challenging. Here, through multiple vignettes, we will discuss the different mass spectrometry-based strategies that help confirm correct protein expression and identify host-dependant glycan differences, along with modality agonistic high-throughput solutions to analyze large panels of therapeutics.

Characterization of anti-CD20 antibody binding to CD20 is critical to the development of anti-CD20 therapeutics. While SPR is widely used to characterize the binding of therapeutics to their targets, its application to the characterization of anti-CD20 therapeutics has been limited by the challenges of obtaining recombinant or native full-length CD20 suitable for ligand binding assays. We report a novel SPR-based assay enabling elucidation of binding kinetics and affinity for anti-CD20 antibody to EV-expressed CD20.

Emerging markets with low biologic-treatment rates and affordability barriers that impede patients’ access to expensive, innovative medicines present attractive opportunities for biosimilars. Companies can design targeted pricing models for each product and country. Here we discuss how pharma companies can unlock their potential to enter emerging markets, their regulatory pathways, pricing, affordability, and competitive landscapes.

The talk will focus on how we transformed a completely non-HT biologics formulation workflow in the late-stage drug product development into an HT and HT-compatible one in the lab from sample prep to sample analytics. Since the study was designed by JMP, the talk will also demonstrate how we evolved our own mindset to leverage the power of DOE and statistics.

While protein medications are promising for disease treatment, significant challenges persist in delivery of high-concentration formulations. Here, we examine the extensional flow properties with model ovalbumin protein (OVA) and commonly used polysorbate excipients (PS20 and PS80). Despite similarities in structure, pronounced differences in extensional flow behavior are observed for OVA solutions containing PS20 vs PS80. While undesirable elasticity is observed in some high-concentration formulations, polysorbate-containing solutions are more promising than solutions containing higher molecular-weight polymeric excipients. Understanding excipient behavior in extensional flow can help formulate protein medications with greater shelf stability and tolerance to adverse flow effects.

An IgM antibody (IGM-6268) was engineered to specifically target the RBD of SARS-CoV-2 spike protein, with enhanced avidity and potent variant neutralization compared to an IgG antibody. Since administration at the site of infection has the potential for prophylactic and treatment efficacy, IGM-6268 was evaluated for aerosolization targeting the nasal cavity. Development of a stabilizing formulation was paired with Teleflex MAD300 Nasal device delivery characterization, for rapid advancement into clinic.

Cell and gene therapy using viral vectors promises to overcome unmet needs in therapy of severe diseases. These viral vectors provide an analytical challenge during product development and stability assessment as they contain proteins, nucleic acids, and in some cases also a lipid membrane. The talk will provide an overview of latest analytical methods for virus particle characterization and show recent results from, e.g., analytical ultracentrifugation.

Conjugated peptide sequences redefine targeted delivery through their dual nature as both physical and informational constructs. Their physical properties are exploited through their gross electrochemical interactions with cellular structures, most notably the cell membrane. While their informational properties can be harnessed through the cell’s endogenous protein trafficking logic. We will discuss this utility and how to design and characterize their localization of drug actives to and even within organelle targets.