Unmet Need: Methods to control glycosylation, a critical post-translational modification of therapeutic proteins, now focus on maintaining conventional glycosylation profiles. Strict adherence to naturally-occurring glycosylation patterns, however, hinders and in some cases precludes the development of novel protein therapeutics required for rare diseases or the optimization and improvement of biologics used diagnostically or therapeutically for prevalent disorders such as cancer. There is thus a critical need to develop innovative methodologies to rationally and precisely engineer the glycosylation profiles of protein drugs to create new therapeutics, improve their pharmacologic properties, and facilitate manufacturing.
Technical Details: Researchers at Johns Hopkins University have developed an integrated technology platform to glycoengineer protein-based drugs to improve therapeutic properties, manufacturability, and efficacy. This comprehensive platform can introduce N-linked glycosylation sites into protein drug candidates, generate engineered drug variants with bespoke glycosylation patterns using genetically modified cell lines, and enhance production using proprietary hexosamine analogues that increase the overall consistency and efficacy of glycosylation-modified drug candidates. Central to this process, the platform utilizes a cell line that is responsible for the majority of therapeutic protein production, including virtually all therapeutic antibodies; these cells are genetically modified to improve N-glycan branching, sialylation, and additional aspects of glycan biosynthesis for precise regulation of glycosylation. This system has been demonstrated for the production of bioengineered antibodies and for enzyme replacement therapy with optimized safety, stability, yield, and pharmacokinetic and pharmacological properties. In addition, this platform can be used in conjunction with hexosamine analogue supplementation to install orthogonal chemical functional groups for applications such as antibody-drug conjugate formulation. Overall, this versatile platform allows for custom-designed and optimized glycosylation of proteins and provides flexibility in the design of bioengineered protein therapeutics.
Value Proposition:
· Novel site-specific conjugation methodology to produce glycoengineered protein therapeutics with enhanced pharmacologic properties
· Platform facilitates design of protein therapeutics with improved safety, stability, yield, and efficacy
Looking for Partners to: Develop & commercialize the technology as a methodology and production platform to glycoengineer all classes of therapeutic proteins for improved properties.
Stage of Development: Pre-Clinical
Data Availability: In vitro and in vivo proof of concept
Inventors: Kevin Yarema, Christian Agatemor, Christopher Saeui, Matthew Buettner, Jamie Spangler, Seth Ludwig
Patent Status: Pending
Associated Technology: C12708
