This includes the flexible genetic fusion of unique Precision Targeting moieties with certain carrier domains, readily creating “targeted carrier” proteins. These carriers carry precisely defined payloads, similar as Antibody Drug Conjugates, yet benefit from a much more straightforward, cheaper and quicker development process. Readily adjustable in-vivo half-lives of such Precision Targeting Affilin®-carriers allow easy adjustment to individual therapeutic and/or diagnostic needs.
Starting point is a scaffold protein with favorable characteristics such as:
• small size (<10kDa)
• very high thermal, proteolytic and caustic stability
• no post-translational modifications
• no cysteines
• cost effective production in E.coli
High quality and diverse libraries are generated from the starting scaffold by randomization of a number of surface-exposed residues at the genetic level. Each randomized position now comprises all amino acids (except Cysteine) which leads to large combinatorial libraries with complexities of 1010 to 1012, depending on the specific display format used.
Selection and Screening
For the subsequent selection process, both phage display and ribosome display are available. The following automated, robotics-assisted high-throughput screening (HTS) key technology identifies Precision Targeting ligand-enriched selection pools. Further rigorous screening rounds finally yield those Precision Targeting ligands or Precision Radio Conjugates with the desired properties and suitable for large-scale industrial use.
As foundation for all this, Navigo Proteins has tailored an HTS platform optimized for flexible assay design and selection based on multiple parameters. Rapid screening of well beyond 10.000 Affilin® binders per day identifies a set of diverse Precision Targeting candidates from which we select the most promising leads for further development.
The development of innovative biotherapeutic or diagnostic protein molecules is often based on their chemical or genetic modification to modulate or extend their functionality. Examples are multi-specific binding molecules, e.g. fusions of Precision Targeting binders with antibodies or Fab fragments. Innovative fusion proteins for instance are created by connecting Precision Targeting molecules with certain carrier domains, to introduce a precise number of functional/coupling/binding sites at defined positions to the carrier. The adjustable size of the carrier then determines a custom-tailored in vivo half-life. The functional spectrum is further broadened by introduced specific chemical modifications, such as coupling of chelators for radio nucleotides. Our scientists at Navigo Proteins apply their expert know-how to design the optimal molecule format for every specific task.
An in-depth functional characterization of the lead ligands along the development process is crucial to identify the optimal Precision Targeting Ligands. The characterization comprises a range of biochemical, biophysical as well as functional protein assays in house, such as cell-based assays, flow cytometry or immune histochemistry, to meticulously select the optimal Precision Targeting Affilin® molecules.
Navigo Proteins pursues a stringent policy of patenting its proprietary products and technology. Over 100 patents are granted and dozens of applications have been filed. This is the basis to secure our assets in all major markets and provides customers with a solid protection and exclusivity of the licensed products and technology.