XpressCF™ and XpressCF+™

Our Scalable Biochemical Protein Synthesis Platform: Designing and Manufacturing a New Generation of Biotherapeutics

Conventional methods for expressing proteins utilize cell lines originating from bacteria, yeast, insects, plants, or mammals. Because these methods require intact, functioning cells, the biochemical and biophysical parameters under which proteins are produced using these methods are inherently limited, often failing to produce many proteins and biologics. Using cell-based expression systems to produce protein variants is also a cumbersome way to enable selection of the best therapeutic candidates.

Our technology is different. Sutro’s technology platform is made possible by the separation, into an extract, of the cellular components required to produce proteins from the process of protein generation itself. The extract includes all the necessary biochemical components for energy production, transcription and translation and can be used to support cell-free biochemical protein synthesis by the addition of the specific DNA sequence for the desired protein. The process produces single proteins at g/L yields in 8-10 hours at any scale.

Sutro designs, discovers, characterizes, and manufactures therapeutic proteins for the treatment or prevention of diseases for itself and for its partners using its proprietary XpressCF™ and XpressCF+™ platform technologies. Our XpressCF™ technology allows us to provide customized manufacture, design and development of therapeutic proteins and to discover drugs that feature therapeutic proteins that contain only amino acids all for the treatment and prevention of diseases. XpressCF+™ is used to design, discover, characterize, and manufacture therapeutic proteins that contain one or more non-natural amino acids in addition to natural amino acids and to discover drugs that feature such proteins.

In addition, Sutro uses ProteinSAR™ to conduct research to identify and characterize the structure, function and the relationship of the therapeutic proteins. Sutro’s advanced technology allows a rapid and deep analysis of structure-function relationship that is not practical with traditional cell-based methods for protein expression.

A wide variety of protein products have been produced using Sutro’s platform. These range from small peptides to multimeric complex mammalian proteins such as monoclonal antibodies.Uniquely, production of proteins in our cell free system can be scaled rapidly from sub-1mL scale to manufacturing scale; the platform is effectively a liquid handling solution to protein synthesis. The advantages of such a flexible platform over conventional cell-based expression systems are enormous:

  • Proteins can be rapidly engineered and optimized by producing many variants in parallel in 96-well plates from DNA libraries
  • Producing large quantities of a particular protein can be accomplished days from first DNA synthesis, allowing large animal pharmacology and safety assessments to be performed during the design and discovery phase of development
  • Linearly scalable candidate production is assured with predictable performance from bench to GMP production
  • A single master cell bank used for extract generation is capable of providing the manufacturing format for many different proteins, leading to accelerated development times
  • Extract stockpiling provides a means for flexible and fast deployment of surge protein production in the event of unexpected demand for product
  • The synthesis of many novel therapeutic proteins and families of proteins that are challenging by cell-based expression systems is now feasible, for example: Difficult-to-fold proteins, Cytotoxic molecules, and Non-natural amino-acid containing proteins

 

Technology Summary

 

XpressCF™

Using XpressCF™, Sutro designs, discovers, characterizes, and manufactures therapeutic proteins for the treatment or prevention of diseases for itself and for its partners.  XpressCF™ allows us to provide customized manufacture, design and development of therapeutic proteins and to discover drugs that feature therapeutic proteins that contain the 20 natural amino acids.  One of the principle advantages of XpressCF™ is that it enables extremely rapid make-test cycles and does not require any cell line development for the scaling of production of proteins.

 

XpressCF+™

Using XpressCF+™, Sutro designs, discovers, characterizes, and manufactures therapeutic proteins for the treatment or prevention of diseases for itself and for its partners.  XpressCF+™ allows us to provide customized manufacture, design and development of therapeutic proteins and to discover drugs that feature therapeutic proteins that contain an unnatural amino acid in addition to the 20 natural amino acids.  Using XpressCF+™ to incorporate an unnatural amino acid results in a protein that can be conjugated to a chemical of interest in a site specific manner, enabling homogenous single-species protein-drug conjugates.