XTEN Concept

XTEN protein polymers combine features of both chemical polymers and globular proteins

XTEN technology brings the precision of recombinant protein biosynthesis to polymer chemistry. XTEN protein polymers, similar to chemical polymers, have undefined structure (random coil) and use a limited number of monomers, while utilizing recombinant protein expression to achieve defined length and sequence. 


XTENylation of therapeutic payloads can be achieved by both recombinant fusion and chemical conjugation 

XTEN can be recombinantly fused to therapeutic proteins to increase their in vivo half-life. Recombinant fusion allows attaching multiple XTEN chains per protein in precisely-defined locations resulting in best-in-class pharmacokinetics as exemplified by XTENylated growth hormone (somavaratan, Versartis) and FVIII-XTEN (with Bioverativ (spinout of Biogen)).

XTEN protein polymers can be produced as intermediates for chemical conjugation to peptides, peptidomimetics, and other drug molecules. Reactive groups (thiol, amine) are inserted in precisely-defined positions along the polypeptide via introduction of cysteine or lysine codons into XTEN-encoding genes. Orthogonal conjugation to amino and thiol groups in XTEN facilitates the production of bi-functional molecules.


XTEN technology offers exceptional homogeneity and monodispersity 

XTEN protein polymers are produced by high-yield microbial expression and purified by industry standard scalable chromatographic methods.

XTEN protein polymers lack secondary and tertiary structure and their solution behavior resembles chemically prepared polymers with very large hydrodynamic radii. By size exclusion chromatography (SEC), XTEN protein polymers appear much larger than typical globular proteins of similar molecular weight. The bulking effect of XTEN greatly reduces renal clearance of attached molecules, thus increasing their in vivo half-lives. The length of XTEN protein polymers can be customized to optimize the pharmacokinetics as well as the bio-distribution of attached payloads.

XTEN protein polymers are homogeneous by denaturing polyacrylamide electrophoresis (SDS-PAGE) and monodisperse by electrospray ionization mass spectrometry (ESI-MS) as compared to heterogeneous chemical polymers such as polyethylene glycol (PEG).

Highly hydrophilic XTENs are compatible with both analytical and preparative reverse phase (RP) chromatography. As a result, XTENylated peptides and proteins can be routinely purified and analyzed by C4 or C18 RP-HPLC.