TGFB TYPE II-TYPE III RECEPTOR FUSIONS

摘要

Certain embodiments are directed to novel heterotrimeric fusions in which the ectodomain of the TGF-β type II receptor (TβP?II) is coupled to the N- and C-terminal ends of the endoglin-domain of the TGF-β type III receptor (TpRIIIE). Certain embodiments are directed to novel heterotrimeric polypeptides in which the ectodomain of the TGF-β type II receptor (TI3RII) is coupled to the N- and C-terminal ends of the endoglin-domain (E domain) of the TGF-β type III receptor (TI3RIII). This trimeric receptor, known as RER, can bind all three TGF-β isoforms with sub-nanomolar affinity and is effective at neutralizing signaling induced by all three TGF-β isoforms, but not other ligands of the TGF-β superfamily, such as activins, growth and differentiation factors (GDFs), and bone morphonogenetic proteins (BMPs).

主权项

1. A heterotrimeric fusion protein comprising:
(a) an amino terminal segment comprising a first TGFβ binding domain of TGFβ receptor type II, (b) a central segment comprising a endoglin-domain of TGFβ receptor type III, and (c) a carboxy terminal segment comprising a second TGFβ binding domain of TGFβ receptor type II.