Novel bifunctional multispecific antagonists capable of inhibiting more than one ligand in TGF-beta family and uses thereof

• Main Authors: HAN HUIQUAN, ZHOU XIAOLAN
• Format: Patent
• Language: Chinese; English
• Published: 22.09.2023
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

The present disclosure describes novel polypeptide antagonists capable of neutralizing more than one member of the TGF-beta family in a selective manner. In particular, the multispecific polypeptide antagonists disclosed herein comprise at least one activator-binding domain and at least one TGF-[beta]-binding domain, and thus are capable of neutralizing TGF-[beta] and activator proteins as well as activator-related ligands in parallel. In addition, the present disclosure also discloses bifunctional multispecific polypeptide antagonists designed to inhibit activator proteins, TGF-beta, and T cell immune checkpoints (i.e., PD1, PDL1, or CTLA4) in a simultaneous manner. In particular, the bifunctional multispecific antagonists disclosed herein comprise at least one activator binding domain, at least one TGF-beta binding domain, and at least one PD1 binding, PDL1 binding, or CTLA4 binding domain. Also provided are pharmaceutical compositions of such multispecific or bifunctional multispecific polypeptide antagoni