OLIGOMERS FOR TNF SUPERFAMILY INHIBITION, METHODS OF MAKING AND USING

摘要

Methods for constructing efficient inhibitors of target TNF superfamily receptors, single chain target TNF superfamily ligands that inhibit of target TNF superfamily receptors while failing to engage or inhibit non-target TNF superfamily receptors, and methods of their use to treat diseases are provided. Single chain RANKL, TNF, and TRAIL ligands that effectively inhibit their target receptors while failing to inhibit non-target TNF superfamily receptors are also provided.

主权项

1. A method for constructing an inhibitor of a Tumor Necrosis Factor superfamily (TNFsf) member receptor comprising the step of combining in a single polypeptide chain:
(i) at least one first mutated TNFsf monomer that comprises at least one first mutation that blocks binding of a TNFsf member comprising the first mutated monomer to its corresponding target Tumor Necrosis Factor superfamily receptor; and (ii) at least one second mutated TNFsf monomer that comprises at least one second mutation that increases binding affinity of a TNFsf member comprising the second mutated monomer to the corresponding target Tumor Necrosis Factor superfamily receptor,wherein at least three mutated TNFsf monomers are combined in the single polypeptide chain.