BAARSDNESS, JASON,O'CONNOR-MCCOURT, MAUREEN D.,SULEA, TRAIAN,ZWAAGSTRA, JOHN C.
申请号：
CA2681177
公开号：
CA2681177C
申请日:
2008.03.19
申请国别(地区):
CA
年份:
2019
代理人:
摘要：
The invention provides multivalent ligand binging agents (traps) formembers of the TGF-.beta. superfamily and polypeptide linkers and methods formaking and using such constructs. In an embodiment of the invention there isprovided a multivalent binding agent with affinity for a member of the TGF-.beta.superfamily, said agent comprising the general structure I: (<；bd1 >；-linker1)k-[{<；bd1>；-linker2-<；bd2>；-linker3f} n, -(<；bd3>；)m -(linker4-<；bd4>；)d] h, where: - nand hare independently greater than or equal to 1； - d, f, m and k areindependentlyequal to or greater than zero； -bd1, bd2, bd3 and bd4 are polypeptide bindingdomains having an affinity for the same member of the TGF-.beta. superfamily,withbd1, bd2, bd3, and bd4 being independently the same or different from eachother； and, -linkeri, linker2, linker3 and linker4 are unstructuredpolypeptidesequences； wherein the number of amino acids in each linker is determinedindependently and is greater than or equal to X/2.5； where, X equals theshortestlinear distance between: (a) the C-terminus of an isolated form of the bindingdomain that is located at the N- terminus of the linker and that isspecificallybound to its ligand； and, (b) the N-terminus of an isolated form of thebindingdomain that is located at the C-terminus of the linker and that isspecificallybound to its ligand.
