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AssigneeGenentech, Inc.
InventorsBrian C. Cunningham, Abraham M. DeVos, Michael G. Mulkerrin, Mark Ultsch, James A. Wells
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We have discovered that growth hormones form ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.
A method for determining whether a candidate ligand that binds to a first receptor polypeptide antagonizes a native, monomeric ligand having four amphipathic alpha helices, wherein said native ligand forms ternary complexes with said first receptor polypeptide and a second receptor polypeptide, said method comprising:
A method for determining whether a candidate ligand that binds to a first receptor polypeptide potentially has agonist activity corresponding to a native, monomeric ligand having four amphipathic alpha helices, wherein said native ligand forms ternary complexes with a first receptor polypeptide and a second receptor polypeptide, said method comprising:
A method for determining whether a candidate ligand that binds to a first receptor polypeptide has agonist activity corresponding to a native ligand selected from the group consisting of growth hormone, prolactin, and placental lactogen, wherein said native ligand forms ternary complexes with a first receptor polypeptide and a second receptor polypeptide, said method comprising:
Dependencies are inferred from the claim text.