Chimeric heteromultimer adhesins
AssigneeGenentech, Inc.
InventorsVINCENT DANIAL FITZPATRICK, MARK SLIWKOWSKI, RICHARD L. VANDLEN
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Abstract
Novel chimeric heteromultimer adhesins that bind the ligand of natural heteromultimeric receptors and uses therefor are disclosed. The chimeric molecules of the heteromultimer adhesins comprise an extracellular domain of a heteromultimeric receptor monomer and a multimerization domain for the stable interaction of the chimeric molecules in the adhesin. Specifically disclosed are heteromultimeric adhesins comprising the extracellular domains of ErbB2 and ErbB3 or ErbB2 and ErbB4. The chimeric ErbB heteromultimer adhesins of the present invention are useful as competitive antagonists or agonists of a neuregulin for the treatment of diseases such as various cancers.
Claims46
A chimeric heteromultimer adhesin comprising:
- a first amino acid sequence comprising an extracellular domain of a first monomer of a natural heteromultimeric receptor and a multimerization domain;
- an additional amino acid sequence comprising an extracellular domain of an additional monomer of the natural heteromultimeric receptor and a multimerization domain,
- wherein the extracellular domains of the first and additional monomers are associated in a cell to form a natural heteromultimeric receptor which is activated upon binding of a ligand, and
- wherein the chimeric heteromultimer adhesin has 10-1 to 106 fold affinity for the ligand relative to a monomer of the receptor or a homomultimer of the receptor.
Dependencies are inferred from the claim text.