ErbB4 antagonists
OwnerMary E. Gerritsen, Mark X. Sliwkowskiinventors
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Abstract
The present invention concerns methods and means for controlling excessive proliferation and/or migration of smooth muscle cells, and in particular for treating stenosis, by using antagonists of a native ErbB4 receptor. The invention further concerns a method for the identification of ErbB4 agonists and antagonists capable of inhibiting or enhancing the proliferation or migration of smooth muscle cells.
Claims84
A method for controlling excessive proliferation or migration of smooth muscle cells comprising treating said smooth muscle cells with an effective amount of an antagonist of a native ErbB4 receptor.
A method for treating stenosis in a mammalian patient comprising administering to said patient an effective amount of an antagonist of a native mammalian ErbB4 receptor.
A method for treating stenosis in a mammalian patient comprising introducing into a cell of said patient a nucleic acid encoding an antagonist of an ErbB4 receptor.
A method for treating hypertension associated with vascular stenosis in a mammalian patient, comprising administering to said patient an effective amount of an antagonist of a native mammalian ErbB4 receptor.
A pharmaceutical composition for the treatment of stenosis in a mammalian patient comprising an effective amount of an antagonist of a native mammalian ErbB4 receptor, in admixture with a pharmaceutically acceptable carrier.
A method for identifying a molecule that inhibits or enhances the proliferation or migration of smooth muscle cells, comprising the steps of:
- (a) contacting a polypeptide comprising an amino acid sequence having at least 85% sequence identity with the amino acid sequence of the extracellular domain of a native ErbB4 receptor and retaining the ability to control excessive proliferation or migration of smooth muscle cells, with a candidate molecule;
- and
- (b) determining whether the candidate molecule inhibits or enhances the ability of said polypeptide to control excessive proliferation or migration of smooth muscle cells.
An antibody that binds essentially the same epitope of ErbB4 as an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession Number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825).
An antibody that has complementarity determining region (CDR) residues from an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825).
An antibody selected from the group consisting of an antibody produced by a hybridoma selected from the group consisting of HER4.10H1.1A1 (ATCC Accession Number PTA-2828), HER4.1C6.A11 (ATCC Accession Number PTA-2829), HER4.3B9.2C9 (ATCC Accession Number PTA-2826), HER4.1A6.5B3 (ATCC Accession Number PTA-2827) and HER4.8B1.2H2 (ATCC Accession Number PTA-2825).
An antibody that binds essentially the same epitope of ErbB4 bound by an antibody selected from the group consisting of anti-ErbB4 monoclonal antibodies 4-1440, 4-1460, 4-1473, 4-1492 and 4-1464.
An antibody that has complementarity determining region (CDR) residues from an antibody selected from the group consisting of anti-ErbB4 monoclonal antibodies 4-1440, 4-1460, 4-1473, 4-1492 and 4-1464.
An antibody which binds to ErbB4 with high affinity.
An antibody which is capable of binding to both ErbB4 and ErbB3.
An antibody which binds to ErbB4 and reduces heregulin binding thereto.
An antibody which binds to ErbB4 and reduces heregulin-induced tyrosine phosphorylation thereof.
Dependencies are inferred from the claim text.