Method of targeting a therapeutic agent to cells expressing the erb B-3 receptor

US5820859A · kind A · utility

Assignee

• The United States of America, as represented by the Department of Health and Human Services · US

Inventors

• Matthias H. Kraus · Bethesda, US
• Stuart A. Aaronson · Great Falls, US

Key dates

• Filing date: Jun 7, 1995
• Grant date: Oct 13, 1998
• Expiry date: Jun 7, 2015

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2500/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro. Ligand-dependent signaling of its cytoplasmic domain was established employing transfectants which express a chimeric EGFR/erbB-3 protein, gp180.sup.EGFR/erbB-3. EGF induced tyrosine phosphorylation o…