Fusion proteins that include antibody and nonantibody portions

US6403769B1 · kind B1 · utility

Assignee

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

Inventors

• William LaRochelle · Madison, US
• Stuart A. Aaronson · Great Falls, US
• Olaf Dirsch · Bethesda, US

Key dates

• Filing date: Feb 22, 1996
• Grant date: Jun 11, 2002
• Expiry date: Feb 22, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The high affinity which is characteristic of homodimers of IgG heavy chains is achieved, along with favorable secretion and flexibility/adaptability properties, in a fusion protein that has a nonantibody portion, comprised of an effector domain, joined to the aminoterminal end of an IgG-derived sequence consisting of a hinge:CH2:CH3 segment which lacks a CH1 domain, with a heterologous signal peptide preferably provided upstream of the nonantibody portion. Chimeric molecules of this structure can be secreted readily in stable form by mammalian cells transfected with DNA encoding the molecule, and are amenable to rapid, efficient purification to homogeneity, for example, using protein A. These molecules are effective substitutes for monoclonal antibodies in contexts such as flow cytometry, immunohistochemistry, immunoprecipitation and ELISAs. A fusion protein as described also can be used in screening for agonists and antagonists to the cognate binding partner of the nonantibody portion of the fusion protein. Moreover, chimeric molecules in which the nonantibody portion contains a growth factor domain are internalized, essentially like the natural growth factor, in contrast to the s…