The United States of America, As Represented by the Secretary, Department of Health and Human Services

Olaf Dirsch

Stuart A Aaronson

William J Larochelle

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:CH :CH segment which lacks a CH 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 situation that generally pertains with respect to antibodies which are directed to external receptor domains.

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Bethesda, MD, United States of America

Olaf Dirsch