The United States of America As Represented by the Department of Health

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

The United States of America As Represented by the Secretary of

William J Larochelle

Stuart A Aaronson

Jacalyn H Pierce

Roy A Jensen

Karl G Csaky

Olaf Dirsch

Eddy Anglade

John F Beeler

Daniel M Sullivan

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.

Fusion proteins that include antibody and nonantibody portions

The invention is directed toward a compound comprising a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid, wherein the recombinant nucleic acid can be packaged in an adenovirus particle and wherein expression of the recombinant nucleic acid encoding the immunoadhesin results in production of the immunoadhesin protein. The recombinant nucleic acid encoding the immunoadhesin can be within an adenovirus. The invention further provides methods for delivering an immunoadhesin to a cell or a subject comprising administering to the cell or the subject an adenovirus comprising a recombinant nucleic acid encoding an immunoadhesin; producing an immunoadhesin comprising administering to a cell an adenovirus comprising a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid, whereby the cell expresses the recombinant nucleic acid encoding the immunoadhesin, thereby producing the immunoadhesin; treating an inflammatory condition in a subject comprising administering to the subject an adenovirus comprising a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid or a recombinant nucleic acid encoding an immunoadhesin inserted within an adenoviral nucleic acid, whereby a cell in the subject expresses the recombinant nucleic acid encoding the immunoadhesin and produces the immunoadhesin, thereby treating the inflammatory condition or administering to the subject a recombinant nucleic acid encoding an immunoadhesin, or an immunoadhesin, wherein the immunoadhesin is selected from the group consisting of vIL-10-IgG, IL-13-IgG, LFA-IgG, IL-2ra-IgG, IL-1ra-IgG, mutant IL-4-IgG, VLA4-IgG, IL-2-IgG, TGF-.beta.1-IgG, TGF-.beta.1.sup.223,225 -IgG, and VCAM-IgG; and methods of screening an immunoadhesin for bioactivity.

Immunoadhesins and methods of production and use thereof

Potent neutralizing monoclonal antibodies to the human .alpha. PDGF receptor (.alpha. PDGFR) and fragments thereof are described. These monoclonal antibodies specifically bind to an epitope on .alpha. PDGFR, inhibits PDGF binding with PDGF, antagonizes PDGF, and does not bind .beta. PDGFR receptor. A hybridoma cell line producing such a monoclonal antibody, methods of in vivo imaging of a pathological conditions and methods of inhibiting the growth of a neoplasia expressing .alpha. PDGFR, which use these monoclonal antibodies are also described. In vitro assays for detecting the presence of .alpha. PDGFR and for evaluating the binding affinity of a test compound are also described.

Assay and kit for the detection of .alpha. platelet derived growth

Methods of inhibiting the growth of neoplasia using a monoclonal

A novel protein tyrosine kinase (A6) exhibiting no significant similarity to any known kinase. This protein in widely expressed throughout the body and is present in a variety of vertebrates. The cDNA was expressed in bacteria as a fusion protein which was both autophosphorylated and exhibited kinase activity toward exogenous substrates. Potential uses of this invention include immunodiagnostics and antiproliferative therapeutics.

Protein tyrosine kinase A6

Method for making a monoclonal antibody, monoclonal antibodies to .alpha. P

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Gaithersburg, MD, United States of America

William J Larochelle