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 Department of Health

The United States of America As Represented by the Secretary of

Jacalyn H Pierce

Stuart A Aaronson

Toshimitsu Matsui

Roy A Jensen

William J Larochelle

William LaRochelle

Bharvin K R Patel

A DNA sequence which encodes a human type &#x3b1; platelet derived growth factor receptor protein which preferentially binds to the AA homodimer and AB heterodimer forms of platelet derived growth factor and also binds the BB homodimer at high affinity, is described. Substantially pure human a platelet derived growth factor receptor protein and methods for recombinantly producing human &#x3b1; platelet derived growth factor receptor protein are also described.

Compositions of alpha platelet derived growth factor receptor nucleic acid and protein and method of making

Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce a hitherto unknown type of human Platelet-Derived Growth Factor (PDGF) receptor protein free of other PDGF receptors. These proteins can be produced from DNA segments in cells in various functional forms. These forms variously enable biochemical and functional studies of these novel receptors as well as production of antibodies. Means are described for determining the level of expression of genes for specific types of PDGF receptor proteins, for example, by measuring mRNA in cells with PDGF receptor type-specific DNA probes or by measuring antigen in biological samples with type-specific antibodies.

Methods for identifying alpha PDGFR agonists and antagonists

Antibodies for the alpha platelet-derived growth factor receptor

The present invention provides an isolated nucleic acid encoding the polypeptide Stat6b, having an amino acid sequence of Stat6 wherein a deletion in the nucleic acid is present, encompassing the last base pair of codon 39 of Stat6 and continuing through to and including codon 86 of Stat6 and an isolated polypeptide, Stat6b, having an amino acid sequence of Stat6 wherein amino acids 39-86 are deleted at the amino terminus. Also provided is an isolated nucleic acid encoding the polypeptide Stat6c, having an amino acid sequence of Stat6 wherein amino acids 537-564 are deleted and an isolated polypeptide, Stat6c, having an amino acid sequence of Stat6 wherein amino acids 537-564 are deleted. Methods of producing the polypeptide Stat6b and polypeptide Stat6c are also provided, comprising culturing cells comprising nucleic acid encoding the polypeptide Stat6b or the polypeptide Stat6c under conditions whereby the polypeptide Stat6b or the polypeptide Stat6c is produced.

Attenuated and dominant negative variant cDNAs of Stat6: Stat6b and Stat6c

Recombinant DNA technology was used to clone encoding nucleic acids for the human alpha platelet-derived growth factor receptor (PDGF-R type alpha). Peptides corresponding to the predicted sequence of this type and of the PDGF-R type beta were used to elicit antibodies specific for either type of the PDGF-R. Immunoassays are described for determining the level of PDGF-R type alpha in biological samples with the PDGF-R type alpha-specific antibodies.

Immunoassays for the alpha platelet-derived growth factor receptor

Method of detecting the expression of alpha platelet-derived growth

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.

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Pukalani, HI, United States of America

Jacalyn H Pierce