Equine Fc epsilon receptor alpha chain proteins and uses...

Details Equine Fc epsilon receptor alpha chain proteins and uses... Equine Fc epsilon receptor alpha chain proteins and uses...

2000-02-29

2003-06-24

Chan, Christina (Department: 1644)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Amino acid sequence disclosed in whole or in part; or...

C530S350000

Reexamination Certificate

active

06582701

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to equine Fc epsilon receptor alpha chain nucleic acid molecules, proteins encoded by such nucleic acid molecules, antibodies raised against such proteins, and inhibitors of such proteins. The present invention also includes methods to detect IgE using such proteins and antibodies.
BACKGROUND OF THE INVENTION
Diagnosis of disease and determination of treatment efficacy are important tools in medicine. IgE antibody production in an animal can be indicative of disease including, for example, allergy, atopic disease, hyper IgE syndrome, internal parasite infections and B cell neoplasia. In addition, detection of IgE production in an animal following a treatment is indicative of the efficacy of the treatment, such as when using treatments intended to disrupt IgE production.
Immunological stimulation can be mediated by IgE antibodies when IgE complexes with Fc epsilon receptors. Fc epsilon receptors are found on the surface of certain cell types, such as mast cells. Mast cells store biological mediators including histamine, prostaglandins and proteases. Release of these biological mediators is triggered when IgE antibodies complex with Fc epsilon receptors on the surface of a cell. Clinical symptoms result from the release of the biological mediators into the tissue of an animal.
The discovery of the present invention includes a novel equine Fc epsilon receptor (Fc
&egr;
R) alpha chain protein and the use of such a protein to detect the presence of IgE in a putative IgE-containing composition; to identify inhibitors of biological responses mediated by an equine Fc
&egr;
R protein; and as a therapeutic compound to prevent or treat clinical symptoms that result from equine Fc
&egr;
R-mediated biological responses.
Prior investigators have disclosed the nucleic acid sequence for: the human Fc
&egr;
R alpha chain (Kochan et al.,
Nucleic Acids Res.
16:3584, 1988; Shimizu et al.,
Proc. Natl. Acad. Sci. USA
85:1907-1911, 1988; and Pang et al.,
J. Immunol.
151:6166-6174, 1993); the human Fc
&egr;
R beta chain (Kuster et al.,
J. Biol. Chem.
267:12782-12787, 1992); the human Fc
&egr;
R gamma chain (Kuster et al.,
J. Biol. Chem.
265:6448-6452, 1990); and the canine Fc
&egr;
R alpha chain (GenBank™ accession number D16413). Although the subunits of human Fc
&egr;
R have been known as early as 1988, they have never been used to identify an equine Fc
&egr;
R. Similarly, even though the canine Fc
&egr;
R chain has been known since 1993, it has never been used to identify an equine Fc
&egr;
R. Moreover, the determination of human and canine Fc epsilon receptor sequences does not indicate, suggest or predict the cloning of a novel Fc
&egr;
R gene from a different species, in particular, from an equine species. Previous investigators have found a low degree of similarity between rat, mouse and human Fc
&egr;
R&agr; (Ravtech et al., Ann. Rev. Immunol. Vol. 9, pp. 457-492, 1991). Thus, given this low degree of sequence similarity, it would appear only “obvious to try” to obtain an equine Fc
&egr;
R&agr; nucleic acid molecule and protein.
Thus, products and processes of the present invention are needed in the art that will provide specific detection of IgE, in particular equine IgE, and treatment of Fc epsilon receptor-mediated disease.
SUMMARY OF THE INVENTION
The present invention relates to a novel product and process for detecting IgE and protecting animals from Fc epsilon receptor-mediated biological responses. According to the present invention there are provided equine Fc
&egr;
R proteins and mimetopes thereof; equine Fc
&egr;
R nucleic acid molecules, including those that encode such proteins; antibodies raised against such equine Fc
&egr;
R proteins (i.e., anti-equine Fc
&egr;
R antibodies); and other compounds that inhibit the ability of equine Fc
&egr;
R protein to form a complex with IgE (i.e, inhibitory compounds or inhibitors).
The present invention also includes methods to obtain such proteins, mimetopes, nucleic acid molecules, antibodies and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, mimetopes, nucleic acid molecules, antibodies, and/or inhibitory compounds, as well as use of such therapeutic compositions to Fc epsilon receptor-mediated biological responses.
One embodiment of the present invention is an isolated nucleic acid molecule encoding an equine Fc
&egr;
R protein. The equine Fc
&egr;
R protein preferably includes: proteins comprising amino acid sequences SEQ ID NO:2, SEQ ID NO:7 and SEQ ID NO:12; and proteins encoded by allelic variants of nucleic acid molecules encoding a protein comprising any of the amino acid sequences. Particularly preferred equine Fc
&egr;
R nucleic acid molecules include: nucleic acid molecules comprising nucleic acid sequences SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8 and SEQ ID NO:11 and nucleic acid molecules comprising allelic variants of nucleic acid molecules comprising nucleic acid sequences SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8 and SEQ ID NO:11.
The present invention also includes an isolated equine Fc
&egr;
R protein. A preferred equine Fc
&egr;
R protein is encoded by a nucleic acid molecule that hybridizes under stringent hybridization conditions to a nucleic acid sequence including SEQ ID NO:3, SEQ ID NO:5 and SEQ ID NO:8. Particularly preferred equine Fc
&egr;
R proteins include at least one of the following amino acid sequences: SEQ ID NO:2, SEQ ID NO:7 and SEQ ID NO:12.
The present invention also relates to recombinant molecules, recombinant viruses and recombinant cells that include equine Fc
&egr;
R nucleic acid molecules of the present invention. Also included are methods to produce such nucleic acid molecules, recombinant molecules, recombinant viruses and recombinant cells.
The present invention also includes detection methods and kits that detect IgE. One embodiment of the present invention is a method to detect IgE comprising: (a) contacting an isolated equine Fc
&egr;
R molecule with a putative IgE-containing composition under conditions suitable for formation of a Fc
&egr;
R molecule:IgE complex; and (b) determining the presence of IgE by detecting the Fc
&egr;
R molecule:IgE complex, the presence of the FC
&egr;
R molecule:IgE complex indicating the presence of IgE. A preferred equine Fc
&egr;
R molecule is one in which a carbohydrate group of the equine Fc
&egr;
R molecule is conjugated to biotin.
Another embodiment of the present invention is a method to detect IgE comprising: (a) contacting a recombinant cell with a putative IgE-containing composition under conditions suitable for formation of a recombinant cell:IgE complex, in which the recombinant cell comprises an equine Fc
&egr;
R molecule; and (b) determining the presence of IgE by detecting the recombinant cell:IgE complex, the presence of the recombinant cell:IgE complex indicating the presence of IgE. A preferred method to detect IgE comprises: (a) immobilizing the Fc
&egr;
R molecule on a substrate; (b) contacting the Fc
&egr;
R molecule with the putative IgE-containing composition under conditions suitable for formation of a Fc
&egr;
R molecule:IgE complex bound to the substrate; (c) removing non-bound material from the substrate under conditions that retain Fc
&egr;
R molecule:IgE complex binding to the substrate; and (d) detecting the presence of the Fc
&egr;
R molecule:IgE complex. Another preferred method to detect IgE comprises: (a) immobilizing a specific antigen on a substrate; (b) contacting the antigen with the putative IgE-containing composition under conditions suitable for formation of an antigen:IgE complex bound to the substrate; (c) removing non-bound material from the substrate under conditions that retain antigen:IgE complex binding to said substrate; and (d) detecting the presence of the antigen:IgE complex by contacting the antigen:IgE complex with said Fc
&egr;
R molecule. Another preferred method to detect IgE comprises: (a) immobilizing a

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