Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-02-29
2001-09-04
Gambel, Phillip (Department: 1644)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100, C435S455000, C435S471000, C435S252300, C435S320100, C435S069100
Reexamination Certificate
active
06284881
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to feline 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.
Until the discovery of the present invention, detection of IgE in samples obtained from animals has been hindered by the absence of suitable reagents for detection of IgE. Various compounds have been used to detect IgE in IgE-containing compositions. In particular, antibodies that bind selectively to epsilon idiotype antibodies (i.e., anti-IgE antibodies) have been used to detect IgE. These anti-IgE antibodies, however, can cross-react with other antibody idiotypes, such as gamma isotype antibodies. Also, creation of reagents capable of inhibiting the activity of Fc epsilon receptors has been limited.
The discovery of the present invention includes a novel feline Fc epsilon receptor alpha chain (Fc&egr;R&agr;) 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 a feline Fc&egr;R&agr; protein; and as a therapeutic compound to prevent or treat clinical symptoms that result from feline Fc&egr;R&agr;-mediated biological responses. When used in an assay to detect IgE, a feline Fc&egr;R&agr; protein provides an advantage over, for example anti-IgE antibodies, to detect IgE because a feline Fc&egr;R&agr; protein can bind to an IgE with more specificity (i.e., less idiotype cross-reactivity) and more sensitivity (i.e., affinity) than anti-IgE binding antibodies.
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 a feline Fc&egr;R. Similarly, even though the canine Fc&egr;R chain has been known since 1993, it has never been used to identify a feline 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&agr; gene from a different species, in particular, from a feline species.
Thus, products and processes of the present invention are needed in the art that will provide specific detection of 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 feline Fc&egr;R&agr; proteins and mimetopes thereof; feline Fc&egr;R&agr; nucleic acid molecules, including those that encode such proteins; antibodies raised against such feline Fc&egr;R&agr; proteins (i.e., anti-feline Fc&egr;R&agr; antibodies); and other compounds that inhibit the ability of feline Fc&egr;R&agr; 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, andlor 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 a feline Fc&egr;R&agr; protein. The feline Fc&egr;R&agr; protein preferably includes: proteins comprising amino acid sequences SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO: 12 and SEQ ID NO:13; and proteins encoded by allelic variants of a nucleic acid molecules encoding a protein comprising any of the amino acid sequences. Particularly preferred feline Fc&egr;R&agr; 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, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16; 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, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO: 15 and SEQ ID NO:16.
The present invention also includes an isolated feline Fc&egr;R&agr; protein. A preferred feline Fc&egr;R&agr; 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, SEQ ID NO:8, SEQ ID NO:15 and SEQ ID NO:16. Particularly preferred feline Fc&egr;R&agr; proteins include at least one of the following amino acid sequences: SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:12 and SEQ ID NO:13.
The present invention also relates to recombinant molecules, recombinant viruses and recombinant cells that include feline Fc&egr;R&agr; 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 feline Fc&egr;R&agr; molecule with a putative IgE-containing composition under conditions suitable for formation of a Fc&egr;R&agr; molecule:IgE complex; and (b) determining the presence of IgE by detecting the Fc&egr;R&agr; molecule:IgE complex, the presence of the Fc&egr;R&agr; molecule:IgE complex indicating the presence of IgE. A preferred feline Fc&egr;R&agr; molecule is one which a carbohydrate group of the feline Fc&egr;R&agr; 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 a feline Fc&egr;R&agr; 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&agr; molecule on a substrate; (b) contacting the Fc&egr;R&agr; molecule with the putative IgE-containing composition under conditions suitable for formation of a Fc&egr;R&agr; molecule:IgE complex bound to the substrate; (c) removing
Frank Glenn R.
Porter James P.
Rushlow Keith E.
Wassom Donald L.
Weber Eric R.
Gambel Phillip
Heska Corporation
Heska Corporation
Roark Jessica H.
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