Feline immunoglobulin E molecules and compositions there of

Details Feline immunoglobulin E molecules and compositions there of Feline immunoglobulin E molecules and compositions there of

2000-01-07

2003-06-03

Gambel, Phillip (Department: 1644)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S023100, C536S023500, C514S04400A

Reexamination Certificate

active

06573372

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to the field of feline IgE-mediated responses, and materials and methods useful to alter natural process related to IgE-mediated responses. The present invention therefore relates to vaccine technology, small molecule/antibody technology, molecular biology tools, and immunological techniques related to feline IgE and its function.
BACKGROUND OF THE INVENTION
Allergic responses in mammals are known to be mediated by immunoglobulin E. IgE molecules bind the Fc&egr; receptor on mast cells and, when complexed with antigen, trigger a cascade of events that leads to the release of allergic mediators (ie. histamine, prostaglandins and proteases). Thus, interference with the IgE/Fc&egr; receptor interaction is an avenue for controlling allergic responses. Interference with the IgE antibody/Fc&egr; receptor interaction will also affect the pathology of atopic disease, hyper IgE syndrome, internal parasite infections and B cell neoplasia.
The species-specific portion of the IgE, the IgE constant region (on the heavy chain and involved in Fc&egr; receptor binding) is of particular importance in design and manufacture of compounds useful to interfere with the IgE/Fc&egr; receptor interaction, because compounds which are specific for this region produce little interference with non-IgE/receptor interactions. Moreover, the IgE constant region can be utilized in the design and manufacture of vaccines useful to elicit species- and immunoglobulin-specific anti-IgE immune responses.
The DNA and amino acid sequences of IgE molecules from several species, including human, rat, mouse and dog, have been reported. Peptides derived from known IgE sequences have been used to generate antibodies which alter IgE function. U.S. Pat. No. 5,091,313 is directed to the prevention or control of IgE-mediated allergic symptoms through the use of monoclonal or polyclonal antibodies raised against epitopes present in B cell-associated or soluble human IgE. WO 90/15878 discloses the use of peptides derived from human, rat or mouse IgE sequences to generate antibodies which inhibit IgE-mediated mast cell degranulation. U.S. Pat. No. 4,223,016 discloses the use of peptides derived from IgE sequences for allergic desensitization. U.S. Pat. No. 5,629,415 discloses the canine IgE sequence and uses therefor.
SUMMARY OF THE INVENTION
The present invention provides isolated nucleic acid molecules which encode a portion of the heavy chain of feline IgE, isolated proteins encoded by the nucleic acid molecules, recombinant constructs and cells comprising the nucleic acid compounds and/or proteins, antibodies to the isolated proteins, therapeutic compositions useful for treating feline IgE-mediated responses (including i.e., vaccines), methods for treating feline IgE-mediated responses, methods for eliciting a feline IgE-mediated immune response, and kits comprising the materials provided. The present invention also provides nucleic acid molecules, proteins and methods related to the feline IgE light chain.
The present invention therefore provides isolated nucleic acid molecules encoding a portion of a feline IgE heavy chain molecule, wherein said nucleic acid molecules comprise a nucleic acid sequence selected from the group consisting of:
(a) a nucleic acid sequence which has more than 82% identity to a nucleic acid sequence selected from the group consisting of: SEQ ID NO 1; and SEQ ID NO 28, wherein said identity can be determined using the DNAsis computer program and default parameters;
(b) a nucleic acid sequence which encodes a feline heavy chain protein which has more than 76% identity to an amino acid sequence selected from the group consisting of: SEQ ID NO 2; and SEQ ID NO 29, wherein said identity can be determined using the DNAsis computer program and default parameters;
(c) a nucleic acid sequence which encodes and a feline heavy chain protein encoded by an allelic variant of a nucleic acid sequence selected from the group consisting of: SEQ ID NO 1; and SEQ ID NO 28; and
(d) a nucleic acid sequence which has more than 90% identity to a nucleic acid sequence selected from the group consisting of: SEQ ID NO 3; SEQ ID NO 4; SEQ ID NO 6; SEQ ID NO 7; SEQ ID NO 9; SEQ ID NO 10; SEQ ID NO 12; SEQ ID NO 13; SEQ ID NO 15; SEQ ID NO 16; SEQ ID NO 18; and SEQ ID NO 31; and
(e) a nucleic acid molecule fully complementary to a nucleic acid molecule selected from the group consisting of: a nucleic acid molecule of (a); a nucleic acid molecule of (b); and a nucleic acid molecule of (c).
The preferred nucleic acid molecules are those with immunological significance. At the time of filing, nucleic acid molecules which encode those which encode the constant region, specifically those which encode a Fc&egr; receptor (sometimes called “Fc&egr;R”) binding region, is preferred. In particular, nucleic acid molecules which encode a feline IgE Fc&egr; receptor binding region and which comprises SEQ ID NO 4, SEQ ID NO 7 or SEQ ID NO 10 are preferred. Also provided is a nucleic acid molecule which encodes a feline IgE constant region and comprises SEQ ID NO 13.
The present invention also provides nucleic acid molecules which encode a feline IgE light chain protein and which comprise a nucleic acid molecule which encodes a protein with more than 84% identity to SEQ ID NO 19, with a nucleic acid molecule which comprises SEQ ID NO 19 being preferred.
The present invention also comprises expression vectors and recombinant cells comprising the present nucleic acid molecules. Also provided are fusion protein constructs comprising the present nucleic acid compounds.
The present invention also comprises isolated proteins encoding a portion of a feline IgE heavy chain molecule, wherein said proteins comprise an amino acid sequence selected from the group consisting of:
(a) an amino acid sequence encoded by a nucleic acid sequence which has more than 82% identity to a nucleic acid sequence selected from the group consisting of: SEQ ID NO 1; and SEQ ID NO: 28, wherein said identity can be determined using the DNAsis computer program and default parameters;
(b) an amino acid sequence which has more than 76% identity to an amino acid sequence selected from the group consisting of: SEQ ID NO 2; and SEQ ID NO: 29, wherein said identity can be determined using the DNAsis computer program and default parameters;
(c) an amino acid sequence encoded by an allelic variant of a nucleic acid sequence selected from the group consisting of: SEQ ID NO 1; and SEQ ID NO: 28; and
(d) an amino acid sequence encoded by a a nucleic acid sequence which has more than 90% identity to a nucleic acid sequence selected from the group consisting of: SEQ ID NO 3; SEQ ID NO 4; SEQ ID NO 6; SEQ ID NO 7; SEQ ID NO 9; SEQ ID NO 10; SEQ ID NO 12; SEQ ID NO 13; SEQ ID NO 15; SEQ ID NO 16; SEQ ID NO 18; SEQ ID NO 28; and SEQ ID NO 30.
The preferred embodiments of this aspect of the present invention include those proteins capable of binding to Fc&egr; receptor, in particular, SEQ ID NO 5, SEQ ID NO 8, SEQ ID NO 11 and SEQ ID NO 14.
In another embodiment, there are provided antibodies selective for a protein of the present invention. In particular, antibodies designated H-100, H-101, H-102, H-103, H-106 are preferred.
In another embodiment, there are provided therapeutic compositions useful for inhibiting an immune response to feline IgE, wherein said therapeutic composition is selected from the group consisting of:
(a) a nucleic acid molecule of the present invention;
(b) a protein encoded by a nucleic acid of (a);
(c) an inhibitor of a nucleic acid of (a); and
(d) an inhibitor of a protein of (b).
Preferred embodiments of this aspect of the present invention are antibodies selective for the proteins of the present invention, in particular, H-100, H-101, H-102, H-103, H-106 are preferred.
Also provided by the present invention are methods to identify the ability of a test compound to interfere with IgE/Fc&egr; interaction, comprising: contacting the test compound with a protein of the present invention; and determining whether th

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