The invention relates to: nucleic acid molecules encoding the light chain and heavy chain of feline immunoglobulin E (IgE), including species-specific regions of feline IgE; proteins encoded by the nucleic acid molecules; inhibitors to the nucleic acids and proteins; antibodies to the proteins; cells transformed with the nucleic acid molecules; assays employing the transformed cells, nucleic acids, antibodies and/or proteins or portions thereof; methods for treating IgE-mediated responses (ie. allergy) using the materials provided; methods for eliciting an immune response to IgE and kits containing the nucleic acid molecules, proteins or derivatives thereof (ie. antibodies).

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.epsilon. receptor (sometimes called "Fc.epsilon.R") binding region, is preferred. In particular, nucleic acid molecules which encode a feline IgE Fc.epsilon. 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.epsilon. 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.epsilon. interaction, comprising: contacting the test compound with a protein of the present invention; and determining whether the test compound and said protein interact.

Also provided by the present invention are methods for inhibiting an immune response to feline IgE, comprising administering at least one therapeutic composition of the present invention.

Also provided by the present invention are diagnostic kits, comprising a container comprising a at least one composition 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).

Also provided are isolated nucleic acid molecules encoding a portion of a feline IgE light chain protein, wherein said nucleic acid molecule comprises a nucleic acid sequence selected from the group consisting of:

(a) a nucleic acid sequence which has more than 84% identity to SEQ ID NO 19, and 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 selected from the group consisting of: a feline heavy chain protein which has more than 61% identity to SEQ ID NO 20, wherein said identity can be determined using the DNAsis computer program and default parameters; and a feline heavy chain protein encoded by an allelic variant of SEQ ID NO 19;

(c) a nucleic acid sequence which has more than 95% identity to a nucleic acid sequence selected from the group consisting of: SEQ ID NO 23; and SEQ ID NO 25; and

(d) 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).

Also provided are isolated proteins encoding a portion of a feline IgE light chain molecule, wherein said protein comprises 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 84% identity to SEQ ID NO 19, and wherein said identity can be determined using the DNAsis computer program and default parameters;

(b) an amino acid sequence which has more than 61% identity to SEQ ID NO 20, 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 SEQ ID NO 19; and

(d) a nucleic acid sequence which has more than 95% identity to a nucleic acid sequence selected from the group consisting of: SEQ ID NO 23; and SEQ ID NO 25.
 

Claim 1 of 2 Claims

1. An isolated protein encoded by a nucleic acid sequence consisting of SEQ ID NO:1, SEQ ID NO 4, SEQ ID NO 7, SEQ ID NO 10, SEQ ID NO 13, SEQ ID NO 16 or SEQ ID NO:28.

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