Parasitic helminth cuticlin proteins and uses thereof
AssigneeHeska Corporation
InventorsRamaswamy Chandrashekar, Tony H. Morales
Life of this patent
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Abstract
The present invention relates to: parasitic helminth cuticlin proteins; parasitic helminth cuticlin nucleic acid molecules, including those that encode such cuticlin proteins; antibodies raised against such cuticlin proteins; and compounds that inhibit parasitic helminth cuticlin activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to protect animals from diseases caused by parasitic helminths.
Claims20
An isolated Dirofilaria immitis nucleic acid molecule, wherein said Dirofilaria immitis nucleic acid molecule hybridizes in a solution comprising 2×SSC and 0% formamide, at a temperature of 37° C., and washing in 1×SSC and 0% formamide at a temperature of 64° C., to a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:10.
An isolated nucleic acid molecule selected from the group consisting of:
- (a) an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:16, and SEQ ID NO:18;
- and (b) an isolated Dirofilaria immitis nucleic acid molecule comprising a homologue of any of said nucleic acid molecules of (a), or a complement of any of said homologues, wherein said homologue encodes a protein that elicits an immune response against a protein selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9, and wherein said homologue has at least a 50 contiguous nucleotide portion identical in sequence to a 50 contiguous nucleotide portion of a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10.
An isolated Dirofilaria immitis protein, wherein said Dirofilaria immitis protein is encoded by a nucleic acid molecule that hybridizes in a solution comprising 2×SSC and 0% formamide, at a temperature of 37° C., and washing in 1×SSC and 0% formamide at a temperature of 64° C., to a nucleic acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, and SEQ ID NO:10.
A therapeutic composition that, when administered to a host animal, inhibits molting of filariid larvae, said therapeutic composition comprising:
- an excipient;
- and a protective compound selected from the group consisting of:
- (a) an isolated Dirofilaria immitis protein encoded by a nucleic acid molecule that hybridizes in a solution comprising 2×SSC and 0% formamide, at a temperature of 37° C., and washing in 1×SSC and 0% formamide at a temperature of 64° C., to a nucleic acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, and SEQ ID NO:10;
- (b) an isolated protein selected from the group consisting of (i) a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:9, and SEQ ID NO:17, and (ii) an isolated Dirofilaria immitis protein comprising a homologue of a protein of (i), wherein said homologue comprises at least one epitope that elicits an immune response against a protein selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9, and wherein said homologue has at least a 15 contiguous amino acid portion identical in sequence to a 15 contiguous amino acid portion of a sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9;
- (c) an isolated Dirofilaria immitis nucleic acid molecule that hybridizes in a solution comprising 2×SSC and 0% formamide, at a temperature of 37° C., and washing in 1×SSC and 0% formamide at a temperature of 64° C., to a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:10;
- (d) an isolated nucleic acid molecule selected from the group consisting of (i) an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:16, and SEQ ID NO:18, and (ii) an isolated Dirofilaria immitis nucleic acid molecule comprising a homologue of any of said nucleic acid molecules of (i), or a complement of any of said homologues, wherein said homologue encodes a protein that elicits an immune response against a protein selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9, and wherein said homologue has at least a 50 contiguous nucleotide portion identical in sequence to a 50 contiguous nucleotide portion of a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10;
- (e) an isolated antibody that selectively binds to a protein having an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9;
- and (f) an inhibitor of filariid cuticlin activity identified by its ability to inhibit the activity of a filariid cuticlin protein having an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9.
A method to inhibit molting of filariid larvae in an animal, said method comprising administering to said animal a composition comprising a protective compound selected from the group consisting of:(a) an isolated Dirofilaria immitis protein encoded by a nucleic acid molecule that hybridizes in a solution comprising 2×SSC and 0% formamide, at a temperature of 37° C., and washing in 1×SSC and 0% formamide at a temperature of 64° C., to a nucleic acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, and SEQ ID NO:10;
- (b) an isolated protein selected from the group consisting of (i) a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:9, and SEQ ID NO:17, and (ii) an isolated Dirofilaria immitis protein comprising a homologue of a protein of (i), wherein said homologue comprises at least one epitope that elicits an immune response against a protein selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9, and wherein said homologue has at least a 15 contiguous amino acid portion identical in sequence to a 15 contiguous amino acid portion of a sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9;
- (c) an isolated Dirofilaria immitis nucleic acid molecule that hybridizes in a solution comprising 2×SSC and 0% formamide, at a temperature of 37° C., and washing in 1×SSC and 0% formamide at a temperature of 64° C., to a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:10;
- (d) an isolated nucleic acid molecule selected from the group consisting of (i) an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:16, and SEQ ID NO:18, and (ii) an isolated Dirofilaria immitis nucleic acid molecule comprising a homologue of any of said nucleic acid molecules of (i), or a complement of any of said homologues, wherein said homologue encodes a protein that elicits an immune response against a protein selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9, and wherein said homologue has at least a 50 contiguous nucleotide portion identical in sequence to a 50 contiguous nucleotide portion of a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10;
- (e) an isolated antibody that selectively binds to a protein having an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9;
- and (f) an inhibitor of filariid cuticlin activity identified by its ability to inhibit the activity of a filariid cuticlin protein having an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:9.
Dependencies are inferred from the claim text.