Dirofilaria and brugia ankyrin proteins, nucleic acid molecules, and uses thereof
The present invention relates to Dirofilaria ankyrin proteins and to Brugia ankyrin proteins; to Dirofilaria ankyrin nucleic acid molecules and to Brugia ankyrin nucleic acid molecules, including those that encode such ankyrin proteins; to antibodies raised against such ankyrin proteins; and to compounds that inhibit Dirofilaria or Brugia ankyrin function. The present invention also includes methods to identify and 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.
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Claims
1. An isolated ankyrin protein wherein said protein is encoded by a Dirofilaria or Brugia nucleic acid molecule selected from the group consisting of: a nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37 and SEQ ID NO:40; and an allelic variant of a nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37 and SEQ ID NO:40.
2. The ankyrin protein of claim 1, wherein said Dirofilaria ankyrin protein is a Dirofilaria immitis ankyrin protein, and wherein said Brugia ankyrin protein a Brugia malayi ankyrin protein.
3. The ankyrin protein of claim 1, wherein said protein, when administered to an animal, elicits an immune response against an ankyrin protein selected from the group consisting of a Dirofilaria ankyrin protein and a Brugia ankyrin protein.
4. The ankyrin protein of claim 1, wherein said protein is encoded by a nucleic acid molecule selected from the group consisting of: a nucleic acid molecule selected from the group consisting of nDiAnk.sub.937, nDiAnk.sub.936, nDiAnk.sub.1029, nDiAnk.sub.810, nDiAnk.sub.600, nDiAnk.sub.1228, nDiAnk.sub.1227, nDiAnk.sub.573, nDiAnk.sub.911, nDiAnk.sub.909, nDiAnk.sub.1096, nDiAnk.sub.1044, nDiAnk.sub.5503, nDiAnk.sub.5235, nBmAnk.sub.908, and nBmAnk.sub.906; and an allelic variant of a nucleic acid molecule selected from the group consisting of nDiAnk.sub.937, nDiAnk.sub.936, nDiAnk.sub.1029, nDiAnk.sub.810, nDiAnk.sub.600, nDiAnk.sub.1228, nDiAnk.sub.1227, nDiAnk.sub.573, nDiAnk.sub.911, nDiAnk.sub.909, nDiAnk.sub.1096, nDiAnk.sub.1044, nDiAnk.sub.5503, nDiAnk.sub.5235, nBmAnk.sub.908, and nBmAnk.sub.906.
5. An isolated ankyrin protein, wherein said protein is selected from the group consisting of: a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:15, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:28, SEQ ID NO:33 and SEQ ID NO:38; and a protein comprising an amino acid sequence encoded by an allelic variant of a nucleic acid molecule encoding a protein having an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:15, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:28, SEQ ID NO:33 and SEQ ID NO:38.
6. The ankyrin protein of claim 5, wherein said Dirofilaria ankyrin protein is a Dirofilaria immitis ankyrin protein, and wherein said Brugia ankyrin protein is a Brugia malayi ankyrin protein.
7. The ankyrin protein of claim 5, wherein said protein, when administered to an animal, elicits an immune response against an ankyrin protein selected from the group consisting of Dirofilaria ankyrin protein and a Brugia ankyrin protein.
8. An isolated ankyrin protein that is at least 75% identical to PDiAnk.sub.1745 (SEQ ID NO:33) and has the ability to bind to an antibody against PDiAnk.sub.1745.
9. An isolated ankyrin protein that is at least 90% identical to PBmAnk.sub.302 (SEQ ID NO:38) and has the ability to bind to an antibody against PbmAnk.sub.302.
10. An isolated antibody that selectively binds to an ankyrin protein as set forth in claim 1.
11. An isolated antibody that selectively binds to an ankyrin protein as set forth in claim 5.
12. A therapeutic composition to protect an animal from disease caused by a parasitic helminth, said therapeutic composition comprising the ankyrin protein of claim 1 or claim 5, or the antibody of claim 10 or claim 11.
13. The composition of claim 12, wherein said composition further comprises a component selected from the group consisting of an excipient, an adjuvant, a carrier, and a mixture thereof.
14. The composition of claim 12, wherein said disease is selected from the group consisting of heartworm disease, elephantiasis, and hydrocele.
- Bargmann, et al., 1991, Science, 251, pp. 1243-1246. Bennett, 1992, The Journal of Biological Chemistry, 267:13, pp. 8703-8706. Davis, et al., 1994, The Journal of Biological Chemistry, 269:44, pp. 27163-27166. Erttmann, et al., 1996, Tropical Medicine and International Health, 1:5, pp. 558-574. Erttmann, et al., 1996, The Journal of Biological Chemistry, 271:3, pp. 1645-1650. Erttmann, et al., 1996, FEBS Letters 390, pp. 21-24. Kordeli, et al., 1995, The Journal of Biological Chemistry, 270:5, pp. 2352-2359. Kunimoto, et al., 1991, The Journal of Cell Biology, 115:5, pp. 1319-1331. Lambert, et al., 1993, The Journal of Neuroscience, 13:9, pp. 3725-3735. Otsuka, et al., 1995, The Journal of Cell Biology, 129:4, pp. 1081-1092. Smith, et al., 1991, Proc. Natl. Acad. Sci. USA, 88, pp. 6971-6975. Srinivasan, et al., 1988, Nature, 333, pp. 177-180.
Type: Grant
Filed: Feb 26, 1998
Date of Patent: Aug 24, 1999
Assignee: Heska Corporation (Fort Collins, CO)
Inventors: Liang Tang (Fort Collins, CO), E. Scot Blehm (Fort Collins, CO)
Primary Examiner: Karen Cochrane Carlson
Law Firm: Heska Corporation
Application Number: 9/31,485
International Classification: A61K 3514; C07K 1400;
