Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
2000-08-04
2002-05-21
Marschel, Ardin H. (Department: 1631)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C530S300000, C530S387100, C435S007100, C435S183000, C424S184100, C424S130100, C536S023100
Reexamination Certificate
active
06392017
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to parasitic helminth Antigen-2 (DiAg2) nucleic acid molecules, proteins encoded by such nucleic acid molecules and antibodies raised against such proteins. The present invention also includes therapeutic compositions comprising such nucleic acid molecules, proteins, and/or antibodies, as well as their use to protect animals from diseases caused by parasitic helminths.
BACKGROUND OF THE INVENTION
Parasitic helminth infections in animals, including humans, are typically treated by chemical drugs. One disadvantage with chemical drugs is that they must be administered often. For example, dogs susceptible to heartworm are typically treated monthly. Repeated administration of drugs, however, often leads to the development of resistant helminth strains that no longer respond to treatment. Furthermore, many of the chemical drugs cause harmful side effects in the animals being treated, and as larger doses become required due to the build up of resistance, the side effects become even greater. Moreover, a number of drugs only treat symptoms of a parasitic disease but are unable to prevent infection by the parasitic helminth.
An alternative method to prevent parasitic helminth infection includes administering a vaccine against a parasitic helminth. Although many investigators have tried to develop vaccines based on specific antigens, it is well understood that the ability of an antigen to stimulate antibody production does not necessarily correlate with the ability of the antigen to stimulate an immune response capable of protecting an animal from infection, particularly in the case of parasitic helminths however there is yet to be a commercially available vaccine developed for any parasitic helminth.
As an example of the complexity of parasitic helminths, the life cycle of
Dirofilaria immitis
, the falariid nematode that causes heartworm, includes a variety of life forms, each of which presents different targets, and challenges, for immunization. In a mosquito,
D. immitis
microfilariae go through two larval stages (L1 and L2) and become mature third stage larvae (L3), which can then be transmitted back to the dog when the mosquito takes a blood meal. In a dog, the L3 molt to the fourth larval stage (L4), and subsequently to the fifth stage, or immature adults. The immature adults migrate to the heart and pulmonary arteries, where they mature to adult heartworms. Adult heartworms are quite large and preferentially inhabit the heart and pulmonary arteries of an animal. Sexually mature adults, after mating, produce microfilariae which traverse capillary beds and circulate in the vascular system of the dog. In particular, heartworm is a major problem in dogs, which typically do not develop immunity upon infection (i.e., dogs can become reinfected even after being cured by chemotherapy). In addition, heartworm infection has been reported in cats, ferrets, and humans.
As such, there remains a need to identify efficacious compositions that protect animals against diseases caused by parasitic helminths such as
D. immitis
. Such compositions would preferably also protect animals from infection by such helminths.
SUMMARY OF THE INVENTION
The present invention relates to a novel product and a process to protect animals against parasitic helminth infection (e.g., prevent and/or treat such an infection). According to the present invention there are provided a parasitic helminth DiAg2 protein (e.g. a Dirofilaria DiAg2 protein) and a mimetope thereof; a parasitic helminth DiAg2 nucleic acid molecule, including those that encode such a protein; and an antibody raised against such a DiAg2 protein (i.e., an anti-parasitic helminth DiAg2 antibody).
The present invention also includes methods to obtain and/or identify such a protein, nucleic acid molecule, and antibody. Also included in the present invention is a therapeutic composition comprising such a protein, nucleic acid molecule, and/or antibody, as well as use of such a therapeutic composition to protect animals from diseases caused by parasitic helminths.
A preferred parasitic helminth DiAg2 nucleic acid molecule of the present invention includes an isolated nucleic acid molecule selected from the group consisting of: (a) a nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and SEQ ID NO:23; and (b) a nucleic acid molecule comprising an at least 24 consecutive nucleotide portion identical in sequence to a consecutive 24 nucleotide portion of a sequence as set forth in (a).
A preferred parasitic helminth DiAg2 nucleic acid molecule of the present invention includes an isolated filariid nematode nucleic acid molecule that hybridizes to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, and/or SEQ ID NO:23, under conditions comprising (a) hybridizing in a solution comprising 1×SSC and 0% formamide, at a temperature of about 37° C. and (b) washing in a solution comprising 1×SSC and 0% formamide, at a temperature of about 49° C.
The present invention also relates to a nucleic acid molecule, a recombinant molecule, a recombinant virus and a recombinant cell that includes an isolated DiAg2 nucleic acid molecule of the present invention. Also included are methods to produce such a recombinant molecule, recombinant molecule, recombinant virus and recombinant cell.
Another embodiment of the present invention includes a parasitic helminth DiAg2 protein. A preferred parasitic helminth DiAg2 protein includes an isolated protein selected from the group consisting of: (a) a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:17, and SEQ ID NO:22; (b) a protein comprising an at least 30 consecutive amino acid portion identical in sequence to a consecutive 30 amino acid portion of a sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:17, and SEQ ID NO:22; (c) a protein comprising a fragment of a protein as set forth in (a).
A preferred parasitic helminth DiAg2 protein includes an isolated filariid nematode protein comprising an amino acid sequence that is at least about 70% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:17, and/or SEQ ID NO:22 or fragments thereof.
A preferred parasitic helminth DiAg2 protein includes a Dirofilaria DiAg2 protein. More preferred DiAg2 proteins include
Dirofilaria immitis
DiAg2 proteins. A particularly preferred
D. immitis
DiAg2 protein comprises amino acid sequence SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:17, and/or SEQ ID NO:22. The present invention further relates to isolated antibodies that selectively bind to parasitic helminth DiAg2 proteins of the present invention, or to a mimetope thereof.
Yet another embodiment of the present invention is a therapeutic composition that is capable of protecting an animal from disease caused by a parasitic helminth. Such a therapeutic composition includes one or more of the following protective compounds: a parasitic helminth DiAg2 protein or a mimetope thereof; an isolated parasitic helminth DiAg2 nucleic acid molecule; an isolated antibody that selectively binds to a parasitic helminth DiAg2 protein; and/or a compound capable of inhibiting DiAg2 function identified by its ability to inhibit parasitic helminth DiAg2 function. A preferred therapeutic composition of the present invention also includes an excipient, an adjuvant and/or a carrier. Preferred DiAg2 nucleic acid molecule
Heska Corporation
Heska Corporation
Marschel Ardin H.
Zhou Shubo (Joe)
LandOfFree
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