Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Reexamination Certificate
2000-08-08
2001-09-18
Nolan, Patrick J. (Department: 1644)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
C424S130100, C424S139100, C424S141100, C530S388100, C530S387100, C530S387900, C530S388260
Reexamination Certificate
active
06290958
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to flea epoxide hydrolase nucleic acid molecules, proteins encoded by such nucleic acid molecules, antibodies raised against such proteins, and inhibitors of such proteins. The present invention also includes therapeutic compositions comprising such nucleic acid molecules, proteins; antibodies, and/or other inhibitors, as well as their use to protect an animal from hematophagous arthropod infestation.
BACKGROUND OF THE INVENTION
Hematophagous arthropod infestation of animals is a health and economic concern because hematophagous arthropods are known to cause and/or transmit a variety of diseases. Hematophagous arthropods directly cause a variety of diseases, including allergies, and also carry a variety of infectious agents including, but not limited to, endoparasites (e.g., nematodes, cestodes, trematodes and protozoa), bacteria and viruses. In particular, the bites of hematophagous arthropods are a problem for animals maintained as pets because the infestation becomes a source of annoyance not only for the pet but also for the pet owner who may find his or her home generally contaminated with insects. As such, hematophagous arthropods are a problem not only when they are on an animal but also when they are in the general environment of the animal.
Bites from hematophagous arthropods are a particular problem because they not only can lead to disease transmission but also can cause a hypersensitive response in animals which is manifested as disease. For example, bites from fleas can cause an allergic disease called flea, allergic (or allergy) dermatitis (FAD). A hypersensitive response in animals typically results in localized tissue inflammation and damage, causing substantial discomfort to the animal.
The medical importance of arthropod infestation has prompted the development of reagents capable of controlling arthropod infestation. Commonly encountered methods to control arthropod infestation are generally focused on use of insecticides. While some of these products are efficacious; most, at best, offer protection of a very limited duration. Furthermore, many of the methods are often not successful in reducing arthropod populations. In particular, insecticides have been used to prevent hematophagous arthropod infestation of animals by adding such insecticides to shampoos, powders, collars, sprays, foggers and liquid bath treatments (i.e., dips). Reduction of hematophagous arthropod infestation on the pet has been unsuccessful for one or more of the following reasons: (1) failure of owner compliance (frequent administration is required); (2) behavioral or physiological intolerance of the pet to the pesticide productor means of administration; and (3) the emergence of hematophagous arthropod populations resistant to the prescribed dose of pesticide. Hematophagous arthropod populations, however, have been found to become resistant to insecticides.
Juvenile hormone (JH) regulates growth and development of immature insects, and is involved in reproductive processes in adult insects. JH levels are controlled by two degradative enzymes, juvenile hormone esterase and juvenile hormone epoxide hydrolase.
Prior investigators have described insect juvenile hormone epoxide hydrolase (JHEH) protein biochemistry, for example, Touhara et al.,
J. Biol. Chem
., 268:19604-19609, 1993 and Khlebodarova et al.,
Insect Biochem. Molec Biol
, 26:829-835, 1996. Prior investigators ave described certain insect epoxide hydrolase (EH) nucleic acid and amino acid sequences, for example, Wojtasek et al.,
Biochem. Biophys. Res. Comm
., 220:323-329, 1996 describes
Manduca sexta
JHEH sequences and Roe et al.,
Arch. Insect Biochem. Physiol
., 32:527-535, 1996. Mammalian EH genes have been cloned, none of which have more than 40% identity with the nucleic acid molecules of the present invention.
Identification of an EH of the present invention is unexpected, however, because even the most similar nucleic acid sequence identified by previous investigators could not be used to identify an EH of the present invention. In addition, identification of an EH protein of the present invention is unexpected because the inventors of the present invention identified highly conserved regions of epoxide hydrolase sequences suitable for the production of degenerate primers. Production of primers to such conserved regions is not taught or suggested by previous investigators.
In summary, there remains a need to develop a reagent and a method to protect animals from hematophagous arthropod infestation.
SUMMARY OF THE INVENTION
The present invention relates to a novel product and process for protection of animals from arthropod infestation. According to the present invention there are provided arthropod epoxide hydrolase (EH) proteins and mimetopes thereof; arthropod nucleic acid molecules, including those that encode such proteins; antibodies raised against such EH proteins (i.e., anti-arthropod EH antibodies); and compounds that inhibit arthropod EH activity (Le, inhibitory compounds or inhibitors).
The present invention also includes methods to obtain such proteins, mimetopes, nucleic acid molecules, antibodies and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, mimetopes, nucleic acid molecules, antibodies, and/or inhibitory compounds, as well as use of such therapeutic compositions to protect animals from arthropod infestation.
Identification of an EH of the present invention is unexpected, however, because the most similar nucleic acid sequence identified by previous investigators could not be used to identify an EH of the present invention. In addition, identification of an EH protein of the present invention is unexpected because the inventors of the present invention identified highly conserved regions of epoxide hydrolase sequences suitable for the production of degenerate primers. Production of primers to such conserved regions is not taught or suggested by previous investigators.
One embodiment of the present invention is an isolated nucleic acid molecule that hybridizes under stringent hybridization conditions with a gene comprising a nucleic acid sequence including 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:15, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26 and/or SEQ ID NO:27.
The present invention. also includes a nucleic acid molecule that hybridizes under stringent hybridization conditions with a complement of a nucleic acid molecule encoding a protein comprising at least one of the following amino acid sequences: SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:20, SEQ ID NO:23 and/or SEQ ID NO:28. A preferred nucleic acid molecule of the present invention includes a nucleic acid molecule comprising a nucleic acid sequence including 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 TD NO:15, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26and/or SEQ ID NO:27, and an allelic variant of a nucleic acid molecule comprising any of the nucleic acid sequences.
The present invention also relates to recombinant molecules, recombinant viruses and recombinant cells that include a nucleic acid molecule of the present invention. Also included are methods to produce such nucleic acid molecules, recombinant molecules, recombinant viruses and recombinant cells.
The present invention also relates to mimetopes of arthropod EH proteins as well as to isolated antibodies that selectively bind to arthropod EH proteins or mimetopes thereof. Also included are methods, including recombinant methods, to produce proteins, mimetopes and antibodies of the present invention.
Another embodiment of the present invention is a method to identify a compound capable of inhibiting arthropod EH activity, the method comprising: (a) contacting an isolated hematophagous arthropod EH with a putative inhibitory compound under conditions in which, in the absence of the compoun
Brandt Kevin S.
Lo Katherine Callies
Silver Gary M.
Wisnewski Nancy
Heska Corporation
Heska Corporation
Huynh Phuong N.
Nolan Patrick J.
LandOfFree
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