Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-01-08
2001-05-29
Ulm, John (Department: 1646)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S069100, C435S252300, C435S320100, C530S350000
Reexamination Certificate
active
06239268
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to cell surface receptors, and more specifically, to Interleukin-1 Type 3 receptors.
BACKGROUND OF THE INVENTION
Interleukin-1 (“IL-1”) is a cytokine which is known to be a key mediator of immunological and pathological responses to stress, infection and antigenic challenge (Oppenheim et al.,
Immunol. Today
7:45-46, 1986; Dinarello,
FASEB J.
2:108-115, 1988; and Mizel,
FASEB J.
3:2379-2388, 1989). In addition, IL-1 is known to have a variety of effects on the brain and central nervous system. For example, IL-1 has been postulated to be involved in the induction of fever (Kluger,
Physiol. Rev.
71:93-127, 1991), increased duration of slow wave sleep (Opp et al.,
Am. J. Physiol.
260:R52-R58, 1991), decreased appetite (McCarthy et al.,
Am. J. Clin. Nutr.
42:1179-1182, 1985), activation of the hypothalamic-pituitary-adrenal (“HPA”) axis (Woloski et al.,
Science
230:1035-1037, 1985), and inhibition of the hypothalamic-pituitary-gonadal axis (River and Vale,
Endocrinology
124:2105-2109, 1989).
In light of the above-noted effects of IL-1 (as well as many others), substantial effort has been undertaken in order to identify receptors for IL-1. Briefly, at least two types of receptors are known to be expressed on the surface of certain immune cells in both human and murine derived lines. Type I receptors bind both IL-1&agr; and IL-1&bgr;, and can be found on T cells, fibroblasts, keratinocytes, endothelial cells, synovial lining cells, chondrocytes and hepatocytes (U.S. Pat. Nos. 4,968,607, 5,081,228, and 5,180,812; Chizzonite et al.,
PNAS
86:8029-8033, 1989; Dinarello et al.,
Blood
77:1627-1652, 1991). Type II receptors can be found on various B cell lines, including the Raji human B-cell lymphoma line (Bomsztyk et al.,
PNAS
86:8034-8038, 1989; Horuk et al.,
J. Biol. Chem.
262:16275-16278, 1987; Horuk and McCubrey,
Biochem. J.
260:657-663, 1989).
The present invention provides new, previously unidentified Interleukin receptors, designated Interleukin-1 Type 3 receptors (“IL-1-3R”). In addition, the present invention provides compositions and methods which utilize such receptors, as well as other, related advantages.
SUMMARY OF THE INVENTION
Briefly stated, the present invention provides compositions and methods which comprise Interleukin-1 Type 3 receptors. Within one aspect of the present invention isolated nucleic acid molecules are provided which encode Interleukin-1 Type 3 receptors. Within one embodiment, the isolated nucleic acid molecules comprise the sequence of nucleotides in Sequence I.D. No. 1, from nucleotide number 129 to nucleotide number 1814. Within another embodiment, the isolated nucleic acid molecules encode a protein having the amino acid sequence of Sequence I.D. No. 2, from amino acid number 1 to amino acid number 562. Within other embodiments, isolated nucleic acid molecules are provided in Sequence I.D. No. 3, from nucleotide number 89 to nucleotide number 1771. Within another embodiment, the nucleic acid molecules encode a protein having the amino acid sequence of Sequence I.D. No. 4, from amino acid number 1 to amino acid number 561. Nucleic acid molecules which encode IL-1 Type 3 receptors of the present invention may be isolated from virtually any warm-blooded animal, including for example, humans, macaques, horses, cattle, sheep, pigs, dogs, cats, rats and mice.
Within related aspects of the present invention, isolated nucleic acid molecules are provided which encode soluble Interleukin-1 Type 3 receptors. Within one embodiment, the isolated nucleic acid molecules comprise the sequence of nucleotides in Sequence I.D. No. 1, from nucleotide number 129 to nucleotide number 1136. Within other embodiments, the isolated nucleic acid molecules encode a protein having the amino acid sequence of Sequence I.D. No. 2, from amino acid number 1 to amino acid number 336. Within another embodiment, the nucleic acid molecules comprise the sequence of nucleotides in Sequence I.D. No. 3, from nucleotide number 89 to nucleotide number 1102. Within yet another embodiment, the nucleic acid molecules encode a protein having the amino acid sequence of Sequence I.D. No. 4, from amino acid number 1 to amino acid number 338. As above, nucleic acid molecules which encode soluble IL-1 Type 3 receptors of the present invention may be isolated from virtually any warm-blooded animal, including for example, humans, macaques, horses, cattle, sheep, pigs, dogs, cats, rats and mice.
Within other aspects of the present invention, expression vectors are provided which are capable of expressing the above-described nucleic acid molecules. Within one embodiment, such vectors comprise a promoter operably linked to one of the above-described nucleic acid molecules. Within other embodiments, recombinant viral vectors are provided which are capable of directing the expression of one of the above described nucleic acid molecules. Representative examples of such viral vectors include retroviral vectors, adenoviral vectors, and herpes simplex virus vectors. Also provided by the present invention are host cells containing one of the above-described recombinant vectors.
Within other aspects of the present invention, isolated Interleukin-1 Type 3 receptors are provided. Within one embodiment, such receptors have the amino acid sequence of Sequence I.D. No. 2, from amino acid number 1 to amino acid number 562. Within another embodiment, the receptors have the sequence of Sequence I.D. No. 4, from amino acid number 1 to amino acid number 561. Within yet further aspects of the invention, isolated soluble Interleukin-1 Type 3 receptors are provided. Within one embodiment, the isolated soluble Interleukin-1 Type 3 receptors have the amino acid sequence of Sequence I.D. No. 2, from amino acid number 1 to amino acid number 336. Within another embodiment, the soluble receptors have the sequence of Sequence I.D. No. 4, from amino acid number 1 to amino acid number 338.
Within other aspects of the invention, isolated antibodies capable of specifically binding to an Interleukin-1 Type 3 receptor are provided. Within one embodiment, the antibody may be selected from the group consisting of polyclonal antibodies, monoclonal antibodies, and antibody fragments. Within other embodiments, antibodies are provided which are capable of blocking the binding of IL-1 to an Interleukin-1 Type 3 receptor. Within preferred embodiments, the antibody is selected from the group consisting of murine and human antibodies. In addition to antibodies, the present invention also provides hybridomas which produces an antibody as described above.
Within yet another aspect of the present invention, nucleic acid molecules are provided which are capable of specifically hybridizing to a nucleic acid molecule encoding any of the Interleukin-1 Type 3 receptors described above. Such molecules may be between at least “y” nucleotides long, wherein “y” is any integer between 14 and 2044, and furthermore, may be selected suitable for use as probes or primers described below. Particularly preferred probes of the present invention are at least 18 nucleotides in length.
These and other aspects of the present invention will become evident upon reference to the following detailed description and attached drawings. In addition, various references are set forth below which describe in more detail certain procedures or compositions (e.g., plasmids, etc.), and are therefore incorporated by reference in their entirety.
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Takao et al., “Species differences in [125I]interleukin-1 binding in brain, endocrine and immune tissues,”Brain Research 623:172-176, 1993.
Hart et al., “An mRNA homologous to interleukin-1 receptor type-I is expressed in
Clevenger William R.
DeSouza Errol B.
Liaw Chen Wang
Lovenberg Timothy W.
Oltersdorf Tilman
Neurocrine Biosciences Inc.
Seed Intellectual Property Law Group PLLC
Ulm John
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