Interleukin-15 receptors

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C424S198100, C530S350000

Reexamination Certificate

active

06548065

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates generally to cytokine receptors, and more specifically, to Interleukin-15 receptors.
Interleukin-15 (IL-15) is a recently identified cytokine with biological activities similar to IL-2 (Grabstein et al.,
Science
264:965, 1994). There is approximately 96% nucleotide sequence identity and 96% amino acid sequence identity between human and simian IL-15, and approximately 81% nucleotide sequence identity and 73% amino acid sequence identity between human and murine IL-15.
Northern analysis of a variety of human tissues indicated that IL-15 mRNA is expressed by many human tissues and abundantly by placenta and skeletal muscle. Significant levels of IL-5 mRNA were also observed in other tissues including kidney, lung, liver, and heart. The best sources of IL-15 mRNA so far observed have been adherent mononuclear cells (monocyte enriched, PBM) and epithelial and fibroblast cell lines such as CV-1/EBNA and IMTLH. Activated peripheral blood T cells (PBT), a rich source of IL-2, express no detectable IL-15 mRNA.
IL-15 shares many biological properties with Interleukin-2 (“IL-2”). These properties include proliferation and activation of human and murine T cells and the generation of lymphokine activated killer cells (LAK), natural killer cells (NK) and cytotoxic T lymphocytes (CTL). IL-15 also can co-stimulate with CD40 ligand (CD40L) proliferation and immunoglobulin secretion by B lymphocytes.
In view of the shared biological properties with IL-2, tests were conducted to determine whether IL-15 uses any of the components of the IL-2 receptor. IL-2 cell surface receptors (IL-2R) contain at least three subunits, &agr;, &bgr; and &ggr; (Toshikazu et al.,
Science
, 257: 379 (1992); see also Minami et al.,
Annu. Rev. Immunol
. 11,245, 1993, for a recent review). The &bgr; and &ggr; chains are required for high affinity IL-2 binding and IL-2 signaling and are members of the hematopoietin receptor superfamily. The &agr; chain (or p55) is a low affinity, non-signaling binding subunit, and the only cytokine receptor member of a large family of binding proteins whose members include complement receptor proteins (Perkins et al.,
Biochemistry
27:4004, 1988; Davie et al.,
Cold Spring Harb. Symp. Quant. Biol
. 51:509, 1986). The &ggr; chain of the IL-2R has been shown recently to be shared by receptors for several other cytokines (IL-4, IL-7, IL-9; (Noguchi et al.,
Science
262:1877, 1993; Kondo, et al.,
Science
262:1874, 1993; Kondo et al.,
Science
263:1453, 1994; Russell et al.,
Science
262:1880, 1993; Russell, et al.,
Science
266:1042, 1994) and designated the common &ggr; chain or &ggr;
c
.
Several lines of evidence suggest that there is an IL-15 specific binding protein. For example, an IL-3 dependent murine cell line, 32D (J. S. Greenberger et al.,
Fed. Proc
. 42:2762 (1983)), expressed the complete IL-2R and proliferated in response to IL-2, but cannot bind or respond to IL-15 (Grabstein et al., supra). Similarly, early murine pre-T cells derived from day 13 fetal liver that lack CD3, CD4 and CD8 expression (triple negative, or TN, cells) expressed all three IL-2R subunits, proliferated in response to IL-2, but did not bind or respond to IL-15 (Giri et al.,
EMBO J
. 13:2822, 1994). On the other hand, certain human cell types and cell lines (e.g., umbilical vein endothelial cells, fibroblasts and thymic and stromal cells) did not bind IL-2 but bound IL-15 with high affinity (Giri et al., supra).
Additionally, antibodies directed against the &agr; chain of the IL-2 receptor (anti-IL-2R&agr;) have no effect on IL-15 (Grabstein et al., supra; Giri et al., supra). Antibodies directed against the IL-2R&bgr;, however, are able to block the activity of IL-15, suggesting that IL-15 uses the &bgr; chain of IL-2R. Similarly, some cells require the &ggr; chain of IL-2R for IL-15 signal transduction (Giri et al., supra) IL-15 requires the &bgr; chain of the IL-2R for all the biological activities tested, but the &agr; chain of the IL-2R is not required (Giri et al., supra; Grabstein et al., supra). However, prior to the present invention, neither an IL-15-specific binding protein, nor a DNA encoding such protein, had been isolated.
SUMMARY OF THE INVENTION
The present invention provides isolated Interleukin-15 receptor (IL-15R) and isolated DNA sequences encoding IL-15R, in particular, human and murine IL-15R, or analogs thereof. Preferably, such isolated DNA sequences are selected from the group consisting of (a) DNA sequences comprising a nucleotide sequence derived from the coding region of a native IL-15R gene; (b) DNA sequences capable of hybridization to a DNA of (a) under moderate to high stringency conditions and that encode biologically active IL-15R; and (c) DNA sequences that are degenerate as a result of the genetic code to a DNA sequence defined in (a) or (b) and that encode biologically active IL-15R. The present invention also provides recombinant expression vectors or plasmids and transformed host cells comprising the DNA sequences defined above, recombinant IL-15R proteins produced using the recombinant expression vectors, plasmids or transformed host cells, and processes for producing the recombinant IL-15R proteins utilizing the expression vectors, plasmids or transformed host cells.
The present invention also provides substantially homogeneous preparations of IL-15R protein. The present invention also provides compositions for use in assays for IL-15 or IL-15R, purification of IL-15, or in raising antibodies to IL-15R, comprising effective quantities of the IL-15R proteins of the present invention.
These and other aspects of the present invention will become evident upon reference to the following detailed description.


REFERENCES:
patent: 4925664 (1990-05-01), Jackson et al.
patent: 5194375 (1993-03-01), Park et al.
patent: 5552303 (1996-09-01), Grabstein et al.
patent: 5574138 (1996-11-01), Grabstein et al.
patent: 5785967 (1998-07-01), Gearing et al.
Burgess et al., “Possible Dissociation of the Heparin-binding and Mitogenic Activities of Heparin-binding (Acidic Fibroblast) Growth Factor-1 from Its Receptor-binding Activities by Site-directed Mutagenesis of a Single Lysine Residue,”J. Cell Biol. 111:2129-2138, 1990.
Carson et al., “Interleukin (IL) 15 is a Novel Cytokine That Activates Human Natural Killer Cells Via Components of the IL-2 Receptor,”J. Exp. Med. 180:1395-1403, 1994.
Giri et al., “Biochemical Characterization of a Novel Cytokine IL-15 and its Receptor,”J. Cell Biochem.Supplement, vol. 18D, abstract V561.
Giri et al., “Utilization of the &bgr; and &ggr; chains of the IL-2 receptor by the novel cytokine IL-15,”EMBO J. 13:2822-2830, 1994.
Grabstein et al., “Cloning of a T Cell Growth Factor That Interacts with the &bgr; Chain of the Interleukin-2 Receptor,”Science 264:965-968, 1994.
Greenberger et al., “Interleukin 3-dependent hematopoietic progenitor cell lines,”Fed. Proc. 42:2762-2771, 1983.
Kreitman et al., “Mik-&bgr;1(Fv)-PE40, A Recombinant Immunotoxin Cytotoxic Toward Cells Bearing the &bgr;-Chain of the IL-2 Receptor,”J. Immunol. 149:2810-2815, 1992.
Lazar et al., “Transforming Growth Factor &agr;: Mutation of Aspartic Acid 47 and Leucine 48 Results in Different Biological Activities,”Molecular and Cellular Biol. 8:1247-1252, 1988.
Lindqvist et al., “Expression of Human IL-2 Receptor &agr;- and &bgr;-Chains using the Baculovirus Expression System,”Scand. J. Immunol. 38:267-272, 1993.
Takeshita et al., “Cloning of the &ggr; Chain of the Human IL-2 Receptor,”Science 257:379-382, 1992.
Cosman, D. et al., “Interleukin 15 and its receptor,”Ciba Foundation Symposium 195:221-233, 1995, XP000670929.
Kumaki, S. et al., “Subunits of the interleukin 15 receptor,”J. Cell. Biochem. Suppl. No. 21A:75, Mar. 1995, XP000573660.
Giri, J. G. et al., “IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2,”J. Leukocyte Bio. 57(5):763-766, May 1995, XP000570466.
Anderson, D. M. et al., “Functional characterization of the human interleukin-15 receptor &agr; chain and close

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Interleukin-15 receptors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Interleukin-15 receptors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Interleukin-15 receptors will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3015132

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.