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1. WO1989004838 - RECEPTEURS D'INTERLEUKINE-1

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CLAIMS

1. A DNA sequence consisting essentially of a single open reading frame nucleotide sequence encoding a mammalian IL-1 receptor (IL-1R) or subunit thereof.

2. A DNA sequence according to claim 1, selected from the group consisting of:
(a) cDNA clones having a nucleotide sequence derived from the coding region of a native mammalian IL-1R gene;
(b) DNA sequences capable of hybridization to the clones of (a) under moderately stringent conditions and which encode biologically active IL-1R molecules; and
(c) DNA sequences which are degenerate as a result of the genetic code to the DNA sequences defined in (a) and (b) and which encode biologically active IL-1R molecules.

3. A DNA sequence according to claim 1, consisting essentially of a synthetic gene encoding a mammalian IL-1R or subunit thereof which is capable of being expressed in a recombinant transcriptional unit comprising inducible regulatory elements derived from a microbial or viral operon.

4. A DNA sequence according to claim 3, comprising at least one sequence component derived from a cDNA sequence or copy thereof.

5. A DNA sequence according to claim 1 encoding a truncated IL-1 receptor absent a transmembrane region and cytoplasraic domain.

6. A DNA sequence according to claim 1, which is substantially similar to all or part of the sequence of nucleotides 1-1671 depicted in Tables 2A-2C.

7. A DNA sequence according to claim 1, which is substantially similar to all or part of the sequence of nucleotides 1-1656 depicted in Tables 4A-4C.

8. A recombinant expression vector comprising a DNA sequence according to any of claims 1-7.

9. A process for preparing a mammalian IL-1R or an analog thereof, comprising culturing a suitable host cell comprising a vector according to claim 8 under conditions promoting expression.

10. A population of eukaryotic cells which express more than 30,000 surface IL-1 receptors per cell.

11. A population of eukaryotic cells according to claim 10, which express more than 45,000 surface IL-1 receptors per cell.

12. A homogeneous biologically active mammalian IL-1R
composition.

13. A homogeneous biologically active mammalian IL-1R
composition according to claim 12, consisting essentially of murine IL-1R.

14. A homogeneous biologically active mammalian IL-1R
composition according to claim 12, consisting essentially of human IL-1R.

15. A protein composition comprising a soluble mammalian IL-1R, IL-1R subunit, or substantially similar or identical IL-1R analog produced by recombinant cell culture and having a specific binding activity of at least about 0.01 nanomole IL-1/nanomole IL-1R.

16. A composition according to claim 15, wherein the IL-1R composition comprises an amino acid sequence which is substantially similar to all or part of the amino acid sequence of residues 1-557 in Tables 2A-2C.

17. A composition according to claim 15, wherein the IL-1R composition comprises an amino acid sequence which is substantially similar to all or part of the amino acid sequence of residues 1-552 in Tables 4A-4C.

18. A composition according to claim 15, consisting essentially of a substantially homogeneous protein composition comprising murine IL-1 receptor in the form of a glycoprotein having a molecular weight of about 82,000 daltons by SDS-PAGE, a binding affinity (Ka) for human IL-1α of from 3-6 x 109 M, and the N-terminal amino acid sequence NH2-Leu-Glu-Ile-Asp-Val-Cys-Thr-Glu-Tyr-Pro-Asn-Gln-He-Val-Leu-Phe-Leu-Ser-Val-Asn-Glu-Ile-Asp-He-Arg-Lys.

19. A mammalian IL-1 receptor for use in human or veterinary medicine.

20. The use of IL-1 receptor in preparing a medicament for regulating immune or inflammatory responses in a mammal.

21. The use of claim 20, wherein the IL-1 receptor is human IL-1 receptor and the mammal to be treated is a human.

22. A composition according to claim 12 absent a transmembrane region and cytoplasmic domain.

23. A pharmaceutical composition suitable for parenteral administration to a human patient for regulating immune or
inflammatory responses in mammals, comprising an effective amount of a human IL-1 receptor or biologically active human IL-1 receptor analog or subunit in admixture with a suitable diluent or carrier.

24. A process, for purifying a mammalian IL-1 receptor,
comprising:
(a) applying a sample comprising mammalian IL-1 receptor to an affinity matrix comprising an IL-1 or antibody molecule bound to an insoluble support; and
(b) eluting the IL-1 receptor from the affinity matrix.

25. A process according to claim 24, further comprising the steps of:
(c) applying the partially purified murine IL-1 receptor to a lectin affinity column;
(d) eluting the murine IL-1 receptor from the lectin column; and

(e) treating the partially purified murine IL-1 receptor by reversed phase high performance liquid chromatography and eluting therefrom murine IL-1 receptor as a single peak of absorbance at 280 nanometers which, when analyzed by SDS-PAGE and silver staining, appears as a single band.

26. A process according to claim 24, wherein the IL-1 molecule is recombinant human IL-1α.

27. A method for detecting IL-1 or IL-1 receptor molecules or the interaction thereof, comprising use of a protein composition according to claim 15.

28. Antibodies immunoreactive with IL-1 receptor.