Title:
MOLECULES DERIVED FROM INTERLEUKIN-1 BETA
Document Type and Number:
WIPO Patent Application WO/2001/005822
Kind Code:
A2
Abstract:
The present invention relates to an isolated C-terminal fragment of pro-interleukin 1$g(b) comprising a protein sequence having a molecular weight of 20-22 kD or an N-terminal truncation thereof, incorporating an interleukin-1$g(b) converting enzyme (ICE) cleavage site, the fragment being cleavable by ICE to produce active IL-1$g(b), and the cleavage product thereof.
Inventors:
TOULMOND SYLVIE (CA)
Application Number:
PCT/GB2000/002657
Publication Date:
January 25, 2001
Filing Date:
July 11, 2000
Assignee:
UNIV MANCHESTER (GB)
TOULMOND SYLVIE (CA)
International Classes:
C07K14/545; (IPC1-7): C07K14/00
Domestic Patent References:
Foreign References:
| EP0237967A2 | 1987-09-23 | | | |
| EP0187991A2 | 1986-07-23 | | | |
Other References:
PERREGAUX DAVID G ET AL: "Human monocyte stimulus-coupled IL-1beta posttranslational processing: Modulation via monovalent cations." AMERICAN JOURNAL OF PHYSIOLOGY, vol. 275, no. 6 PART 1, December 1998 (1998-12), pages C1538-C1547, XP002160115 ISSN: 0002-9513 cited in the application
AURON P E ET AL: "STUDIES ON THE MOLECULAR NATURE OF HUMAN INTERLEUKIN 1" JOURNAL OF IMMUNOLOGY, vol. 138, no. 5, 1987, pages 1447-1456, XP002160116 ISSN: 0022-1767 cited in the application
BLACK R A ET AL: "GENERATION OF BIOLOGICALLY ACTIVE INTERLEUKIN-1-BETA BY PROTEOLYTIC CLEAVAGE OF THE INACTIVE PRECURSOR" JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 263, no. 19, 1988, pages 9437-9442, XP002160117 ISSN: 0021-9258
HIGGINS GLORIA C ET AL: "Interleukin 1-beta propeptide is detected by intracellularly and extracellularly when human monocytes are stimulated with LPS in vitro." JOURNAL OF EXPERIMENTAL MEDICINE, vol. 180, no. 2, 1994, pages 607-614, XP000982152 ISSN: 0022-1007
LUNDQVIST ELISABET NYLANDER ET AL: "Biologically active, alternatively processed interleukin-1-beta in psoriatic scales." EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 27, no. 9, 1997, pages 2165-2171, XP000982123 ISSN: 0014-2980 cited in the application
PECCEU F ET AL: "Human interleukin 1-beta fused to the human growth hormone signal peptide is N-glycosylated and secreted by Chinese hamster ovary cells" GENE,ELSEVIER BIOMEDICAL PRESS. AMSTERDAM,NL, vol. 97, 1991, pages 253-258, XP002131134 ISSN: 0378-1119
PATENT ABSTRACTS OF JAPAN vol. 012, no. 128 (C-489), 20 April 1988 (1988-04-20) -& JP 62 248489 A (AJINOMOTO CO INC), 29 October 1987 (1987-10-29)
Attorney, Agent or Firm:
Stark, Amanda Jane (Marks & Clerk Sussex House 83-85 Mosley
Street Manchester M2 3LG, GB)
Claims:
CLAIMS:
| 1. |
An isolated Cterminal fragment of prointerleukin I P comprising a protein sequence having a molecular weight of 2022 kD or an Nterminal truncation thereof, incorporating an interleukinlp converting enzyme (ICE) cleavage site, the fragment being cleavable by ICE to produce active IL1 (3. |
| 2. |
An isolated fragment according to claim 1 from a mammalian source. |
| 3. |
An isolated fragment according to claim 2 from a rodent or human source. |
| 4. |
An isolated fragment according to claim 2 from rat. |
| 5. |
An isolated fragment according to claim 1 comprising a protein sequence having at least 80% identity over its entire length to the amino acid sequence of SEQ ID No. 1. |
| 6. |
An isolated fragment according to claim 5 comprising a protein sequence having at least 80% identity over their entire length to any one of SEQ ID Nos. |
| 8. |
An isolated fragment according to claim 1 comprising a protein sequence having at least 90% identity with one of the amino acid sequences shown as SED ID Nos. 111 over its entire length. |
| 9. |
An isolated fragment according to claim 7 comprising a protein sequence having at least 95% identity with one of the amino acid sequences shown as SED ID Nos. 111 over its entire length. |
| 10. |
An isolated fragment according to claim 8 comprising a protein sequence having at least 97,98,99 or 100% sequence identity with one of the amino acid sequences shown as SEQ ID Nos. 111. |
| 11. |
An isolated fragment according to any preceding claim comprising a protein sequence variant of one of the amino acid sequences shown as SEQ ID Nos. 1 11 as herein before defined. |
| 12. |
An isolated fragment according to any preceding claim which is phosphorylated at one, two, three or four consensus casein kinase II phosphorylation sites. |
| 13. |
An isolated nucleic acid molecule encoding the isolated fragment of any one of claims 1 to 11. |
| 14. |
A vector comprising the nucleic acid molecule of claim 12. |
| 15. |
A host cell transformed with the nucleic acid molecule of claim 12 or the vector of claim 13. |
| 16. |
Production of the isolated fragment according to any one of claims 1 to 11 by culturing the cells according to claim 14. |
| 17. |
Antibodies raised against the isolated fragment according to any one of claims 1 to 11. |
| 18. |
Use of the isolated fragment according to any one of claims 1 to 11, the nucleic acid molecule of claim 12, vectors according to claim 13, host cells according to claim 14 or antibodies according to claim 16 for research, therapy or diagnosis. |
| 19. |
Use of the isolated fragment according to any one of claims 1 to 11, the nucleic acid molecule of claim 12, vectors according to claim 13, host cells according to claim 14 or antibodies according to claim 16 in diagnosis and therapy of conditions involving either an excess or a deficiency in IL1 (3. |
| 20. |
An isolated peptide which is the minor fragment produced by cleavage of the 2022 kD protein according to any one of claims 1 to 11 with ICE. |
| 21. |
An isolated peptide according to claim 19 of 40 to 25 amino acid residues in length. |
| 22. |
An isolated peptide according to claim 20 of 30 to 25 amino acid residues in length. |
| 23. |
An isolated peptide according to claim 19 having at least 80 % identity to any one of the sequences shown as SEQ ID Nos. 12 to 22 over its entire length. |
| 24. |
An isolated peptide according to claim 22 having at least 90% identity to any one of the amino acid sequences shown as SED ID Nos. 1222 over its entire length. |
| 25. |
An isolated peptide according to claim 23 having at least 95% identity with one of the amino acid sequences shown as SED ID Nos. 1222 over its entire length. |
| 26. |
An isolated peptide according to claim 24 having at least 97,98,99 or 100% sequence identity with one of the amino acid sequences shown as SEQ ID Nos. 1222 over its entire length. |
| 27. |
An isolated peptide according to claim 19 comprising a peptide sequence variant of one of the amino acid sequences shown as SEQ ID Nos. 1222 as herein before defined. |
| 28. |
An isolated peptide according to any one of claims 19 to 26 which is phosphorylated at one or two consensus casein kinase II phosphorylation sites. |
| 29. |
An isolated nucleic acid molecule encoding the isolated peptide of any one of claims 19 to 27. |
| 30. |
A vector comprising the nucleic acid molecule of claim 28. |
| 31. |
A host cell transformed with the nucleic acid molecule of claim 28 or the vector of claim 29. |
| 32. |
Production of the isolated peptide according to any one of claims 19 to 27 by culturing the cells according to claim 30. |
| 33. |
Antibodies raised against the isolated peptide according to any one of claims 19 to 27. |
| 34. |
Use of the isolated peptide according to any one of claims 19 to 27, the nucleic acid molecule of claim 28, the vector according to claim 29, host cells according to claim 30 or antibodies according to claim 32 for research, therapy or diagnosis. |
| 35. |
Use of the isolated peptide according to any one of claims 19 to 27, the nucleic acid molecule of claim 28, the vector according to claim 29, host cells according to claim 30 or antibodies according to claim 32 for diagnosis and therapy of conditions involving either an excess or a deficiency in IL1 (3. |
Description:
INTERNATIONAL SEARCH REPORT Inte ional Application No PCT/GB 00/02657 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. X EP 0 187 991 A (OTSUKA PHARMA CO LTD) 1-3, 23 July 1986 (1986-07-23) 10-15, 17,18, 28-30 * two N-terminally extended forms of human IL-lbeta, as well as full-length pIL-lbeta * peptides II and III page 5-page 6 X PERREGAUX DAVID G ET AL:"Human monocyte 1-3, stimulus-coupled IL-lbeta 10-16,32 posttranslational processing: Modulation via monovalent cations." AMERICAN JOURNAL OF PHYSIOLOGY, vol. 275, no. 6 PART 1, December 1998 (1998-12), pages C1538-C1547, XP002160115 ISSN: 0002-9513 cited in the application * 20 kDa protein, immunoprecipitated with anti-IL-lbeta antibody * page C1540, right-hand column, paragraph 1; figures 1,2,5A X AURON P E ET AL:"STUDIES ON THE 1-3, MOLECULAR NATURE OF HUMAN INTERLEUKIN 1"10-16,32 JOURNAL OF IMMUNOLOGY, vol. 138, no. 5,1987, pages 1447-1456, XP002160116 ISSN: 0022-1767 cited in the application * immunoprecipitated IL-1 forms of 23 and 18 kD * the whole document X BLACK R A ET AL:"GENERATION OF 1-3, BIOLOGICALLY ACTIVE INTERLEUKIN-1-BETA BY 10-17,32 PROTEOLYTIC CLEAVAGE OF THE INACTIVE PRECURSOR" JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 263, no. 19,1988, pages 9437-9442, XP002160117 ISSN: 0021-9258 * IL-lbeta cleaved by trypsin, chymotrypsin, elastin and S. aureus protease, resulting in cleavage after residues 75/76,113,103 and 111, respectively; all are biologically active * abstract; figure 5 6 6 INTERNATIONAL SEARCH REPORT Inte ional Application No PCT/GB00/02657 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. X HIGGINS GLORIA C ET AL:"Interleukin 32-34 1-beta propeptide is detected by intracellularly and extracellularly when human monocytes are stimulated with LPS in vitro." JOURNAL OF EXPERIMENTAL MEDICINE, vol. 180, no. 2,1994, pages 607-614, XP000982152 ISSN: 0022-1007 * antibody specific for the propeptide fragment with amino acids 2-116, the isolated propeptide fragment, and uses therof * the whole document X LUNDQVIST ELISABET NYLANDER ET AL: 1-3, "Biologically active, alternatively 10-16,32 processed interleukin-1-beta in psoriatic scales." EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 27, no. 9,1997, pages 2165-2171, XP000982123 ISSN: 0014-2980 cited in the application * slightly longer psoriasis form of processed* the whole document A PECCEU F ET AL:"Human interleukin 1-beta fused to the human growth hormone signal peptide is N-glycosylated and secreted by Chinese hamster ovary cells" GENE, ELSEVIER BIOMEDICAL PRESS. AMSTERDAM, NL, vol. 97,1991, pages 253-258, XP002131134 ISSN: 0378-1119 * fusion between hGH signal peptide and mature hIL-lbeta is processed to a mature N-glycosylated form of 22 kD, but not by ICE * the whole document A PATENT ABSTRACTS OF JAPAN vol. 012, no. 128 (C-489), 20 April 1988 (1988-04-20) -& JP 62 248489 A (AJINOMOTO CO INC), 29 October 1987 (1987-10-29) * Introduction of kallikrein cleavage site N-terminal to a mature IL-lbeta protein, expression, cleavage and mature * page 574, left-hand column, paragraph 4 -page 576 6 INTERNATIONAL SEARCH REPORT Inte ional Application No Information on patent family members PCT/GB 00/02657 PCT/GB 00/02657 Patent document Publication Patent cited in search report date member (s) date EP 0237967 A 23-09-1987 AU 595864 B 12-04-1990 AU 6993387 A 08-09-1988 DE 3750432 D 06-10-1994 DE 3750432 T 20-04-1995 DE 3751593 D 21-12-1995 DE 3751593 T 28-03-1996 DK 51493 A 05-05-1993 DK 127787 A 15-09-1987 DK 127887 A 15-09-1987 EP 0237073 A 16-09-1987 EP 0569042 A 10-11-1993 EP 0578278 A 12-01-1994 ES 2009215 A 16-09-1989 ES 2009216 A 16-09-1989 HK 1003115 A 09-10-1998 JP 2591615 B 19-03-1997 JP 63152398 A 24-06-1988 JP 2572220 B 16-01-1997 JP 63164899 A 08-07-1988 JP 10072365 A 17-03-1998 JP 2608023 B 07-05-1997 JP 6172395 A 21-06-1994 JP 9118633 A 06-05-1997 JP 2711430 B 10-02-1998 JP 6220093 A 09-08-1994 JP 6219964 A 09-08-1994 JP 2753694 B 20-05-1998 JP 8225596 A 03-09-1996 JP 2753695 B 20-05-1998 JP 8253422 A 01-10-1996 KR 9500886 B 03-02-1995 US 5008374 A 16-04-1991 US 6107465 A 22-08-2000 US 5543140 A 06-08-1996 US 5702698 A 30-12-1997 US 5847098 A 08-12-1998 US 5342614 A 30-08-1994 US 5342615 A 30-08-1994 US 5371204 A 06-12-1994 WO 8810299 A 29-12-1988 DK 177488 A 01-10-1989 AU 1987088 A 19-01-1989 DK 652889 A 21-12-1989 EP 0371041 A 06-06-1990 JP 3503596 T 15-08-1991 NO 895154 A 20-12-1989 EP 0187991 A 23-07-1986 JP 62142121 A 25-06-1987 DE 3586050 D 17-06-1992 DE 187991 T 30-04-1987 DK 586685 A 22-06-1986 ES 551055 D 16-03-1988 ES 8801944 A 16-05-1988 ES 557623 D 16-07-1988 ES 8802539 A 16-10-1988 JP 2583753 B 19-02-1997 JP 62174022 A 30-07-1987 JP 2721854 B 04-03-1998 INTERNATIONAL SEARCH REPORT Inte. onal Application No Information on patent family members PCT/GB 00/02657 PCT/GB 00/02657 Patent document Publication Patent family Publication cited in search report date member (s) date EP 0187991 A JP 8245695 A 24-09-1996 KR 9312106 B 24-12-1993 MX 9203748 A 30-09-1992 US 6107465 A 22-08-2000 US 5847098 A 08-12-1998 US 5342614 A 30-08-1994 US 4898818 A 06-02-1990 JP 62248489 A 29-10-1987 NONE
