Title:
HUMAN ELASTASE I
Document Type and Number:
WIPO Patent Application WO/2000/061728
Kind Code:
A2
Abstract:
The present invention provides an isolated or recombinant polynucleotide which comprises a nucleic acid sequence encoding a mutant of human elastase I. The mutant elastase I has a frame shift mutation in any one of codons (207 to 225), preferably codon (208) and may be a contributory factor in hyperproliferative skin diseases, such as psoriasis, eczema, lupus erythmatosus, erythema, and possibly cancer.
Inventors:
GERST-TALAS ULVI (GB)
DUNLOP JOHN (ES)
KELSELL DAVID PETER (GB)
DUNLOP JOHN (ES)
KELSELL DAVID PETER (GB)
Application Number:
PCT/GB2000/001389
Publication Date:
October 19, 2000
Filing Date:
April 12, 2000
Export Citation:
Assignee:
QUEEN MARY & WESTFIELD COLLEGE (GB)
GERST TALAS ULVI (GB)
DUNLOP JOHN (ES)
KELSELL DAVID PETER (GB)
GERST TALAS ULVI (GB)
DUNLOP JOHN (ES)
KELSELL DAVID PETER (GB)
International Classes:
G01N33/573; C07K16/40; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N9/50; C12N9/64; C12N15/09; C12P21/08; C12Q1/68; G01N33/574; (IPC1-7): C12N9/00
Domestic Patent References:
| WO1998014616A1 | 1998-04-09 | |||
| WO1997012992A2 | 1997-04-10 |
Foreign References:
| EP0157604A2 | 1985-10-09 | |||
| EP0244189A2 | 1987-11-04 | |||
| DE4107765A1 | 1992-01-30 |
Other References:
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 7 October 1997 (1997-10-07), XP002148780 HINXTON, GB
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 25 May 1992 (1992-05-25), XP002148781 HINXTON, GB cited in the application -& KAWASHIMA ET AL., : "Genomic organization of the human homologue of the rat pancreatic elastase I gene" DNA SEQ., vol. 2, 1992, pages 303-312, XP000949959 cited in the application
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 8 January 1998 (1998-01-08), XP002148782 HINXTON, GB
DATABASE WPI Section Ch, Week 199018 Derwent Publications Ltd., London, GB; Class B04, AN 1990-137116 XP002148784 & JP 02 086777 A (SANKYO CO LTD), 27 March 1990 (1990-03-27)
DATABASE WPI Section Ch, Week 198544 Derwent Publications Ltd., London, GB; Class B04, AN 1985-273645 XP002148785 & JP 60 186284 A (KIRIN BREWERY KK), 21 September 1985 (1985-09-21)
ROSE SCOTT D ET AL: "Evolutionary silencing of the human elastase I gene (ELA1)." HUMAN MOLECULAR GENETICS, vol. 6, no. 6, 1997, pages 897-903, XP000946577 ISSN: 0964-6906 cited in the application
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 19 March 1992 (1992-03-19), XP002148783 HINXTON, GB cited in the application
WIEDOW O ET AL: "ELAFIN: AN ELASTASE-SPECIFIC INHIBITOR OF HUMAN SKIN. ÖPURIFICATION, CHARACTERIZATION, AND COMPLETE AMINO ACID SEQUENCE*" JOURNAL OF BIOLOGICAL CHEMISTRY,US,AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, vol. 265, no. 25, 5 September 1990 (1990-09-05), pages 14791-14795, XP000142451 ISSN: 0021-9258 cited in the application
TSUNEMI M ET AL: "SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF ELAFIN, AN ELEASTASE-SPECIFIC INHIBITOR" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,US,ACADEMIC PRESS INC. ORLANDO, FL, vol. 185, no. 3, 30 June 1992 (1992-06-30), pages 967-973, XP000619381 ISSN: 0006-291X
TALAS ULVI ET AL: "Human elastase 1: Evidence for expression in the skin and the identification of a frequent frameshift polymorphism." JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 114, no. 1, January 2000 (2000-01), pages 165-170, XP000949997 ISSN: 0022-202X
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 25 May 1992 (1992-05-25), XP002148781 HINXTON, GB cited in the application -& KAWASHIMA ET AL., : "Genomic organization of the human homologue of the rat pancreatic elastase I gene" DNA SEQ., vol. 2, 1992, pages 303-312, XP000949959 cited in the application
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 8 January 1998 (1998-01-08), XP002148782 HINXTON, GB
DATABASE WPI Section Ch, Week 199018 Derwent Publications Ltd., London, GB; Class B04, AN 1990-137116 XP002148784 & JP 02 086777 A (SANKYO CO LTD), 27 March 1990 (1990-03-27)
DATABASE WPI Section Ch, Week 198544 Derwent Publications Ltd., London, GB; Class B04, AN 1985-273645 XP002148785 & JP 60 186284 A (KIRIN BREWERY KK), 21 September 1985 (1985-09-21)
ROSE SCOTT D ET AL: "Evolutionary silencing of the human elastase I gene (ELA1)." HUMAN MOLECULAR GENETICS, vol. 6, no. 6, 1997, pages 897-903, XP000946577 ISSN: 0964-6906 cited in the application
DATABASE EMBL NUCLEOTIDE AND PROTEIN SEQUENCES, 19 March 1992 (1992-03-19), XP002148783 HINXTON, GB cited in the application
WIEDOW O ET AL: "ELAFIN: AN ELASTASE-SPECIFIC INHIBITOR OF HUMAN SKIN. ÖPURIFICATION, CHARACTERIZATION, AND COMPLETE AMINO ACID SEQUENCE*" JOURNAL OF BIOLOGICAL CHEMISTRY,US,AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, vol. 265, no. 25, 5 September 1990 (1990-09-05), pages 14791-14795, XP000142451 ISSN: 0021-9258 cited in the application
TSUNEMI M ET AL: "SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF ELAFIN, AN ELEASTASE-SPECIFIC INHIBITOR" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,US,ACADEMIC PRESS INC. ORLANDO, FL, vol. 185, no. 3, 30 June 1992 (1992-06-30), pages 967-973, XP000619381 ISSN: 0006-291X
TALAS ULVI ET AL: "Human elastase 1: Evidence for expression in the skin and the identification of a frequent frameshift polymorphism." JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 114, no. 1, January 2000 (2000-01), pages 165-170, XP000949997 ISSN: 0022-202X
Attorney, Agent or Firm:
Lee, Nicholas John (Kilburn & Strode 20 Red Lion Street London
WC1R 4PJ, GB)
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Claims:
Claims:
| 1. | An isolated or recombinant polynucleotide comprising a nucleic acid sequence encoding a mutant of human elastase I, the nucleic acid sequence comprising the sequence of Figure 3 with a frame shift mutation in any one of codons 207 to 225. |
| 2. | A polynucleotide as claimed in claim 1, wherein the frame shift mutation is a single base insertion in codon 208. |
| 3. | A polynucleotide as claimed in claim 1 or claim 2, wherein the single base inserted is a cytosine nucleotide. |
| 4. | An isolated polypeptide comprising a mutant of human elastase I which comprises the amino acid sequence shown in Figure 6A (ELA1 var) or has substantial sequence identity with that sequence. |
| 5. | A method of determining the predisposition of a subject to a hyperproliferative skin condition or cancer, the method comprising detecting in the subject the presence of an allele of ELA1, wherein said allele encodes a mutant of human elastase I and has a frame shift mutation in any one of codons 207 to 225 of the nucleic acid sequence of Figure 3. |
| 6. | A method as claimed in claim 5, wherein the frame shift mutation is a single base insertion in codon 208. |
| 7. | A method as claimed in claim 6, wherein the single base inserted is a cytosine nucleotide. |
| 8. | A method as claimed in claim 5,6 or 7, wherein the allele is detected by sequencing a genomic DNA segment from chromosome 12ql3 of the subject. |
| 9. | A method as claimed in claim 5,6 or 7, wherein the allele is detected by (i) mixing a nucleic acid sample from the subject with one or more polynucleotide probes capable of hybridising selectively to an ELA1 allele in a reaction and. (ii) monitoring the reaction to determine the presence of the gene allele acid in the sample, thereby indicating whether the subject is at risk for a hyperproliferative skin condition or cancer. |
| 10. | A method as claimed in claim 5,6 or 7, wherein detection of the allele comprises (i) mixing in an immunological assay a human elastase I protein sample from the subject with an antibody reagent specific for the allele and (ii) monitoring the assay to determine specific binding between the antibody reagent and the protein sample, thereby indicating whether the subject is at risk for a hyperproliferative skin condition or cancer. |
| 11. | A method as claimed in claim 10, wherein the antibody reagent is a monoclonal antibody specifically reactive with an antigenic determinant specific for an allele. |
| 12. | A method as claimed in claim 11, wherein the antibody reagent is a monoclonal antibody specifically reactive with the polypeptide as claimed in claim 4. |
| 13. | A monoclonal antibody specifically reactive with the polypeptide as claimed in claim 4. |
| 14. | A vector comprising a polynucleotide as claimed in claim 1,2 or 3. |
| 15. | A host comprising a vector as claimed in claim 14.. |
| 16. | A method for obtaining a polypeptide as claimed in claim 4, comprising incubating a host as claimed in claim 15 under conditions causing expression of the polypeptide and then purifying the polypeptide. |
Description:
INTERNATIONAL SEARCH REPORT Inter mal ApplicationNo PCT/GB00/01389 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT CategoryCitationofdocument,withindication,whereappropriate,o
ftherelevantpassagesRelevanttoclaimNo. XDATABASEEMBLNUCLEOTIDEANDPROTEIN 1 SEQUENCES, 25May1992(1992-05-25),XP002148781 HINXTON,GB citedintheapplication AC=X62252. H.sapiensexon3forelastaseI;serine protease. abstract X-& KAWASHIMA ET AL., :"Genomic1-9 organizationofthehumanhomologueofthe ratpancreaticelastaseIgene" DNASEQ., vol.2,1992,pages303-312,XP000949959 citedintheapplication thewholedocument XDATABASEEMBLNUCLEOTIDEANDPROTEIN1 SEQUENCES, 8January1998(1998-01-08),XP002148782 HINXTON,GB ACX91400.MacacafascicularismRNAfor elastaseI;elalgene abstract XDATABASEWPI 1 SectionCh,Week199018 DerwentPublicationsLtd.,London,GB; ClassB04,AN1990-137116 XP002148784 &JP02086777A(SANKYOCOLTD), 27March1990(1990-03-27) abstract XEP0157604A(SANKYOCO)4,16 9October1985(1985-10-09) thewholedocument XEP0244189A(SANKYOCO)4,16 4November1987(1987-11-04) thewholedocument XDATABASEWPI4,16 SectionCh,Week198544 DerwentPublicationsLtd.,London,GB; ClassB04,AN1985-273645 XP002148785 &JP60186284A(KIRINBREWERYKK), 21September1985(1985-09-21) abstract AWO9814616A(PERSEPTIVEBIOSYSTEMSINC)5-9 9April1998(1998-04-09) citedintheapplication thewholedocument ___ INTERNATIONALSEARCHREPORT Inter lnal ApplicatlonNo PCT/GB00/01389 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category ° Citationotdocument,withindication,whereappropriate,oftherele
vantpassagesRelevanttoclaimNo. AWO9712992A(STATEUNIVERSITYOFUTRECHT5-9 ;UNIVERASMUS(NL);ROYALNETHERLANDS) 10April1997(1997-04-10) page5,line1-18 page27,line1-page35,line6 ADE4107765A(SCHEBOTECHMEDIZINISCH10-13 BIOLOG)30January1992(1992-01-30) thewholedocument AROSESCOTTDETAL:"Evolutionary1-9 silencingofthehumanelastaseIgene (ELA1)." HUMANMOLECULARGENETICS, vol.6,no.6,1997,pages897-903, XP000946577 ISSN:0964-6906 citedintheapplication thewholedocument ADATABASEEMBLNUCLEOTIDEANDPROTEIN 1 SEQUENCES, 19March1992(1992-03-19),XP002148783 HINXTON,GB citedintheapplication AC=D00159.Homosapiensgenefor pancreaticelastaseI,partialcds. abstract AWIEDOW0ETAL: "ELAFIN:AN 1 ELASTASE-SPECIFICINHIBITOROFHUMANSKIN. \PURIFICATION,CHARACTERIZATION,AND COMPLETEAMINOACIDSEQUENCE*" JOURNALOFBIOLOGICAL CHEMISTRY,US,AMERICANSOCIETYOF BIOLOGICALCHEMISTS,BALTIMORE,MD, vol.265,no.25, 5September1990(1990-09-05),pages 14791-14795,XP000142451 ISSN:0021-9258 citedintheapplication thewholedocument ATSUNEMIMETAL: "SYNTHESISAND 1 STRUCTURE-ACTIVITYRELATIONSHIPSOF ELAFIN,ANELEASTASE-SPECIFICINHIBITOR" BIOCHEMICALANDBIOPHYSICALRESEARCH COMMUNICATIONS,US,ACADEMICPRESSINC. ORLANDO,FL, vol.185,no.3, 30June1992(1992-06-30),pages967-973, XP000619381 ISSN:0006-291X thewholedocument -/-- 1 INTERNATIONALSEARCHREPORT Interrnal Application No r PCT/GB00/01389 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category'Citationofdocument,withindication,whereappropnate,o
ftherelevantpassagesRelevanttoclaim No. P,XTALASULVIETAL:"Humanelastase1:1-16 Evidenceforexpressionintheskinand theidentificationofafrequent frameshiftpolymorphism." JOURNALOFINVESTIGATIVEDERMATOLOGY, vol.114,no.1,January2000(2000-01), pages165-170,XP000949997 ISSN:0022-202X thewholedocument 1 INTERNATIONALSEARCHREPORT i-------------------) internai ApplicationNo ..fottnation on patentfamily members PCT/GB 00/01389 PatentdocumentPublication Patent family Publication citedinsearchreportdatemember(s)date JP2086777A27-03-1990NONE EP0157604A09-10-1985JP60207583A 19-10-1985 AT84071T 15-01-1993 DE3586926A 11-02-1993 DE3586926T 22-07-1993 EP0244189A04-11-1987JP1942558C 23-06-1995 JP6073456B 21-09-1994 JP62253381A 05-11-1987 AT93540T 15-09-1993 CA1299508A 28-04-1992 DE3787112D 30-09-1993 DE3787112T 07-04-1994 ES2059371T 16-11-1994 KR9512972B 24-10-1995 US4968614A 06-11-1990 US5162205A 10-11-1992 JP60186284A21-09-1985NONE WO9814616A09-04-1998US5885775A 23-03-1999 EP0931166A 28-07-1999 WO9712992A10-04-1997AU7142796A 28-04-1997 US5958684A 28-09-1999 DE4107765A30-01-1992AT128734T 15-10-1995 AU646476B 24-02-1994 AU8100291A 02-03-1992 CA2088354A 29-01-1992 WO9202630A 20-02-1992 DE59106634D 09-11-1995 DK547059T 19-02-1996 EP0547059A 23-06-1993 ES2080955T 16-02-1996 GR3018483T 31-03-1996 JP10080272A 31-03-1998 US5622837A 22-04-1997