Title:
NOVEL METHOD FOR IDENTIFYING ANTIBACTERIAL COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2000/061793
Kind Code:
A2
Abstract:
The present invention relates to a method for identifying an antagonist or inhibitor of the expression of a gene encoding a polypeptide essential for bacterial growth or survival as well as for an antagonist or inhibitor of said polypeptide. The invention further relates to a method for improved antagonists or inhibitors. The invention also provides an antagonist or inhibitor of the activity of said polypeptide. The invention is further related to a method for producing a therapeutic agent in a composition comprising said antagonist or inhibitor. Furthermore, the invention is related to the use of the polypeptide and the antagonist or inhibitor as well as to a method to identify a surrogate marker.
Inventors:
LOFERER HANNES (DE)
JACOBI ALEXANDER (DE)
JACOBI ALEXANDER (DE)
Application Number:
PCT/EP2000/003135
Publication Date:
October 19, 2000
Filing Date:
April 07, 2000
Export Citation:
Assignee:
GPC BIOTECH AG (DE)
LOFERER HANNES (DE)
JACOBI ALEXANDER (DE)
LOFERER HANNES (DE)
JACOBI ALEXANDER (DE)
International Classes:
A61K38/00; G01N33/50; A61K45/00; A61P31/04; C07K14/245; C12N15/09; C12Q1/02; C12Q1/18; C12Q1/68; G01N33/15; (IPC1-7): C12Q1/18
Domestic Patent References:
| WO1998042875A1 | 1998-10-01 | |||
| WO1999047553A2 | 1999-09-23 | |||
| WO1995009925A1 | 1995-04-13 | |||
| WO1996035804A1 | 1996-11-14 | |||
| WO1998035054A1 | 1998-08-13 | |||
| WO1999014311A1 | 1999-03-25 |
Other References:
MOIR, D.T. ET AL.: "Genomics and Antimicrobial Drug Discovery" ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 43, no. 3, March 1999 (1999-03), pages 439-446, XP000921053
ARIGONI F ET AL: "A genome-based approach for the identification of essential bacterial genes" NATURE BIOTECHNOLOGY,US,NATURE PUBLISHING, vol. 16, no. 16, September 1998 (1998-09), pages 851-856-856, XP002124132 ISSN: 1087-0156
BALTZ ET AL: "DNA sequence sampling of the Streptococcus pneumoniae genome to identify novel targets for antibiotic development" MICROBIAL DRUG RESISTANCE,US,LIEBERT, vol. 4, no. 1, 21 March 1998 (1998-03-21), pages 1-9-9, XP002112153 ISSN: 1076-6294
TRIAS AND GORDON: "INNOVATIVE APPROACHES TO NOVEL ANTIBACTERIAL DRUG DISCOVERY" CURRENT OPINION IN BIOTECHNOLOGY,GB,LONDON, vol. 8, no. 8, 1997, pages 757-762-762, XP002119418 ISSN: 0958-1669
TATUSOV R L ET AL: "METABOLISM AND EVOLUTION OF HAEMOPHILUS INFLUENZAE DEDUCED FROM A WHOLE-GENOME COMPARISON WITH ESCHERICHIA COLI" CURRENT BIOLOGY,GB,CURRENT SCIENCE,, vol. 6, no. 3, 1 March 1996 (1996-03-01), pages 279-291-291, XP000857871 ISSN: 0960-9822
FLEISCHMANN R D ET AL: "WHOLE-GENOME RANDOM SEQUENCING AND ASSEMBLY OF HAEMOPHILUS INFLUENZAE RD" SCIENCE,US,AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, vol. 269, no. 5223, 28 July 1995 (1995-07-28), pages 496-498,507-51, XP000517090 ISSN: 0036-8075
ROHDICH, F. ET AL.: "Cytidine 5'-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol" PNAS, vol. 96, no. 21, 12 October 1999 (1999-10-12), pages 11758-11763, XP002132607
POST D A ET AL: "CHARACTERIZATION OF THE HEMA-PRS REGION OF THE ESCHERICHIA COLI ANDSALMONELLA TYPHIMURIUM CHROMOSOMES: IDENTIFICATION OF TWO OPEN READING FRAMES AND IMPLICATIONS FOR PRS EXPRESSION" JOURNAL OF GENERAL MICROBIOLOGY,GB,SOCIETY FOR MICROBIOLOGY, READING, vol. 139, no. 2, 1993, pages 259-266, XP000923112 ISSN: 0022-1287
GREEN J M ET AL: "CHARACTERIZATION AND SEQUENCE OF ESCHICHIA COLI PABC, THE GENE ENCODING AMINODEOXYCHORISMATE LYASE, A PYRIDOXAL PHOSPHATE-CONTAINING ENZYME" JOURNAL OF BACTERIOLOGY,WASHINGTON, DC,US, vol. 174, no. 16, August 1992 (1992-08), pages 5317-5323, XP000952311 ISSN: 0021-9193
REYNES J -P ET AL: "ESCHERICHIA COLI THYMIDYLATE KINASE: MOLECULAR CLONING, NUCLEOTIDE SEQUENCE, AND GENETIC ORGANIZATION OF THE CORRESPONDING TMK LOCUS" JOURNAL OF BACTERIOLOGY,WASHINGTON, DC,US, vol. 178, no. 10, May 1996 (1996-05), pages 2804-2812, XP000952533 ISSN: 0021-9193
WEHMEIER U F ET AL: "CLONING OF THE ESCHERICHIA COLI SOR GENES FOR L-SORBOSE TRANSPORT AND METABOLISM AND PHYSICAL MAPPING OF THE GENES NEAR METH AND ICLR" JOURNAL OF BACTERIOLOGY,WASHINGTON, DC,US, vol. 174, no. 23, December 1992 (1992-12), pages 7784-7790, XP000952310 ISSN: 0021-9193
See also references of EP 1165832A2
ARIGONI F ET AL: "A genome-based approach for the identification of essential bacterial genes" NATURE BIOTECHNOLOGY,US,NATURE PUBLISHING, vol. 16, no. 16, September 1998 (1998-09), pages 851-856-856, XP002124132 ISSN: 1087-0156
BALTZ ET AL: "DNA sequence sampling of the Streptococcus pneumoniae genome to identify novel targets for antibiotic development" MICROBIAL DRUG RESISTANCE,US,LIEBERT, vol. 4, no. 1, 21 March 1998 (1998-03-21), pages 1-9-9, XP002112153 ISSN: 1076-6294
TRIAS AND GORDON: "INNOVATIVE APPROACHES TO NOVEL ANTIBACTERIAL DRUG DISCOVERY" CURRENT OPINION IN BIOTECHNOLOGY,GB,LONDON, vol. 8, no. 8, 1997, pages 757-762-762, XP002119418 ISSN: 0958-1669
TATUSOV R L ET AL: "METABOLISM AND EVOLUTION OF HAEMOPHILUS INFLUENZAE DEDUCED FROM A WHOLE-GENOME COMPARISON WITH ESCHERICHIA COLI" CURRENT BIOLOGY,GB,CURRENT SCIENCE,, vol. 6, no. 3, 1 March 1996 (1996-03-01), pages 279-291-291, XP000857871 ISSN: 0960-9822
FLEISCHMANN R D ET AL: "WHOLE-GENOME RANDOM SEQUENCING AND ASSEMBLY OF HAEMOPHILUS INFLUENZAE RD" SCIENCE,US,AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, vol. 269, no. 5223, 28 July 1995 (1995-07-28), pages 496-498,507-51, XP000517090 ISSN: 0036-8075
ROHDICH, F. ET AL.: "Cytidine 5'-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol" PNAS, vol. 96, no. 21, 12 October 1999 (1999-10-12), pages 11758-11763, XP002132607
POST D A ET AL: "CHARACTERIZATION OF THE HEMA-PRS REGION OF THE ESCHERICHIA COLI ANDSALMONELLA TYPHIMURIUM CHROMOSOMES: IDENTIFICATION OF TWO OPEN READING FRAMES AND IMPLICATIONS FOR PRS EXPRESSION" JOURNAL OF GENERAL MICROBIOLOGY,GB,SOCIETY FOR MICROBIOLOGY, READING, vol. 139, no. 2, 1993, pages 259-266, XP000923112 ISSN: 0022-1287
GREEN J M ET AL: "CHARACTERIZATION AND SEQUENCE OF ESCHICHIA COLI PABC, THE GENE ENCODING AMINODEOXYCHORISMATE LYASE, A PYRIDOXAL PHOSPHATE-CONTAINING ENZYME" JOURNAL OF BACTERIOLOGY,WASHINGTON, DC,US, vol. 174, no. 16, August 1992 (1992-08), pages 5317-5323, XP000952311 ISSN: 0021-9193
REYNES J -P ET AL: "ESCHERICHIA COLI THYMIDYLATE KINASE: MOLECULAR CLONING, NUCLEOTIDE SEQUENCE, AND GENETIC ORGANIZATION OF THE CORRESPONDING TMK LOCUS" JOURNAL OF BACTERIOLOGY,WASHINGTON, DC,US, vol. 178, no. 10, May 1996 (1996-05), pages 2804-2812, XP000952533 ISSN: 0021-9193
WEHMEIER U F ET AL: "CLONING OF THE ESCHERICHIA COLI SOR GENES FOR L-SORBOSE TRANSPORT AND METABOLISM AND PHYSICAL MAPPING OF THE GENES NEAR METH AND ICLR" JOURNAL OF BACTERIOLOGY,WASHINGTON, DC,US, vol. 174, no. 23, December 1992 (1992-12), pages 7784-7790, XP000952310 ISSN: 0021-9193
See also references of EP 1165832A2
Attorney, Agent or Firm:
VOSSIUS & PARTNER (Siebertstrasse 4 München, DE)
Download PDF:
Claims:
CLAIMS
| 1. | A method for identifying an antagonist or inhibitor of the expression of a gene encoding a polypeptide essential for bacterial growth or survival wherein said gene is selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or a fragment, derivative or ortholog thereof, said method comprising the steps of (a) testing a candidate antagonist or inhibitor or a sample comprising a plurality of said candidate antagonists or inhibitors for the inhibition or reduction of transcription of said gene or a fragment or derivative thereof; or (b) testing a candidate antagonist or inhibitor or a sample comprising a plurality of said candidate antagonists or inhibitors for the inhibition or reduction of translation of mRNA transcribed from said gene or a fragment or derivative thereof; and (c) identifying an antagonist or inhibitor or a sample comprising a plurality of said candidate antagonists or inhibitors that tests positive in step (a) and/or (b). |
| 2. | A method for testing a candidate antagonist or inhibitor of a polypeptide or a mRNA essential for bacterial growth or survival encoded by a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or a fragment, derivative or ortholog thereof comprising the steps of (a) contacting a bacterial cell with a candidate antagonist or inhibitor or a sample comprising a plurality of said candidate antagonists or inhibitors; and (b) testing whether said contacting leads to cell growth inhibition and/or cell death. |
| 3. | A method for testing a candidate antagonist or inhibitor of the function of a gene essential for bacterial growth or survival wherein said gene is selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or a fragment, derivative or ortholog thereof, comprising the steps of (a) contacting a bacterial cell comprising said gene with a candidate antagonist or inhibitor or a sample comprising a plurality of said candidate antagonists or inhibitors; and (b) testing whether said contacting leads to cell growth inhibition and/or cell death. |
| 4. | The method of any one of claims 1 to 3 further comprising identifying an antagonist or inhibitor, optionally from said sample of candidate antagonists or inhibitors. |
| 5. | The method of any one of claims 1 to 4 wherein said inhibitor or antagonist is further improved by peptidomimetics or by applying phage display or combinatorial library technique step (s). |
| 6. | A method for designing an improved antagonist or inhibitor for the treatment of a bacterial infection or disorder or disease related to a bacterial infection comprising the steps (a) identification of the binding site of an antagonist or inhibitor to the polypeptide ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or obtained by or identified by the method of any one of claims 1 to 5 by sitedirected mutagenesis and chimeric polypeptide studies; (b) molecular modeling of both the binding site of said antagonist or inhibitor and the structure of said polypeptide; and (c) modification of said antagonist or inhibitor to improve its binding specificity or affinity for the polypeptide. |
| 7. | An antagonist or inhibitor of the activity of a polypeptide encoded by a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b 1808, yeaA, yag F, b 1983, yid D, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or fragment, derivative or ortholog thereof or of the expression of a gene encoding said polypeptide or said fragment, derivative or ortholog or obtained by or identified by the method of any one of claims 1 to 6. |
| 8. | A method for producing a therapeutic agent comprising synthesizing the antagonist or inhibitor identified, tested or designed according to the method of any one of claims 1 to 6 or the antagonist or inhibitor of claim 7 or an analog or derivative thereof. |
| 9. | A method for producing a composition comprising the steps of the method of any one of claims 1 to 6 or synthesizing the antagonist or inhibitor of claim 7 and formulating said inhibitor or antagonist in a pharmaceutically acceptable form. |
| 10. | A composition comprising an antagonist or inhibitor of claim 7, the therapeutic agent produced by the method of claim 8 or the antagonist or inhibitor obtained by or identified in the method of any one of claims 1 to 6 or produced according to claim 9 and optionally a pharmaceutically acceptable carrier. |
| 11. | The composition of claim 10 which is a pharmaceutical composition. |
| 12. | The composition of claim 10 which is a kit. |
| 13. | The composition of any one of claims 10 to 12 further comprising an antibiotic and/or cytokine. |
| 14. | Use of a polypeptide encoded by a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig.1 or a fragment, derivative or ortholog thereof or of any of said genes for the identification of an antagonist or inhibitor of the activity of said polypeptide or said fragment, derivative or ortholog or of the expression of a gene encoding said polypeptide or said fragment, derivative or ortholog. |
| 15. | Use of an antagonist or inhibitor of claim 7, the therapeutic agent produced by the method of claim 8 or the antagonist or inhibitor obtained by or identified in the method of any one of claims 1 to 6 or produced according to claim 9 or identified by the use of any of the claims for the preparation of a pharmaceutical composition for the treatment of (a) bacterial infection (s), disorder (s) and/or disease (s) related to bacterial infections. |
| 16. | A method for treating or preventing bacterial infections or diseases or disorders related to bacterial infections comprising the step of administering to a subject in need thereof the antagonist or inhibitor obtained by or identified in the method of any one of claims 1 to 6 or produced according to claim 9 optionally comprised in the pharmaceutical composition according to claim 11. |
| 17. | Use of a polypeptide encoded by a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig.1 or a fragment, derivative or ortholog thereof or any of said genes for screening for polypeptides interacting with said polypeptide using protein protein interaction technologies, and/or for validating such interaction as being essential for bacterial survival and/or for screening for antagonists or inhibitors of such interaction. |
| 18. | Use of a polypeptide encoded by a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or a fragment, derivative or ortholog thereof or any of said genes for screening of polypeptide for polypeptide binding to said polypeptide, and/or for validating the peptides binding to said polypeptide as preventing growth of bacteria or being lethal to bacteria upon expression of said polypeptides in said bacteria, and/or for screening for small molecules competitively displacing said peptides. |
| 19. | Use of conditional mutants in a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1, or a fragment, derivative or ortholog thereof or of surrogate ligands against said gene expressed in bacteria to induce a lethal phenotype in bacteria and/or for the analysis of said bacteria for surrogate markers by comparison of RNA or protein profiles in said bacteria with RNA or protein profiles in wild type bacteria, and/or the use of said surrogate markers for the identification of antagonists of the essential function of said gene. |
| 20. | A method for identifying or isolating a surrogate marker comprising the steps as described in claim 19. |
| 21. | A method for identifying or isolating a surrogate marker comprising the steps of (a) inducing a lethal phenotype in bacteria containing a conditional mutant of a gene selected from the group consisting of ygbB, yfhC, yacE, ychB, yejD, yrfl, yggJ, yjeE, yiaO, yrdC, yhbC, ygbP, ybeY, gcpE, kdtB, pfs, ycaJ, b1808, yeaA, yagF, b1983, yidD, yceG and/or yjbC, the sequence of said genes being shown in Fig. 1; and (b) analysing said bacteria comparing the RNA or protein profile of said bacteria with wild type bacteria. |
Description:
INTERNATIONALSEARCHREPORT Inte.onalApplicationNo PCT/EP00/03135 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category° Citationofdocument,withindication,whereappropriate,oftherele
vantpassagesRelevanttodaimNo. AARIGONIFETAL:"Agenome-basedapproach1-6,14, fortheidentificationofessential17-21 bacterialgenes" NATUREBIOTECHNOLOGY,US,NATUREPUBLISHING, vol.16,no.16,September1998(1998-09), pages851-856-856,XP002124132 ISSN:1087-0156 abstract page855,column1,paragraph4-column2, paragraph1 page856,column2,line57-line58 ABALTZETAL:"DNAsequencesamplingof1-6,14, theStreptococcuspneumoniaegenometo17-21 identifynoveltargetsforantibiotic development" MICROBIALDRUGRESISTANCE,US,LIEBERT, vol.4,no.1,21March1998(1998-03-21), pages1-9-9,XP002112153 ISSN:1076-6294 abstract;tables1,4 page8,column1,paragraph2 ATRIASANDGORDON:"INNOVATIVE APPROACHES1-6,14, TONOVELANTIBACTERIALDRUGDISCOVERY"17-21 CURRENTOPINIONIN BIOTECHNOLOGY,GB,LONDON, vol.8,no.8,1997,pages757-762-762, XP002119418 ISSN:0958-1669 thewholedocument ATATUSOVRLETAL:"METABOLISMAND1-6,14, EVOLUTIONOFHAEMOPHILUSINFLUENZAE17-21 DEDUCEDFROMAWHOLE-GENOMECOMPARISON WITHESCHERICHIACOLI" CURRENTBIOLOGY,GB,CURRENTSCIENCE" vol.6,no.3,1March1996(1996-03-01), pages279-291-291,XP000857871 ISSN:0960-9822 thewholedocument AFLEISCHMANNRDETAL:"WHOLE-GENOME 1-6,14, RANDOMSEQUENCINGANDASSEMBLYOF17-21 HAEMOPHILUSINFLUENZAERD" SCIENCE,US,AMERICANASSOCIATIONFORTHE ADVANCEMENTOFSCIENCE" vol.269,no.5223, 28July1995(1995-07-28),pages 496-498,507-51,XP000517090 ISSN:0036-8075 thewholedocument 2 2 INTERNATIONALSEARCHREPORT Inte ; onal ApplicationNo PCT/EP00/03135 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT CategoryCitationofdocument,withindication,whereappropriate,o
ftherelevantpassagesRelevanttoclaimNo. P,AWO9947553A(ARIGONIFABRIZIO;PEITSCH1-6,14, MANUELC(CH);LOFERERHANNES(DE);GLAX)17-21 23September1999(1999-09-23) thewholedocument P,AROHDICH,F.ET AL.:"Cytidine1-6,14, 5'-triphosphate-dependentbiosynthesisof17-21 isoprenoids:YgbPproteinofEscherichia colicatalyzestheformationof 4-diphosphocytidyl-2-C-methylerythritol" PNAS, vol.96,no.21, 12October1999(1999-10-12),pages 11758-11763,XP002132607 abstract AWO9509925A(ZENECALTD;HAWKESTIMOTHY1-6,14, ROBERT(GB))13April1995(1995-04-13)17-21 abstract;claims1,8 AWO9635804A(MERCK&COINC POMPLIANO1-6,14, DAVIDL(US);BRAMHILLDAVID(US);CUNNI)17-21 14November1996(1996-11-14) abstract;claims1,5 AWO9835054A(RIBOGENEINC)1-6,14, 13August1998(1998-08-13)17-21 abstract;claims1,4,8,29 AWO9914311A(SMITHKLINEBEECHAMCORP1-6,14, ;COLEMANKENNETH(US);CRITCHLEYIANA17-21 (US)25March1999(1999-03-25) abstract;claims1,3 APOSTDAETAL:"CHARACTERIZATIONOFTHE1-6,14, HEMA-PRSREGIONOFTHEESCHERICHIACOLI17-21 ANDSALMONELLATYPHIMURIUMCHROMOSOMES: IDENTIFICATIONOFTWOOPENREADINGFRAMES ANDIMPLICATIONSFORPRSEXPRESSION" JOURNALOFGENERALMICROBIOLOGY,GB,SOCIETY FORMICROBIOLOGY,READING, vol.139,no.2,1993,pages259-266, XP000923112 ISSN:0022-1287 abstract page265,column1,paragraph4 2 2 INTERNATIONALSEARCHREPORT Intel znal ApplicationNo PCT/EP00/03135 C.(Continuation)DOCUMENTSCONSIDERED TOBERELEVANT Category°Citationofdocument,withindication,whereappropnate,
oftherelevantpassagesRelevanttoclaimNo. AGREENJMETAL:"CHARACTERIZATIONAND1-6,14, SEQUENCEOFESCHICHIACOLIPABC,THEGENE17-21 ENCODINGAMINODEOXYCHORISMATELYASE,A PYRIDOXALPHOSPHATE-CONTAININGENZYME" JOURNALOFBACTERIOLOGY,WASHINGTON,DC,US, vol.174,no.16,August1992(1992-08), pages5317-5323,XP000952311 ISSN:0021-9193 abstract AREYNESJ-PETAL:"ESCHERICHIACOLI1-6,14, THYMIDYLATEKINASE:MOLECULARCLONING,17-21 NUCLEOTIDESEQUENCE,ANDGENETIC ORGANIZATIONOFTHECORRESPONDINGTMK LOCUS" JOURNALOFBACTERIOLOGY,WASHINGTON,DC,US, vol.178,no.10,May1996(1996-05), pages2804-2812,XP000952533 ISSN:0021-9193 abstract AWEHMEIERUFETAL:"CLONINGOFTHE1-6,14, ESCHERICHIACOLISORGENESFORL-SORBOSE17-21 TRANSPORTANDMETABOLISMANDPHYSICAL MAPPINGOFTHEGENESNEARMETHANDICLR" JOURNALOFBACTERIOLOGY,WASHINGTON,DC,US, vol.174,no.23,December1992(1992-12), pages7784-7790,XP000952310 ISSN:0021-9193 abstract 2 ,., rnationai appiication Nio. PCT/EP00/03135 Box)Observationswherecertainclaimswerefoundunsearchable(Cont
inuationofitem1offirstsheet) ThisInternationalSearchReporthasnotbeenestablishedinrespecto
fcertainclaimsunderArticle17(2)(a)forthefollowingreasons. 1.ijClaimsNos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi
sAuthority,namely: seeFURTHERINFORMATIONsheetPCT/ISA/210 2.EClaimsNos.:7-13,15,16 becausetheyrelatetopartsoftheInternationalApplicationthatdon
otcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulInternationalSearchcanbecarriedout,s
pecifically: seeFURTHERINFORMATIONsheetPCT/ISA/210 3.faimsNos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit
hthesecondandthirdsentencesofRule6.4(a). Box11Observationswhereunityofinventionislacking(Continuation
ofitem2offirstsheet) ThisInternationalSearchingAuthorityfoundmultipleinventionsin
thisinternationalapplication,asfollows: seeadditionalsheet 1.As allrequiredadditionalsearchfeesweretimelypaidbytheapplicant,
thisInternationalSearchReportcoversall searchableclaims. 2.as hallsearchableclaimscouldbesearchedwithouteffortjustifyingan
additionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.Asonlysomeoftherequiredadditionalsearchfeesweretimelypaidb
ytheapplicant,thisInternationalSearchReport coversonlythoseclaimsforwhichfeeswerepaid,specificallyclaims
Nos.: 1-21(partially) 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant
.Consequently,thisInternationalSearchReportis restrictedtotheinventionfirstmentionedintheclaims;itiscovere
dbyclaimsNos.: RemarkonProtestTheadditionalsearchfeeswereaccompaniedbytheap
plicant'sprotest. !Noprotestaccompaniedthepaymentofadditionalsearchfees. au FURTHER INFORMATION CONTINUED FROM PCT/) SA/ 210 Continuation of Box I. 1 Although claim 16 is directed to a method of treatment of the human/animal body, the search has been carried out and based on the alleged effects of the compounds/compositions (but see reasoning for the limitation of the search according to article 5 and 6 PCT).
Continuation of Box I. 1 Rule 39.1 (iv) PCT-Method for treatment of the human or animal body by therapy Continuation of Box 1.2 Claims Nos.: 7-13,15,16 Present claims 7-13,15,16 relate to products defined by reference to a desirable characteristic or property, namely being"identified by the method of any one of claims 1 to 6". ~ The claims cover all products having this characteristic or property, whereas the application provides no support within the meaning of Article 6 PCT and/or disclosure within the meaning of Article 5 PCT for such products. In the present case, the claims so lack support, and the application so lacks disclosure, that a meaningful search over the claimed scope is impossible. Independent of the above reasoning, the claims also lack clarity (Article 6 PCT). An attempt is made to define the products by reference to a result to be achieved. Again, this lack of clarity in the present case is such as to render a meaningful search over the claimed scope impossible. Consequently, the search has not been carried out for these claims.
The applicant's attention is drawn to the fact that claims, or parts of claims, relating to inventions in respect of which no international search report has been established need not be the subject of an international preliminary examination (Rule 66.1 (e) PCT). The applicant is advised that the EPO policy when acting as an International Preliminary Examining Authority is normally not to carry out a preliminary examination on matter which has not been searched. This is the case irrespective of whether or not the claims are amended following receipt of the search report or during any Chapter II procedure.
FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 1-21 (partially) Method for identifying antimicrobial agents using ygbB or ygbP 2. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yfhC 3. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yacE 4. Claims: 1-21 (partially) Method for identifying antimicrobial agents using ychB 5. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yejD 6. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yrfI 7. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yggJ 8. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yjeE 9. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yiaO 10. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yrdC 11. Claims: 1-21 (partially) FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 Method for identifying antimicrobial agents using yhbC 12. Claims: 1-21 (partially) Method for identifying antimicrobial agents using ybeY 13. Claims: 1-21 (partially) Method for identifying antimicrobial agents using gcpE 14. Claims: 1-21 (partially) Method for identifying antimicrobial agents using kdtB 15. Claims: 1-21 (partially) Method for identifying antimicrobial agents using pfs 16. Claims: 1-21 (partially) Method for identifying antimicrobial agents using ycaJ 17. Claims: 1-21 (partially) Method for identifying antimicrobial agents using bl808 18. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yeaA 19. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yagF 20. Claims: 1-21 (partially) Method for identifying antimicrobial agents using bl983 21. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yidD 22. Claims: 1-21 (partially) FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 Method for identifying antimicrobial agents using yceG 23. Claims: 1-21 (partially) Method for identifying antimicrobial agents using yjbC INTERNATIONALSEARCHREPORT Intei onal ApplicationNo mformation on patent tamiiy members PCT/EP 00/03135 PatentdocumentPublicationPatentfamily Publication citedinsearchreportdatemember(s)date WO9842875A01-10-1998US5858367A12-01-1999 AU6589098A20-10-1998 EP0975801A02-02-2000 WO9947553A23-09-1999AU2947399A11-10-1999 WO9509925A13-04-1995AU686231B05-02-1998 AU7702394A01-05-1995 EP0722505A24-07-1996 HU73691A30-09-1996 JP9503131T31-03-1997 NZ273643A19-12-1997 WO9635804A14-11-1996NONE WO9835054A13-08-1998AU6155398A26-08-1998 US5998159A07-12-1999 WO9914311A25-03-1999EP1023434A02-08-2000