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Title:
HUMAN HOMOLOGUES OF PROTEINS REGULATED BY CIRCADIAN RHYTHMS
Document Type and Number:
WIPO Patent Application WO/2000/042172
Kind Code:
A2
Abstract:
The invention provides human proteins associated with circadian rhythms (CIRYP) and polynucleotides which identify and encode CIRYP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with expression of CIRYP.

Inventors:
HILLMAN JENNIFER L (US)
TANG Y TOM (US)
LU DYUNG AINA M (US)
AZIMZAI YALDA (US)
Application Number:
PCT/US2000/001086
Publication Date:
July 20, 2000
Filing Date:
January 14, 2000
Export Citation:
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Assignee:
INCYTE PHARMA INC (US)
HILLMAN JENNIFER L (US)
TANG Y TOM (US)
LU DYUNG AINA M (US)
AZIMZAI YALDA (US)
International Classes:
G01N33/50; A61K38/00; A61K39/00; A61K45/00; A61P1/00; A61P1/16; A61P1/18; A61P5/14; A61P13/02; A61P13/08; A61P15/00; A61P15/08; A61P19/00; A61P21/00; A61P25/00; A61P25/08; A61P25/14; A61P25/16; A61P25/18; A61P25/20; A61P25/28; A61P27/06; A61P27/12; A61P27/16; A61P31/18; A61P35/00; A61P37/02; C07K14/47; C07K16/18; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N15/09; C12P21/02; C12Q1/68; G01N33/15; G01N33/53; G01N33/566; (IPC1-7): C12N5/10; A01K67/027; C07K14/47; C07K16/18; C12N15/10; C12N15/63; G01N33/48
Domestic Patent References:
WO1999040189A21999-08-12
WO1999047540A11999-09-23
Other References:
LIEBMANN P.M. ET AL.: "Circadian rhythm of the soluble p75 tumor necrosis factor (sTNF-R75) receptor in humans-a possible explanation for the circadian kinetics of TNF-alpha effects" INTERNATIONAL IMMUNOLOGY, vol. 10, no. 9, September 1998 (1998-09), pages 1393-1396, XP000864584
NCI-CGAP: "National Cancer Institute, Cancer Genome Anatomy Project (CGAP), Tumor Gene Index http://www.ncbi.nlm.nih.gov/ncicgap; ow91d05.x1 Soares_fetal_liver_spleen_1NFLS_S1 Homo sapiens cDNA clone IMAGE:1654185 3'similar to TR:Q94915 Q94915 DREG-2 PROTEIN.;, mRNA sequence." EMBL DATABASE ENTRY AI022747; ACCESSION NO. AI022747,19 June 1998 (1998-06-19), XP002138116
VAN GELDER R.N. ET AL.: "Extent and character of circadian gene expression in Drosophila melanogaster: identification of twenty oscillating mRNAs in the fly head" CURRENT BIOLOGY, vol. 5, no. 12, 1 December 1995 (1995-12-01), pages 1424-1436, XP000864597 cited in the application
C A SMITH ET AL: "A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins" SCIENCE,US,AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, vol. 248, no. 248, 25 May 1990 (1990-05-25), pages 1019-1022, XP002107350 ISSN: 0036-8075
NOPHAR Y ET AL: "SOLUBLE FORMS OF TUMOR NECROSIS FACTOR RECEPTORS (TNF-RS). THE CDNA FOR THE TYPE 1 TNF-R, CLONED USING AMINO ACID SEQUENCE DATA OF ITS SOLUBLE FORM, ENCODES BOTH THE CELL SURFACE AND A SOLUBLE FORM OF THE RECEPTOR" EMBO JOURNAL, vol. 9, no. 10, 1 October 1990 (1990-10-01), pages 3269-3278, XP002025930 ISSN: 0261-4189
See also references of EP 1144598A2
Attorney, Agent or Firm:
Hamlet-cox, Diana (Inc. 3174 Porter Drive Palo Alto, CA, US)
Download PDF:
Claims:
What is claimed is:
1. An isolated polypeptide comprising: a) an amino acid sequence selected from the group consisting of SEQ ID NO: 12, b) a naturally occurring amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 12, c) a biologically active fragment of an amino acid sequence selected from the group consisting of SEQ ID NO: 12, or d) an immunogenic fragment of an amino acid sequence selected from the group consisting of SEQ ID NO: 12.
2. An isolated polypeptide of claim 1, having an amino acid sequence selected from the group consisting of SEQ ID NO: 12.
3. An isolated polynucleotide encoding a polypeptide of claim 1.
4. An isolated polynucleotide of claim 3, having a sequence selected from the group consisting of SEQ ID NO: 34.
5. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 3.
6. A cell transformed with a recombinant polynucleotide of claim 5.
7. A transgenic organism comprising a polynucleotide of claim 5.
8. A method for producing a polypeptide of claim 1, the method comprising: a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide, and said recombinant polynucleotide comprises a promoter sequence operably linked to a polynucleotide encoding the polypeptide of claim 1, and b) recovering the polypeptide so expressed.
9. An isolated antibody which specifically binds to a polypeptide of claim 1.
10. An isolated polynucleotide comprising: a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 34, b) a naturally occurring polynucleotide sequence having at least 70% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO : 34, c) a polynucleotide sequence complementary to a), or d) a polynucleotide sequence complementary to b).
11. An isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide of claim 10.
12. A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 10, the method comprising: a) hybridizing the sample with a probe comprising at least 16 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof.
13. A method of claim 12, wherein the probe comprises at least 30 contiguous nucleotides.
14. A method of claim 12, wherein the probe comprises at least 60 contiguous nucleotides.
15. A pharmaceutical composition comprising an effective amount of a polypeptide of claim I and a pharmaceutically acceptable excipient.
16. A method of treating a disease or condition associated with decreased expression of functional CIRYP, comprising administering to a patient in need of such treatment the pharmaceutical composition of claim 15.
17. A method for screening a compound for effectiveness as an agonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting agonist activity in the sample.
18. A pharmaceutical composition comprising an agonist compound identified by a method of claim 17 and a pharmaceutically acceptable excipient.
19. A method of treating a disease or condition associated with decreased expression of functional CIRYP, comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 18.
20. A method for screening a compound for effectiveness as an antagonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting antagonist activity in the sample.
21. A pharmaceutical composition comprising an antagonist compound identified by a method of claim 20 and a pharmaceutically acceptable excipient.
22. A method for treating a disease or condition associated with overexpression of functional CIRYP, comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 21.
23. A method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence of claim 4, the method comprising: a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.
Description:
INTERNATIONALSEARCHREPORTIntem ial Application No PCT/US00/01086 C. (Continuation) DOCUMENTS CONSIDEREDTOBERELEVANT Category'Citation of document mth indicaLon, where appropnate,oftherelevantpassages RelevanttoclaimNo. P,XWO9947540A(HUMANGENOMESCIENCESINC)1,3,8-16 23September1999(1999-09-23) page135-page136;claims1,7-17 page343 ANCI-CGAP:"National CancerInstitute,1,3 CancerGenomeAnatomyProject(CGAP), TumorGeneIndex http://www.ncbi.nlm.nih.gov/ncicgap; ow91dO5.x1 Soaresfeta1iversp1eenlNFLS SlHomo sapienscDNAcloneIMAGE:16541853'similar toTR:Q94915Q94915DREG-2PROTEIN.;,mRNA sequence." EMBLDATABASEENTRYAI022747;ACCESSION NO.AI022747,19June1998(1998-06-19), XP002138116 AVANGELDERR.N.ETAL.:"Extentand1-17,20, characterofcircadiangeneexpressionin23 Drosophilamelanogaster:identificationof twentyoscillatingmRNAsintheflyhead" CURRENTBIOLOGY, vol.5,no.12, 1December1995(1995-12-01),pages 1424-1436,XP000864597 cited intheapplication thewholedocument ACASMITHETAL:"Areceptorfortumor1-17,20, necrosisfactordefinesanunusualfamily23 ofcellularandviralproteins" SCIENCE,US,AMERICANASSOCIATIONFORTHE ADVANCEMENTOFSCIENCE,, vol.248,no.248, 25May1990(1990-05-25),pages1019-1022, XP002107350 ISSN:0036-8075 ANOPHARYETAL:"SOLUBLEFORMSOFTUMOR1-17,20, NECROSISFACTORRECEPTORS(TNF-RS).THE23 CDNAFORTHETYPE1TNF-R,CLONEDUSING AMINOACIDSEQUENCEDATAOFITSSOLUBLE FORM,ENCODESBOTHTHECELLSURFACEANDA SOLUBLEFORMOFTHERECEPTOR" EMBOJOURNAL, vol.9,no.10, 1October1990(1990-10-01),pages 3269-3278,XP002025930 ISSN:0261-4189 7 int itional appiication No. INTERNATIONAL SEARCHREPORTPCT/US00/01086 BoxIObservationswherecertainclaimswerefound unsearchable (Continuation ofitem1offirstsheet) ThisinternationalSearchReporthasnotbeenestablishedinrespecto fcertainclaimsunderArticle17(2)(a)forthefollowingreasons : 1.j Claims Nos.: becausetheyreiatetosubjectmatternotrequiredtobesearchedbythi sAuthonty,namely : Althoughclaim16isdirectedtoamethodoftreatmentofthehuman/anim al body,thesearchhasbeencarriedoutandbasedontheallegedeffectsof the compound/composition. 2.I'llClaims Nos. : 22 becausetheyreiatetopartsoftheInternational Applicationthatdonotcomplywiththeprescribedrequirementstosuc h anextentthatnomeaningfulInternationalSearchcanbecamedout,spe cificaily : seeFURTHERINFORMATIONsheetPCT/ISA/210 3.7 Claims Nos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4(a). Box 11Observationswhereunityofinventionislacking(Continuationofi tem2offirstsheet) ThisInternationalSearchingAuthorityfoundmultipleinventionsin thisinternationalapplication,asfollows: 1.7 As ail requiredadditionalsearchfeesweretimelypaidbytheapplicant,thi sInternationalSearchReportcoversail 7 searchableclaims. 2.as aitsearchableclaimscouldbesearchedwithouteffortjustifyingana dditionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.ars onsomeoftherequiredadditionalsearchfeesweretimelypaidbytheap plicant,thisInternationalSearchReport covers onlythoseclaimsforwhichfeeswerepaid,specificailyclaimsNos.: 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant .Consequently,thisInternationalSearc.''eu ; restrictedtotheinventionfirstmentionedintheclaims ; st iscoveredbyclaimsNos.: 1-17,20,23partially RemarkonProtest17 The addition31searchfeeswereaccompaniedbytheaDplicant s srotest. J Noprotestaccompamedthepaymentofadditionalsearchfees. . _ FURTHER INFORMATION CONTINUE FROM PCT/tSA/10 1. Claims: 1-17,20,23 (partially) An isolated polypeptide comprising: a) an amino acid sequence of SEQ ID NO: 1, b) a naturally occurring amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1, c) a biologically active fragment of SEQ ID NO: 1, or d) an immunogenic fragment of SEQ ID NO: 1; an isolated polynucleotide encoding said polypeptide; a recombinant polynucleotide comprising a promoter sequence operably linked to said polynucleotide; a cell transformed with said recombinant polynucleotide; a transgenic organism comprising said polynucleotide; a method for producing above mentioned polypeptide; an isolated antibody which specifically binds to said polypeptide; an isolated polynucleotide comprising: a) a polynucleotide sequence of SEQ ID NO: 3, b) a naturally occurring polynucleotide sequence having at least 70% sequence identity to SEQ ID NO: 3, c) a polynucleotide sequence complementary to a), or d) a polynucleotide sequence complemetary to b); an isolated polynucleotide comprising at least 60 contiguous nucleotides of said polynucleotide ; a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of above mentioned polynucleotide; a pharmaceutical composition comprising an effective amount of above mentioned polypetide; a method of treating a disease or condition comprising the administration of said pharmaceutical composition to a patient; methods for screening of a compound comprising inter alia exposing a sample comprising said polypeptide to a compound; a method for screening of a compound for effectiveness in altering expression of a target polynucleotide comprising inter alia exposing a sample comprising said target polynucleotide to a compound.

2. Claims: (partially) Invention II relates to subject-matter as defined above for "invention I", with the exception, that invention II refers to the polypeptide sequence SEQ ID NO: 2 and the respective nucleotide sequence SEQ ID NO: 4.

FURTHER INFORMATION CONTINUED FROM PCTIISA/210 Continuation of Box 1.2 Claims Nos.: 18,19,21,22 Claims 18 and 21 refer to a pharmaceutical composition comprising inter alia an agonist compound or an antagonist compound, respectively, whereby said agonist and antagonist compounds were identified in a certain screening method. Further claims 19 and 22 refer to methods of treating a disease or condition comprising the administration of said pharmaceutical compositions to a patient.

No true technical characterization of such agonist and antagonist compounds is given and no such agonist and antagonist compounds are defined in the application. In consequence, the scope of said claims is ambiguous and vague and their subject-matter is not sufficiently disclosed and supported. No search can be carried out for such purely speculative claims whose wording is a mere recitation of the result to be achieved.

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. INTERNATIONALSEARCHREPORT Interr rlal ApplicationNo Intormation on patent tamily members PCT/US00/01086 Publication Patent family Publication citedin search report date member(s)date WO9940189A12-08-1999AU1049199A 07-06-1999 AU1503099A 05-07-1999 AU2294499A 23-08-1999 EP1029045A 23-08-2000 WO9925825A 27-05-1999 WO9931236A 24-06-1999 WO 9947540A23-09-1999AU3451799A 11-10-1999 AU3072799A 11-10-1999 WO9947538A 23-09-1999