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Title:
REMOVAL OF PRIONS FROM BLOOD, PLASMA AND OTHER LIQUIDS
Document Type and Number:
WIPO Patent Application WO/2000/043782
Kind Code:
A2
Abstract:
Devices such as flow through columns, substrates such as spherical polymer beads, and methods of using such to remove prions from any liquid sample are disclosed. A surface of a substrate is coated with a prion complexing agent, such as a metal salt (e.g. sodium) of phosphotungstic acid. Blood or plasma passing through a column containing beads coated with prion complexing agent are rendered prion free. The beads may be comprised of a ferromagnetic core to facilitate removal of the beads from the sample.

Inventors:
PRUSINER STANLEY B (US)
SAFAR JIRI G (US)
Application Number:
PCT/US1999/030167
Publication Date:
July 27, 2000
Filing Date:
December 17, 1999
Export Citation:
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Assignee:
UNIV CALIFORNIA (US)
PRUSINER STANLEY B (US)
SAFAR JIRI G (US)
International Classes:
A01N1/02; G01N33/53; A61K35/14; A61L2/00; A61L2/16; A61M1/34; B01D15/00; B01D43/00; B03C1/00; B03C1/02; C07K14/47; C07K16/28; C12N11/00; G01N33/531; G01N33/566; G01N33/569; G01N33/68; G01N; (IPC1-7): G01N33/53
Domestic Patent References:
WO1999042487A11999-08-26
WO1993023432A11993-11-25
WO1997040861A11997-11-06
WO1997043649A11997-11-20
Foreign References:
US4300905A1981-11-17
US4320086A1982-03-16
US5521060A1996-05-28
US5858326A1999-01-12
Other References:
GABIZON R. ET AL.: "Immunoaffinity purification and neutralization of scrapie prion infectivity" PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 6617-6621, XP002136042
PAN K.-M. ET AL.: "PURIFICATION AND PROPERTIES OF THE CELLULAR PRION PROTEIN FROM SYRIAN HAMSTER BRAIN" PROTEIN SCIENCE,GB,CAMBRIDGE UNIVERSITY PRESS, CAMBRIDGE, vol. 1, 1 January 1992 (1992-01-01), pages 1343-1352, XP002043228 ISSN: 0961-8368
SAFAR J. ET AL.: "Eight prion strains have PrPSc molecules with different conformations" NATURE MEDICINE, vol. 4, no. 10, 1998, pages 1157-1165, XP002136041
SAIDKHANOV S.S. ET AL.: "Changes in catalytic properties of 12-heteropolyacids in reaction of dihydrogen evolution from water induced by their immobilization on anion-exchange polymers" JOURNAL OF MOLECULAR CATALYSIS, vol. 21, 1983, pages 365-373, XP000905500
CHEMICAL ABSTRACTS, vol. 121, no. 16, 17 October 1994 (1994-10-17) Columbus, Ohio, US; abstract no. 189817, ALPATOVA N.M. ET AL.: "Comparison of electrochemical behavior of heteropolyacids in solution and immobilized in a conducting polymer film" XP002137872 & ELEKTROKHIMIYA, vol. 30, no. 7, 1994, pages 859-866, XP000908954
KAMADA M. ET AL.: "Dispersion and fixation of 12-tungstophosphate anion on a silica surface modified with silane agents having an amine group and their catalytic properties" BULL. CHEM. SOC. JPN., vol. 66, 1993, pages 3565-3570, XP000906871
KIMBERLIN R.H. ET AL.: "Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions" ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 30, no. 3, 1986, pages 409-413, XP000905284
Attorney, Agent or Firm:
Bozicevic, Karl (Field & Francis LLP Suite 200 200 Middlefield Road Menlo Park, CA, US)
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Claims:
That which is claimed is:
1. A method of removing prions from a sample, comprising the steps of : contacting a sample in a flowable liquid state with a solid substrate comprised of a prion complexing agent; and allowing the sample to remain in contact with the substrate for time such that prions in the sample bind to the substrate.
2. The method of claim 1, wherein the complexing agent is selected from the group consisting of a heteropoly acid or salt thereof, a metal salt of phosphotungstic acid, a peptide and an antibody.
3. The method of claim 1, wherein the complexing agent is an antibody and the antibody selectively binds to PrPSc.
4. The method of claim 1, wherein the sample comprises a human body fluid.
5. The method of claim 4, wherein the human body fluid comprises human blood.
6. The method of claim 4, wherein the substrate is in the form of spherical beads comprised of a ferromagnetic metal having a polymer coated thereon and wherein the complexing agent is a metal salt of phosphotungstic acid.
7. The method of claim 6, further comprising: removing the substrate from contact with the human body fluid by application of magnetic energy.
8. A device for removing prions from a sample, comprising: a water insoluble polymer; and a prion complexing agent coated on a surface of the polymer.
9. The device of claim 8, further comprising: a ferromagnetic metal wherein the polymer is coated on the ferromagnetic metal and the complexing agent is selected from the group consisting of phosphotungstic acid or salts thereof and an antibody which binds PrPSc.
10. A prion free liquid, characterized by being subjected to the method of claim 1.
11. The prion free liquid of claim 10, wherein the liquid is further characterized by being derived from a human.
12. The prion free liquid of claim 11, wherein the liquid is human blood.
13. The prion free liquid of claim 11, wherein the liquid is human plasma.
14. A flow through device for removing prions from a liquid sample, comprising: a housing through which a liquid sample flows; and substrate surfaces comprised of prion complexing agent.
15. The device of claim 14, wherein the housing is cylindrical and the substrate is polymer beads having sodium phosphotungstate coated on their surface.
Description:
INTERNATIONALSEARCHREPORT Inte. ional ApplicationNo PCT/US99/30167 C.(Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT CategoryCitation ofdocument,withindication,whereappropriate,oftherelevantpass agesRelevanttoclaimNo. XWO9740861A(IMMUNOAG;BARRETTNOEL1-5,8, (AT);EIBLJOHANN(AT);DORNERFRIEDRICH10-14 ()6November1997(1997-11-06) abstract claims XPAN K.-M. ET AL. :"PURIFICATIONAND1,2,4,5, PROPERTIESOFTHECELLULARPRIONPROTEIN8,10-14 FROMSYRIANHAMSTERBRAIN" PROTEINSCIENCE,GB,CAMBRIDGEUNIVERSITY PRESS,CAMBRIDGE, vol.1,1January1992(1992-01-01),pages 1343-1352,XP002043228 ISSN:0961-8368 Ypage1350,column1,paragraph4-page6,7,9,15 1350,column2,paragraph2 XWO9743649A(WINNACKERERNSTLUDWIG1,2,4,5, ;WEISSSTEFAN(DE);EDENHOFERFRANK(DE);8,10-14 R)20November1997(1997-11-20) Ypage2,line25-286,7,9,15 page7,line23-30 claims2,13-15 YSAFARJ.ETAL.: "Eightprionstrains6,7,9,15 havePrPScmoleculeswithdifferent conformations" NATUREMEDICINE, vol.4,no.10,1998,pages1157-1165, XP002136041 page1161,column1,line32-35 XUS4300905A(BLEISTEINERMANFREDETAL)8,9,14, 17November1981(1981-11-17)15 abstract example1 XUS4320086A(REISSANDRE)8,9,14, 16March1982(1982-03-16)15 column2,line4-11 XUS5521060A(HOENESJOACHIMETAL)8,9,14, 28May1996(1996-05-28)15 abstract example1 XSAIDKHANOVS.S.ETAL.:"Changesin8,9,14, catalyticpropertiesof12-heteropolyacids15 inreactionofdihydrogenevolutionfrom waterinducedbytheirimmobilizationon anion-exchangepolymers" JOURNALOFMOLECULARCATALYSIS, vol.21,1983,pages365-373,XP000905500 page366 -/- 2 INTERNATIONALSEARCHREPORT lnteonalApplicationNo PCT/US99/30167 C.(Continuation)DOCUMENTSCONSIDERED TO BE RELEVANT Category° Citation ofdocument,withindication,whereappropriate,of therelevantpassagesRelevanttoclaimNo. XCHEMICALABSTRACTS,vol.121,no.16,8,9,14, 17October1994(1994-10-17)15 Columbus,Ohio,US; abstractno.189817, ALPATOVAN.M.ETAL.:"Comparisonof electrochemicalbehaviorof heteropolyacidsinsolutionand immobilizedinaconductingpolymerfilm" XP002137872 abstract &ELEKTROKHIMIYA, vol.30,no.7,1994,pages859-866, XP000908954 thewholedocument XKAMADA M. ET AL.:"Dispersionand8,9,14, fixationof12-tungstophosphateanionona15 silicasurfacemodifiedwithsilaneagents havinganaminegroupandtheircatalytic properties" BULL.CHEM.SOC.JPN., vol.66,1993,pages3565-3570, XP000906871 thewholedocument AUS5858326A(KISILEVSKYROBERTETAL)8,9,14, 12January1999(1999-01-12)15 column9,line26-28 AKIMBERLINR.H.ETAL.:"Suppressionof scrapieinfectioninmiceby heteropolyanion23,dextransulfate,and someotherpolyanions" ANTIMICROBIALAGENTSANDCHEMOTHERAPY, vol.30,no.3,1986,pages409-413, XP000905284 abstract 2 ".. ernationalapplicationNo. INTERNATIONALSEARCHREPORTPCT/US99/30167 Box IObservationswherecertainclaimswerefoundunsearchable(Continu ationofitem1offirstsheet) ThisInternationalSearchReporthasnotbeenestablishedinrespecto fcertainclaimsunderArticle17(2)(a)forthefollowingreasons: 1.F-IClaimsNos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi sAuthority,namely: 2.njClaimsNos.: becausetheyrelatetopartsoftheInternationalApplicationthatdon otcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulInternationalSearchcanbecarriedout,s pecifically: 3.ClaimsNos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4(a). Box11Observationswhereunityofinventionislacking(Continuation ofitem2offirstsheet) ThisInternationalSearchingAuthorityfoundmultipleinventionsin thisinternationalapplication,asfollows: seeadditionalsheet 1.gAsallrequiredadditionalsearchfeesweretimelypaidbytheappli cant,thisInternationalSearchReportcoversall searchableclaims. 2.as aitsearchableclaimscouldbesearchedwithouteffortjustifyingana dditionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.Asonlysomeoftherequiredadditionalsearchfeesweretimelypaidb ytheapplicant,thisInternationalSearchReport coversonlythoseclaimsforwhichfeeswerepaid,specificallyclaims Nos.: 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant .Consequently,thisInternationalSearchReportis restrictedtotheinventionfirstmentionedintheclaims;itiscovere dbyclaimsNos.: RemarkonProtestTheadditionalsearchfeeswereaccompaniedbytheap plicant'sprotest. jNoprotestaccompaniedthepaymentofadditionalsearchfees. I A I nternational Application No. PCTAJS 99 80167 FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 1-2 (in part), 4-5 (in part), 6-7,8-9 (in part), 10-14 (in part), 15 A method of removing prions from a sample, comprising the steps of: contacting the sample with a solid substrate comprised of a prion complexing agent selected from the group consisting of heteropoly acid or a salt thereof, and a metal salt of phosphotungstic acid; and allowing the sample to remain in contact with the substrate for time such that prions in the sample bind to the substrate.

2. Claims: 1-2 (in part), 3,4-5 (in part), 8-9 (in part), 10-14 (in part) A method of removing prions from a sample, comprising the steps of: contacting the sample with a solid substrate comprised of a prion complexing agent selected from the group consisting of a peptide and an antibody; and allowing the sample to remain in contact with the substrate for time such that prions in the sample bind to the substrate. INTERNATIONALSEARCHREPORT Intc ionalApplicationNo Information on patent family members PCT/US 99/30167 Patent document Publication Patent family Publication citedinsearchreportdate member(s)date WO9942487A26-08-1999US 5977324 A 02-11-1999 AU 2585499 A 06-09-1999 WO9323432A25-11-1993AU 4376093 A 13-12-1993 WO9740861A06-11-1997AT 403477 B 25-02-1998 AT 78096 A 15-07-1997 AU 2561297 A 19-11-1997 EP 0900089 A 10-03-1999 NO 984979 A 23-12-1998 WO9743649A20-11-1997EP 0914614 A 12-05-1999 US4300905A17-11-1981DE 2926068 A 08-01-1981 AT 3169 T 15-05-1983 CS 221928 B 29-04-1983 DD 151820 A 04-11-1981 DE 3062883 D 01-06-1983 EP 0021245 A 07-01-1981 JP 1473199 C 27-12-1988 JP 56008550 A 28-01-1981 JP 63021865 B 09-05-1988 SU 1015834 A 30-04-1983 YU 167480 A 30-04-1984YU 167480 A 30-04-1984 US4320086A16-03-1982NONE US5521060A28-05-1996DE 3940010 A 06-06-1991 US 5382523 A 17-01-1995 AT 118552 T 15-03-1995 AU 628688 B 17-09-1992 AU 6694990 A 06-06-1991 CA 2031238A,C 03-06-1991 CN 1052376A,B 19-06-1991 CS 9005936 A 18-03-1992 DE 59008475 D 23-03-1995 DK 431456 T 17-07-1995 EP 0431456 A 12-06-1991 ES 2069661 T 16-05-1995 FI 905925A,B,03-06-1991 GR 3015363 T 30-06-1995 HU 56631A,B 30-09-1991 IE 65537 B 01-11-1995 IL 96473 A 15-03-1995 JP 1961399 C 10-08-1995 JP 3191799 A 21-08-1991 JP 6087790 B 09-11-1994 KR 9501124 B 11-02-1995 MX 23524 A 01-10-1993 NO 300244 B 28-04-1997 NZ 236249 A 25-02-1993 PL 166907 B 31-07-1995 PT 96029A,B 13-09-1991 SK 280136 B 06-08-1999 RU 2052819 C 20-01-1996 US 5240860 A 31-08-1993 ZA 9009625 A 30-10-1991 INTERNATIONALSEARCHREPORT Inte ionalApplicationNo Informationonpatent familymembers PCT/US 99/30167 PCT/US 99/30167 PatentdocumentPublicationPatentfamilyPublication citedinsearchreportdatemember(s)date US5858326A12-01-1999AU5889696A24-12-1996 CA2219447A12-12-1996 WO9639129A12-12-1996