WO2007020081B1 - Composition and method for determination of ck19 expression - Google Patents

Composition and method for determination of ck19 expression

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Publication number
WO2007020081B1
WO2007020081B1 PCT/EP2006/008097 EP2006008097W WO2007020081B1 WO 2007020081 B1 WO2007020081 B1 WO 2007020081B1 EP 2006008097 W EP2006008097 W EP 2006008097W WO 2007020081 B1 WO2007020081 B1 WO 2007020081B1
Authority
WO
WIPO (PCT)
Prior art keywords
primer pair
sample
seq
nucleic acid
primer
Prior art date
Application number
PCT/EP2006/008097
Other languages
French (fr)
Other versions
WO2007020081A1 (en
Inventor
Evriklia Lianidou
Aliki Stathopoulou
Dimitrios Mavroudis
Vasileios Georgoulias
Original Assignee
Medexis S A
Evriklia Lianidou
Aliki Stathopoulou
Dimitrios Mavroudis
Vasileios Georgoulias
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GR20050100430A external-priority patent/GR1005424B/en
Application filed by Medexis S A, Evriklia Lianidou, Aliki Stathopoulou, Dimitrios Mavroudis, Vasileios Georgoulias filed Critical Medexis S A
Priority to JP2008526444A priority Critical patent/JP2009504168A/en
Priority to US11/990,575 priority patent/US20100015604A1/en
Priority to EP06776902.6A priority patent/EP1915461B1/en
Priority to CN200680037658.3A priority patent/CN101365800B/en
Priority to AU2006281569A priority patent/AU2006281569A1/en
Priority to CA002617693A priority patent/CA2617693A1/en
Publication of WO2007020081A1 publication Critical patent/WO2007020081A1/en
Publication of WO2007020081B1 publication Critical patent/WO2007020081B1/en
Priority to US14/031,051 priority patent/US9593374B2/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6804—Nucleic acid analysis using immunogens
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/118—Prognosis of disease development
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/16—Primer sets for multiplex assays

Abstract

Disclosed is a method for quantitative determination of CK-19 mRNA positive cells in a biological sample. The method can be used, for instance, with peripheral blood to detect cancer in a patient. In one embodiment, the method can be used to detect the cancer before initiation of adjuvant treatment, thereby providing information about therapeutic efficacy. Practice of the invention method is sensitive, reliable, and easy to perform.

Claims

72AMENDED CLAIMS received by the International Bureau on 12 February 2007 (12.02.2007)
1 . (cancelled)
2. (cancelled) 5
3. (cancelled)
4. (cancelled)
5. (cancelled)
6. (amended) Primer pair consisting of one primer having the sequence of SEQ ID NO: 1 and one
10 primer having the sequence of SEQ ID NO: 2.
7. (amended) Primer pair according to claim 6, wherein the primers comprises nucleotides, analogues of nucleotides or labels.
8. (amended) Method of quantitative determining 15 the presence in a test sample of a mRNA derived from a gene comprising at least one intron using a pair of primers, wherein at least one of said primers comprises at least one intron-spanning site comprising the steps of
20 (i) forming a reaction mixture comprising nucleic acid amplification reagents, the primer pair of claim 6 and a test sample;
(ii) ■ subjecting the mixture to amplification 25 conditions to generate at least one copy of a nucleic acid sequence complementary to the target sequence; and
(iii) determining the amount of the mRNA in the sample using real-time monitoring 30 during PCR.
9. Method according to claim 8, wherein the 73
test sample is subjected to reverse transcription prior to forming the reaction mixture of step (i) .
10. Method according to claim 8 or 9, wherein the test sample is selected from a blood sample, a sample from the bone marrow and a sample derived from the lymph nodes .
11. Method according to claim 10, wherein the sample is a blood sample.
12. Method according to claim 11, wherein the blood sample is centrifuged before forming the reaction mixture.
13. Method according to any of the claims 8-12, wherein the reaction mixture of step (i) further comprises a housekeeping primer pair.
14. Method according to claim 13, wherein the housekeeping primer pair has the sequence according to SEQ ID 5 and 6.
15. (amended) Diagnostic method of determining the prospects of adjuvant therapy in a patient suffering from cancer comprising the steps of
(i) providing a biological sample from the patient; (ii) isolating nucleic acids from the biological sample; (ϋi) optionally reverse transcribing the isolated nucleic acids, when the origin of the nucleic acid is RNA;
(iv) forming a reaction mixture comprising nucleic acid amplification reagents, the primer pair of claim 6 and an aliquot of the nucleic acids isolated in step (ii) 74
or the reverse transcribed nucleic acid of step (iii) ; (v) subjecting the mixture to amplification conditions to generate at least one copy of a nucleic acid sequence complementary to the target sequence; (vi) quantitating the CK-19 mRNA positive cells in the sample using real-time monitoring during PCR; and (vii) based on the amount of CK-19 mRNA positive cells in the sample determining the prospects of adjuvant therapy.
16. Diagnostic method according to claim 15, wherein the cancer is breast cancer, preferably operable breast cancer.
17. Diagostic method according to claim 15 or 16, wherein the biological sample is a blood sample.
18. Diagnostic method according to any of the claims 15-17, wherein the reaction mixture of step (iii) further comprises a housekeeping primer pair.
19. Method according to claim 18, wherein the housekeeping primer pair has the sequence according to SEQ ID 5 and 6.
20. (amended) Diagnostic kit for amplifying a CK19 target sequence comprising:
(i) the primer pair of claim 6;
(ii) optionally sequences hybridizing to additional markers on cancer cells; (iii) amplification reagents.
21. Diagnostic kit according to claim 20, wherein the amplification reagents comprise the 75
hybridization probes of SEQ ID NO 3 and 4.
22. Diagnostic kit according to claim 20 or 21, wherein the kit further comprises a housekeeping primer pair, preferably with the sequences according to SEQ ID N05 and 6.
23. Diagnostic kit according to any of the claims 20 to 22, wherein the amplification reagents and the primer pair(s) are lyophilized.
24. (amended) A primer pair comprising a first primer having at least about 8 nucleobases of the sequence represented by SEQ ID NO: 1 or SEQ ID NO: 2, the first primer being from between about 10 to about 20 nucleobases in length and further being capable of specifically hybridizing with the CK-19 cDNA sequence shown in Figure 1, and further comprising a second primer having at least about 8 nucleobases of the sequence represented by SEQ ID NO: 1 or SEQ ID NO: 2, the second primer being from between about 10 to about 20 nucleobases in length and further being capable of specifically hybridizing with the CK-19 cDNA sequence shown in Figure 1.
25. (cancelled)
26. The primer pair of claims 24-25, wherein at least one of the first and second primers comprises a modified internucleoside linkage, modified sugar moiety or modified nucleobase.
27. The primer pair of claim 26, wherein at least one of the first and second primers includes at least one locked nucleic acid (LNA) unit.
28. A method of determining the presence in a 76
test sample of a mRNA derived from a gene comprising at least one intron using a pair of primers, wherein at least one of said primers comprises at least one intron-spanning site comprising the steps of (iv) forming a reaction mixture comprising nucleic acid amplification reagents, the primer pair of claims 24-27 and a test sample;
(v) subjecting the mixture to amplification conditions to generate at least one copy of a nucleic acid sequence complementary to the target sequence; and
(vi) determining the amount of the mRNA in the sample using real-time monitoring during PCR.
PCT/EP2006/008097 2005-08-17 2006-08-16 Composition and method for determination of ck19 expression WO2007020081A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP2008526444A JP2009504168A (en) 2005-08-17 2006-08-16 Composition and method for confirming CK19 expression
US11/990,575 US20100015604A1 (en) 2005-08-17 2006-08-16 Composition and method for determination of ck19 expression
EP06776902.6A EP1915461B1 (en) 2005-08-17 2006-08-16 Composition and method for determination of ck19 expression
CN200680037658.3A CN101365800B (en) 2005-08-17 2006-08-16 Composition and method for determination of CK19 expression
AU2006281569A AU2006281569A1 (en) 2005-08-17 2006-08-16 Composition and method for determination of CK19 expression
CA002617693A CA2617693A1 (en) 2005-08-17 2006-08-16 Composition and method for determination of ck19 expression
US14/031,051 US9593374B2 (en) 2005-08-17 2013-09-19 Composition and method for determination of CK19 expression

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GRGR20050100430 2005-08-17
GR20050100430A GR1005424B (en) 2005-08-17 2005-08-17 Method for quantitative determination of ck19 expression
US79514906P 2006-04-25 2006-04-25
US60/795,149 2006-04-25

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US11/990,575 A-371-Of-International US20100015604A1 (en) 2005-08-17 2006-08-16 Composition and method for determination of ck19 expression
US14/031,051 Continuation US9593374B2 (en) 2005-08-17 2013-09-19 Composition and method for determination of CK19 expression

Publications (2)

Publication Number Publication Date
WO2007020081A1 WO2007020081A1 (en) 2007-02-22
WO2007020081B1 true WO2007020081B1 (en) 2007-04-05

Family

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Application Number Title Priority Date Filing Date
PCT/EP2006/008097 WO2007020081A1 (en) 2005-08-17 2006-08-16 Composition and method for determination of ck19 expression

Country Status (7)

Country Link
US (2) US20100015604A1 (en)
EP (1) EP1915461B1 (en)
JP (1) JP2009504168A (en)
KR (1) KR20080036646A (en)
AU (1) AU2006281569A1 (en)
CA (1) CA2617693A1 (en)
WO (1) WO2007020081A1 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8921102B2 (en) 2005-07-29 2014-12-30 Gpb Scientific, Llc Devices and methods for enrichment and alteration of circulating tumor cells and other particles
JP4968577B2 (en) * 2006-04-11 2012-07-04 エフ．ホフマン−ラ ロシュ アーゲー Rapid measurement method of cytokeratin 19 (CK19) mRNA, and primer and probe therefor
US20080050739A1 (en) 2006-06-14 2008-02-28 Roland Stoughton Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
EP2589668A1 (en) 2006-06-14 2013-05-08 Verinata Health, Inc Rare cell analysis using sample splitting and DNA tags
US8137912B2 (en) 2006-06-14 2012-03-20 The General Hospital Corporation Methods for the diagnosis of fetal abnormalities
US20080070792A1 (en) 2006-06-14 2008-03-20 Roland Stoughton Use of highly parallel snp genotyping for fetal diagnosis
WO2010096036A2 (en) * 2008-05-14 2010-08-26 Millennium Pharmaceuticals, Inc. Methods and kits for monitoring the effects of immunomodulators on adaptive immunity
SI2334812T1 (en) 2008-09-20 2017-05-31 The Board of Trustees of the Leland Stanford Junior University Office of the General Counsel Building 170 Noninvasive diagnosis of fetal aneuploidy by sequencing
KR101371127B1 (en) * 2010-11-23 2014-03-10 한양대학교 산학협력단 A KRT19 Stabilizing HER2 and the Use thereof
EP3733870A3 (en) 2011-01-14 2021-01-27 Life Technologies Corporation Methods for identification and quantification of mirnas
KR101320633B1 (en) * 2011-05-25 2013-10-30 엠앤디 (주) Method of providing information for diagnosis of cancer using quantitative realtime PCR and diagnostic kit comprising thereof
GB2524948A (en) * 2014-03-07 2015-10-14 Oxford Gene Technology Operations Ltd Detecting Increase or Decrease in the Amount of a Nucleic Acid having a Sequence of Interest

Family Cites Families (112)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA464874A (en) 1950-05-02 Toledo Scale Company Valve connector device
US2004219A (en) 1931-11-25 1935-06-11 Textile Machine Works Automatically variable tensioning device for draw-off reels
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (en) 1984-07-19 1989-02-17 Centre Nat Rech Scient NOVEL OLIGONUCLEOTIDES, THEIR PREPARATION PROCESS AND THEIR APPLICATIONS AS MEDIATORS IN DEVELOPING THE EFFECTS OF INTERFERONS
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (en) 1985-01-08 1987-04-03 Pasteur Institut NOVEL ADENOSINE DERIVATIVE NUCLEOSIDES, THEIR PREPARATION AND THEIR BIOLOGICAL APPLICATIONS
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
EP0215942B1 (en) 1985-03-15 1995-07-12 Antivirals Inc. Polynucleotide assay reagent and method
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
JP2828642B2 (en) 1987-06-24 1998-11-25 ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン Nucleoside derivative
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
JPH03503894A (en) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション Oligonucleotide N-alkylphosphoramidate
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
EP0942000B1 (en) 1989-10-24 2004-06-23 Isis Pharmaceuticals, Inc. 2'-Modified oligonucleotides
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
ES2116977T3 (en) 1990-05-11 1998-08-01 Microprobe Corp SOLID SUPPORTS FOR NUCLEIC ACID HYBRIDIZATION TESTS AND METHODS TO IMMOBILIZE OLIGONUCLEOTIDES IN A COVALENT WAY.
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
BR9106702A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Inc ANALOG OF OLIGONUCLEOTIDEOS AND PROCESSES TO MODULATE THE PRODUCTION OF A PROTEIN BY AN ORGANISM AND TO TREAT AN ORGANISM
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
IL113519A (en) 1990-08-03 1997-11-20 Sterling Winthrop Inc Oligonucleoside sequences of from about 6 to about 200 bases having a three atom internucleoside linkage, their preparation and pharmaceutical compositions for inhibiting gene expression containing said oligonucleosides
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
CA2092002A1 (en) 1990-09-20 1992-03-21 Mark Matteucci Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
DE59208572D1 (en) 1991-10-17 1997-07-10 Ciba Geigy Ag Bicyclic nucleosides, oligonucleotides, processes for their preparation and intermediates
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
JP3739785B2 (en) 1991-11-26 2006-01-25 アイシス ファーマシューティカルズ，インコーポレイティド Enhanced triple and double helix shaping using oligomers containing modified pyrimidines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
FR2687679B1 (en) 1992-02-05 1994-10-28 Centre Nat Rech Scient OLIGOTHIONUCLEOTIDES.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (en) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclic nucleosides having bicyclic rings, oligonucleotides therefrom, process for their preparation, their use and intermediates
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
CA2159631A1 (en) 1993-03-30 1994-10-13 Sanofi Acyclic nucleoside analogs and oligonucleotide sequences containing them
WO1994022891A1 (en) 1993-03-31 1994-10-13 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (en) 1993-04-10 1994-10-13 Degussa Coated sodium percarbonate particles, process for their preparation and detergent, cleaning and bleaching compositions containing them
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5446677A (en) 1994-04-28 1995-08-29 Johnson Service Company Diagnostic system for use in an environment control network
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
GB9423912D0 (en) * 1994-11-26 1995-01-11 Imp Cancer Res Tech Detecting tumours
US5792747A (en) 1995-01-24 1998-08-11 The Administrators Of The Tulane Educational Fund Highly potent agonists of growth hormone releasing hormone
US6218529B1 (en) * 1995-07-31 2001-04-17 Urocor, Inc. Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer
JP3756313B2 (en) 1997-03-07 2006-03-15 武 今西 Novel bicyclonucleosides and oligonucleotide analogues
IL135000A0 (en) 1997-09-12 2001-05-20 Exiqon As Bi- and tri-cyclic nucleoside, nucleotide and oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
KR100782896B1 (en) 1999-05-04 2007-12-06 엑시콘 에이/에스 L-Ribo-LNA analogues
JP4392163B2 (en) 2000-06-21 2009-12-24 日立化成工業株式会社 Genetic marker for lung cancer
EP1446412B1 (en) 2001-09-04 2012-03-07 Exiqon A/S Novel lna compositions and uses thereof
KR100445560B1 (en) * 2001-10-31 2004-08-21 (주)바이오넥스 Method of manufacturing kit for isolating nucleic acids or biological materials, kit manufactured by the method, and apparatus using the kit
US7026120B2 (en) 2002-04-15 2006-04-11 Abbott Laboratories Probes for detecting tumor cells
EP1510587B1 (en) * 2002-05-21 2011-07-13 Sysmex Corporation Nucleic acid amplification primers for detecting cytokeratins and examination method with the use of the primers
DE60332948D1 (en) * 2002-07-19 2010-07-22 Althea Technologies Inc STRATEGIES FOR GENE EXPRESSION ANALYSIS
US20040022764A1 (en) 2002-07-31 2004-02-05 Hanan Polansky Inhibition of microcompetition with a foreign polynucleotide as treatment of chronic disease
US20040048258A1 (en) 2002-09-10 2004-03-11 Windber Research Institute Multiple-gene diagnostic probes and assay kits and method for the assessment of multiple markers for breast cancer prognosis
US20040219565A1 (en) * 2002-10-21 2004-11-04 Sakari Kauppinen Oligonucleotides useful for detecting and analyzing nucleic acids of interest
US7267950B2 (en) * 2003-05-01 2007-09-11 Veridex, Lcc Rapid extraction of RNA from cells and tissues
DE602004015037D1 (en) * 2003-05-01 2008-08-28 Veridex Llc Intraoperative lymph node test
ATE548447T1 (en) * 2004-01-14 2012-03-15 Novahep Ab HUMAN HEPATIC PROGRESSOR CELLS AND METHOD OF USE THEREOF

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US9593374B2 (en) 2017-03-14
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US20140057265A1 (en) 2014-02-27
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