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`US008088575B2
`
`c12) United States Patent
`Ju et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 8,088,575 B2
`Jan.3,2012
`
`(54) MASSIVE PARALLEL METHOD FOR
`DECODING DNA AND RNA
`
`(75)
`
`Inventors: Jingyue Ju, Englewood Cliffs, NJ (US);
`Zengmin Li, New York, NY (US); John
`Robert Edwards, New York, NY (US);
`Yasuhiro Itagaki, New York, NY (US)
`
`(73) Assignee: The Trustees of Columbia University
`in the City of New York, New York, NY
`(US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`(21) Appl. No.: 12/804,284
`
`(22) Filed:
`
`Jul. 19, 2010
`
`(65)
`
`Prior Publication Data
`
`US 2010/0317012Al
`
`Dec. 16, 2010
`
`(58) Field of Classification Search ................. 536/23.1,
`536/24.3, 25.3, 26.6; 435/6
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`4,711,955 A
`12/1987 Ward et al.
`4,772,691 A
`9/1988 Herman
`4,824,775 A
`4/1989 Dattagupta
`4,863,849 A
`9/1989 Melamede
`5,043,272 A
`8/1991 Hartley
`6/1992 Urdea
`5,118,605 A
`5,174,962 A
`12/1992 Brennan
`5,175,269 A
`12/1992 Stavrianopoulos et al.
`5,302,509 A
`4/1994 Cheeseman
`(Continued)
`
`DE
`
`FOREIGN PATENT DOCUMENTS
`4141178
`6/1993
`(Continued)
`
`OTHER PUBLICATIONS
`
`Related U.S. Application Data
`
`U.S. Appl. No. 90/008,149, filed Aug. 4, 2006, Gitten.
`
`(60) Continuation of application No. 11/810,509, filed on
`Jun. 5, 2007, now Pat. No. 7,790,869, which is a
`continuation of application No. 10/702,203, filed on
`Nov. 4, 2003, now Pat. No. 7,345,159, which is a
`division of application No. 09/972,364, filed on Oct. 5,
`2001, now Pat. No. 6,664,079, which
`is a
`continuation-in-part of application No. 09/684,670,
`filed on Oct. 6, 2000, now abandoned.
`
`(60) Provisional application No. 60/300,894, filed on Jun.
`26, 2001.
`
`(51)
`
`Int. Cl.
`C12Q 1168
`(2006.01)
`(2006.01)
`C07H 21/00
`(2006.01)
`C07H 21/02
`(52) U.S. Cl. ......... 435/6; 536/23.1; 536/24.3; 536/25.3;
`536/26.6
`
`(Continued)
`
`Primary Examiner -
`Jezia Riley
`(74) Attorney, Agent, or Firm -John P. White; Cooper &
`DunhamLLP
`
`ABSTRACT
`(57)
`This invention provides methods for attaching a nucleic acid
`to a solid surface and for sequencing nucleic acid by detecting
`the identity of each nucleotide analogue after the nucleotide
`analogue is incorporated into a growing strand of DNA in a
`polymerase reaction. The invention also provides nucleotide
`analogues which comprise unique labels attached to the
`nucleotide analogue through a cleavable linker, and a cleav(cid:173)
`able chemical group to cap the -OH group at the 3'-position
`of the deoxyribose.
`
`6 Claims, 28 Drawing Sheets
`
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`readlhesequenee
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`ISA(l,R),dC(2,R).
`aG(3,A),dT(4,A)
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`
`Page 1
`
`Illumina Ex. 1015
`IPR Petition - USP 10,435,742
`
`

`

`U.S. PATENT DOCUMENTS
`5,308,990 A
`5/1994 Takahashi et al.
`5,328,824 A
`7/1994 Ward et al.
`5,332,666 A
`7/1994 Prober et al.
`5,436,143 A
`7/1995 Hyman
`5,437,975 A
`8/1995 McClelland et al.
`5,449,767 A
`9/1995 Ward et al.
`5,476,928 A
`12/1995 Ward et al.
`5,516,664 A
`5/1996 Hyman
`5,534,424 A
`7/1996 Uhlen et al.
`5,547,839 A
`8/1996 Dower et al.
`5,547,859 A
`8/1996 Goodman et al.
`5,556,748 A
`9/1996 Douglas
`5,599,675 A
`2/1997 Brenner
`5,602,000 A
`2/1997 Hyman
`5,637,469 A
`6/1997 Wilding et al.
`5,654,419 A
`8/1997 Mathies
`5,658,736 A
`8/1997 Wong
`5,709,999 A
`1/1998 Shattuck et al.
`5,728,528 A
`3/1998 Mathies
`5,763,594 A
`6/1998 Hiatt et al.
`5,770,365 A
`6/1998 Lane et al.
`5,770,367 A
`6/1998 Southern
`5,789,167 A
`8/1998 Konrad
`5,798,210 A
`8/1998 Canard et al.
`5,804,386 A
`9/1998 Ju et al.
`5,808,045 A
`9/1998 Hiatt et al.
`5,814,454 A
`9/1998 Ju et al.
`5,821,356 A
`10/1998 Khan et al.
`5,834,203 A
`11/1998 Katzir
`5,849,542 A
`12/1998 Reeve et al.
`5,853,992 A
`12/1998 Glazer
`5,856,104 A
`1/1999 Chee et al.
`5,869,255 A
`2/1999 Mathies
`5,872,244 A
`2/1999 Hiatt et al.
`5,876,936 A
`3/1999 Ju et al.
`5,885,775 A
`3/1999 Haff et al.
`5,908,755 A
`6/1999 Kumar et al.
`5,945,283 A
`8/1999 Kwok
`5,952,180 A
`9/1999 Ju et al.
`5,962,228 A
`10/1999 Brenner
`6,001,566 A
`12/1999 Canard et al.
`6,001,611 A
`12/1999 Will
`6,008,379 A
`12/1999 Benson et al.
`6,028,190 A
`2/2000 Mathies
`6,046,005 A
`4/2000 Ju et al.
`6,074,823 A
`6/2000 Koster
`6,087,095 A
`7/2000 Rosenthal et al.
`6,136,543 A
`10/2000 Anazawa et al.
`6,175,107 Bl
`1/2001 Juvinall
`6,197,557 Bl
`3/2001 Makarov et al.
`6,207,831 Bl
`3/2001 Auer et al.
`6,210,891 Bl
`4/2001 Nyren et al.
`6,214,987 Bl
`4/2001 Hiatt et al.
`6,218,118 Bl
`4/2001 Sampson
`6,218,530 Bl
`4/2001 Rothschild et al.
`6,221,592 Bl
`4/2001 Schwartz et al.
`6,232,465 Bl
`5/2001 Hiatt et al.
`6,242,193 Bl
`6/2001 Anazawa et al.
`6,245,507 Bl
`6/2001 Bogdanov
`6,255,475 Bl
`7/2001 Kwiatkowski
`6,274,320 Bl
`8/2001 Rothberg
`6,277,607 Bl
`8/2001 Tyagi et al.
`6,287,821 Bl
`9/2001 Shi et al.
`6,294,324 Bl
`9/2001 Bensimon et al.
`6,309,829 Bl
`10/2001 Livak et al.
`6,309,836 Bl
`10/2001 Kwiatkowski et al.
`6,312,893 Bl
`11/2001 Van Ness et al.
`6,316,230 Bl
`11/2001 Egholm
`6,361,940 Bl
`3/2002 Van Ness et al.
`6,380,378 Bl
`4/2002 Kitamura et al.
`6,524,829 Bl
`2/2003 Seeger et al.
`4/2003 O'Donnell
`6,555,349 Bl
`6,613,508 Bl
`9/2003 Ness et al.
`6,613,513 Bl
`9/2003 Paree et al.
`6,627,748 Bl
`9/2003 Ju et al.
`6,632,655 Bl
`10/2003 Mehta et al.
`6,639,088 B2
`10/2003 Kwiatkowski
`6,664,079 B2
`12/2003 Ju et al.
`
`US 8,088,575 B2
`Page 2
`
`6,664,399 Bl
`6,713,255 Bl
`6,780,591 B2
`6,787,308 B2
`6,818,395 Bl
`6,833,246 B2
`6,864,052 Bl
`6,911,345 B2
`6,934,636 Bl
`6,982,146 Bl
`7,037,687 B2
`7,056,661 B2
`7,056,666 B2
`7,057,026 B2
`7,057,031 B2
`7,074,597 B2
`7,078,499 B2
`7,105,300 B2
`7,329,496 B2
`7,345,159 B2
`7,414,116 B2
`7,427,673 B2
`7,459,275 B2
`7,566,537 B2
`7,622,279 B2
`7,635,578 B2
`7,713,698 B2
`2002/0012966 Al
`2002/0168642 Al
`2003/0008285 Al
`2003/0022225 Al
`2003/0027140 Al
`2003/0044871 Al
`2003/0054360 Al
`2003/0099972 Al
`2003/0166282 Al
`2003/0186256 Al
`2003/0190680 Al
`2003/0198982 Al
`2004/0014096 Al
`2004/0096825 Al
`2004/0185466 Al
`2005/0032081 Al
`2005/0239134 Al
`2006/0003352 Al
`2006/0057565 Al
`2006/0105461 Al
`2006/0240439 Al
`2006/0252938 Al
`2007/0166705 Al
`2007/0275387 Al
`2008/0131895 Al
`2008/0199868 Al
`2008/0319179 Al
`2009/0088332 Al
`
`12/2003 Sabesan
`3/2004 Makino eta!.
`8/2004 Williams et al.
`9/2004 Balasubramanian et al.
`11/2004 Quake et al.
`12/2004 Balasubramanian et al.
`3/2005 Drmanac et al.
`6/2005 Quake et al.
`8/2005 Skierczynski et al.
`1/2006 Schneider et al.
`5/2006 Williams et al.
`6/2006 Korlach et al.
`6/2006 Dower et al.
`6/2006 Barnes et al.
`6/2006 Olejnik et al.
`7/2006 Ju
`7/2006 Odedra et al.
`9/2006 Paree et al.
`2/2008 Dower et al.
`3/2008 Ju et al.
`8/2008 Milton et al.
`9/2008 Balasubramanian et al.
`12/2008 Dower et al.
`7/2009 Balasubramanian et al.
`11/2009 Ju
`12/2009 Ju
`5/2010 Ju
`1/2002 Shi et al.
`11/2002 Drukier
`1/2003 Fischer
`1/2003 Monforte et al.
`2/2003 Ju et al.
`3/2003 Cutsforth et al.
`3/2003 Gold et al.
`5/2003 Olejnik
`9/2003 Brown eta!.
`10/2003 Fischer et al.
`10/2003 Rothschild et al.
`10/2003 Seela et al.
`1/2004 Anderson et al.
`5/2004 Chenna et al.
`9/2004 Ju et al.
`2/2005 Ju et al.
`10/2005 Goren stein et al.
`1/2006 Lipkin et al.
`3/2006 Ju et al.
`5/2006 Tom-Moy et al.
`10/2006 Smith et al.
`11/2006 Sava et al.
`7/2007 Milton et al.
`11/2007 Ju
`6/2008 Ju et al.
`8/2008 Ju et al.
`12/2008 Ju et al.
`4/2009 Ju et al.
`
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`
`FOREIGN PATENT DOCUMENTS
`0992511 A
`4/2000
`0995804
`4/2000
`1182267
`2/2002
`1291354
`3/2003
`0808320
`4/2003
`1337541
`3/2007
`1218391
`4/2007
`1790736
`5/2007
`WO 89/09282
`10/1989
`WO 90/13666
`11/1990
`WO 91/06678
`5/1991
`WO 92/10587
`6/1992
`WO 93/05183
`3/1993
`WO 93/21340
`10/1993
`WO 94/14972
`7 /1994
`WO 96/07669
`3/1996
`WO 96/23807
`8/1996
`WO 96/27025
`9/1996
`WO 97/08183
`3/1997
`WO97/27317
`7 /1997
`WO 97/35033
`9/1997
`WO 98/30720
`7 /1998
`
`Page 2
`
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`US 8,088,575 B2
`Page 3
`
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`
`WO 98/44151
`WO 99/05315
`WO 00/02895
`WO 00/06770
`WO 00/09753
`WO 00/15844
`WO 00/18956
`WO 00/21974
`WO 00/50172
`WO 00/50642
`WO 00/53805
`WO 00/53812
`WO 00/70073
`WO 01/16375
`WO 01/23610
`WO 01/25247
`WO 01/27625 A
`WO 01/32930
`WO 01/57248
`WO 01/57249
`WO 01/92284
`WO 02/02813
`WO 02/22883 Al
`WO 02/29003
`WO 02/072892
`WO 02/079519 Al
`WO 02/088381
`WO 02/088382
`WO 03/002767
`WO 03/020968
`WO 03/048178
`WO 03/048387
`WO 03/085135
`WO 2004/007773
`WO 2004/055160
`WO 2004/018493
`WO 2004/018497
`WO 2004/108497
`WO 2005/084367
`WO 2006/073436
`WO 2007 /002204
`WO 2007/053702
`WO 2007/053719
`WO/2007 /062105
`WO 2008/069973
`WO 99/57321
`
`10/1998
`2/1999
`1/2000
`2/2000
`2/2000
`3/2000
`4/2000
`4/2000
`8/2000
`8/2000
`9/2000
`9/2000
`11/2000
`3/2001
`4/2001
`4/2001
`4/2001
`5/2001
`8/2001
`8/2001
`12/2001
`1/2002
`3/2002
`4/2002
`9/2002
`10/2002
`11/2002
`11/2002
`1/2003
`3/2003
`6/2003
`6/2003
`10/2003
`1/2004
`1/2004
`3/2004
`3/2004
`4/2004
`9/2005
`7/2006
`1/2007
`5/2007
`5/2007
`5/2007
`6/2008
`11/2009
`
`OTHER PUBLICATIONS
`
`U.S. Appl. No. 90/008,152, filed Aug. 3, 2006, Girten.
`Arbo et al. ( 1993) "Solid Phase Synthesis of Protected Peptides
`Using New Cobalt (Ill) Amine Linkers," Int. J. Petide.Protein Res.
`42: 138-154.
`Axelrod, V.D. et al. (1978) "Specific termination of RNA polymerase
`synthesis as a method of RNA and DNA sequencing" Nucleic Acids
`Res. 5(10) :3549-3563.
`Badman, E. R. et al. (2000) "A Parallel Miniature Cylindrical Ion
`Trap Array," Anal. Chem. (2000) 72:3291-3297.
`Badman, E.R. et al. (2000) "Cylnidrical Ion Trap Array with Mass
`Selection by Variation in Trap Dimensions," Anal. Chem. 72:5079-
`5086.
`Burgess, K. et al (1997) "Photolytic Mass Laddering for Fast Char(cid:173)
`acterization of Oligomores on Single Resin Beads," J. Org. Chem.
`62: 5662-5663.
`(1993)
`and Glazer, A.N.
`Benson, S.C., Mathies, R.A.,
`"Heterodimeric DNA-binding dyes designed ... application of the
`DNA complexes," Nucleic Acids REs. 21 :5720-5726.
`Benson, S.C., Singh, P., and Glazer, A.N. (1993) "Heterodimeric
`DNA-binding dyes designed ... spectroscopic properties," Nucleic
`Acids REs. 21:5727-5735.
`Bergseid M., Baytan A.R., Wiley J.P., Ankener W.M., Stolowitz,
`Hughs K.A., and Chestnut J.D. (2000) "Small-molecule base .
`proteins," BioTechniques 29:1126-1133.
`Buck, G.A. et al. (1999) "Design Strategies and Performance of
`Custom DNA Sequencing Primers," Bio Techniques 27(3):528-536.
`Buschmann et al.
`(1999) "The Complex Formation of A,
`m-Dicarboxylic Acidsd and A, m-Diols with Cucurbituril and
`a-Cyclodextrin," Acata Chim. Slov. 46 (3):405-411.
`
`Canard, B. et al. (1995) "Catalytic editing properties of DNA
`polymerases," Proc. Natl. Acad. Sci. USA 92:10859-10863.
`Caruthers, M.H. (1985) "Gene synthesis machines: DNA chemistry
`and its uses," Science 230:281-285.
`Chee, M. et al. (1996) "Accessing genetic information with high
`density DNA arrays," Science 274:610-614.
`Chen, X. And Kwok, P.-Y. ( 1997) "Template-directed dye-terminator
`incorporation (TDI) assay: a homogeneous DNA diagnostic
`transfer," Nucleic Acids Res. 25:347-353.
`Chiu, N. H., Tang, K., Yip, P., Braun, A., Koster, H., and Cantor, C.R.
`(2000) "Mass spectrometry of single-stranded ... sequence," Nucleic
`Acids Res. 28:E31.
`Edwards, J. et al. (2001) "DNA sequencing using biotinylated
`dideoxynucleotides and mass spectrometry," Nucleic Acids Res.
`29(21) 1041-1046.
`Elango, N. et al. (1983) "Amino Acid Sequence of Human Respira(cid:173)
`tory Syncytial Virus Nucleocapsid Protein." Nucleic Acids Research
`l 1(17):5941-5951.
`Fallahpour (2000) "Photochemical and Thermal reactions of Azido(cid:173)
`Oligopyridines: Diazepinones, a New Class of Metal-Complex
`Ligands," Helvetica Chimica Acta. 83:384-393.
`Fei, Z. et al. (1998) "MALDI-TOF mass spectrometric typing of
`single nucleotide polymorphisms with mass-tagged ddNTPs,"
`Nucleic Acids Research 26(11):2827-2828.
`Fu, D.J., et al (1998) "Sequencing exons 5 to 8 of the p53 gene by
`MALDI-TOF mass spectrometry," Nat. Biotechnol, 16:381-384.
`Griffin, T.J. et al. ( 1999) "Direct Genetic Analysis by Matrix-Assisted
`Laser Desorption/Ionization Mass Spectrometry," Proc. Nat. Acad.
`Sci. USA 96:6301-6306.
`Hacia J.G., Edgemon K., Sun B., Stern D., Fodor S.A., and Collins
`F.S. (1998) "Two Color Hybridization Analysis Using High .
`Transfer Dyes," Nucleic Acids Res. 26:3865-6.
`Haff L.A.; et al. ( 1997) "Multiplex Genotyping of PCR Products with
`Mass Tag-Labeled Primers," Nucleic Acids Res. 25(18):3749-3750.
`Hafliger, D. et al. (1997) "Semi-nested RT-PCR Systems for Small
`Round Structured Viruses and Detection ... Seafood," International
`Journal of Food Microbiology, 37:27-36.
`Renner, W.D. et al. (1983) "Enzyme Action at 3' Termini oflonizing
`Radiation-Induced DNA Strand Breaks,"
`J. Biol. Chem.
`258(24): 15198-15205.
`Hultman et al. (1989) "Direct Solid Phase Sequencing of Genomic
`and Plasmid DNA Using Magnetic Beads as Solid Support," Nucleic
`Acids Research 17(3):4937-4946.
`Hyman, E.D., (1988) "Anew method of sequencing DNA," Analyti(cid:173)
`cal Biochemistry 174:423-436.
`Ireland, R.E. And Varney, M.D. (1986) "Approach to the total syn(cid:173)
`thesis of chlorothricolide synthesis of ( +/)-19.20-dihydro-24-O- .
`ethyl carbonate," J. Org. Chem. 51:635-648.
`Kamal, A., Laxman, E., and Rao, N.V. (1999) "A mild and rapid
`regeneration of alcohols from their allylic ethers ... iodide," Tetra(cid:173)
`hedron Lett 40:371-372.
`Ikeda, K. et al. (1995) "A Non-Radioactive DNA Sequencing Method
`Using Biotinylated Dideoxynucleoside Triphosphates and Delta
`TTH DNA Polymerase," DNA Research 2(31):225-227.
`Jiang-Baucom, P. et al. (1997) "DNA Typing of Human Leukocyte
`Antigen Sequence Polymorphisms by Peptide Nucleic Acid Probes
`and ... Spectrometry," Anal. Chem. 69:4894-4896.
`Jingyue Ju, et al. (1996) "Cassette labeling for facile construction of
`energy transfer fluorescent primers," Nuc. Acids Res. 24(6): 1144-
`1148.
`Ju J., Glazer, A.N., and Mathies, R.A. ( 1996) "Energy transfer prim(cid:173)
`ers: A new fluorescence labeling paradigm for DNA sequencing and
`analysis," Nature Medicine 2: 246-249.
`Ju J., Ruan C., Fuller, C.W., Glazer, A.N., and Mathies, R.A. (1995)
`"Fluorescence energy transfer dye-labeled primers for ... analysis,"
`Proc. Natl. Acad. Sci. USA 92:4347-4351.
`Jurinke, C., van de Boom, D., Collazo, V., Luchow, A., Jacob, A., and
`Koster H. ( 1997) "Recovery of nucleic acids from immobilized .
`spectrometry," Anal. Chem 69:904-910.
`Kim, S. et al. (2003) "Multiplex Genotyping of the Human
`132-adrenergic Receptor Gene Using Solid-phase Capturable .
`Spectrometry," Analytical Biochemistry 316 :251-25 8.
`
`Page 3
`
`

`

`US 8,088,575 B2
`Page 4
`
`Kim Sobin et al. (2002) "Solid Phase Capturable Dideoxynucleotides
`for Multiplex Genotyping Using Mass Spectrometry," Nucleic Acids
`Research 30(16):e85. l-e85.6.
`Kokoris, M. et al. (2000) High-throughput SNP Genotyping With the
`Masscode System, Molecular Diagnosis 5(4):329-340.
`Kolb et al. (2001) "Click Chemistry: Diverse Chemical Function
`From a Few Good Reactions," Angew. Chem. Int. Ed. 40:2004-2021.
`Kraevskii, A.A. et al. (1987) "Substrate Inhibitors of DNA
`Biosynthesis," Molecular Biology 21 :25-29.
`Lee, L.G., et al. (1992) "DNA sequencing with dye labeled termina(cid:173)
`tors and T7 DNA polymerase effect of dyes and dNTPs ... frag(cid:173)
`ments" Nucleic Acids Res. 20:2471-2483.
`Lee, L.G. et al, (1997) "New energy transfer dyes for DNA sequenc(cid:173)
`ing" Nucleic Acids Res. 25:2816-2822.
`Lewis et al., (2002) "Click Chemistry in Situ: Acetylcholinesterase as
`a Reaction Vessel for Array of Building Blocks," Angew. Chem. Int.
`Ed. 41(6):1053-1057.
`Leroy, E.M. et al. (2000) "Diagnosis of Ebola Haemorrhagic Fever by
`RT-PCR in an Epidemic Setting," Journal of Medical Virology
`60:463-467.
`Li, J. (1999) "Single Oligonucleotide Polymorphism Determination
`Using Primer Extension and Time-of-Flight Mass Spectrometry,"
`Electrophoresis 20:1258-1265.
`Liu, H. et al. (2000) "Development of Multichannel Devices with an
`Array of Electrospray Tips for High-Throughput Mass Spectrom(cid:173)
`etry," Anal. Chem. 72:3303-3310.
`Lyamichev, A. et al. (1999) "Polymorphism Identification and Quan(cid:173)
`titative Detection of Genomic DNA by Invasive Cleavage of
`Oligonucleotide Probes," Nat. Biotech 17:292-296.
`Metzker, M.L. et al. ( 1994) "Termination of DNA synthesis by novel
`3' modified deoxyribonucleoside 5' triphosphates," Nucleic Acids
`Res. 22: 4259-4267.
`Monforte, J.A. and Becker, C.H. (1997) "High-throughput DNA
`analysis by time-of-flight mass spectrometry," Nat. Med. 3(3):360-
`362.
`Olejnik, J. et al. (1999) "Photocleavable peptide DNA conjugates:
`synthesis and applications to DNA analysis using MALDI MS,"
`Nucleic Acids Res. 27 :4626-4631.
`Olejnik, J. et al. ( 1995) "Photocleavable biotin derivatives: a versatile
`approach for the isolation of biomolecules," Proc. Natl. Acad. Sci.
`USA. 92:7590-7594.
`Pelletier, H. et al. (1994) "Structures of ternary complexes ofratDNA
`polymerase fl, a DNA template-primer, and ddCTP," Science
`264:1891-1903.
`Prober, J.M. et al.( 1987) "A, system for rapid DNA sequencing with
`fluorescent
`chain-terminating
`dideoxynucleotides,"
`Science
`238:336-341.
`Ronaghi, M., Uhlen, M., and Nyren, P. ( 1998) "A sequencing Method
`based on real-time pyrophosphate," Science 281:364-365.
`Rosenblum, B.B. et al. (1997) "New dye-labeled terminators for
`improved DNA sequencing patterns," Nucleic Acids Res. 25:4500-
`4504.
`Roskey, M.T., Juhasz, P., Smirnov, LP., Takach, E.J., Martin, S.A.,
`and Haff, L.A. (1996) "DNA sequencing ... mass spectrometry,"
`Proc. Natl. Acad. Sci. USA. 93:4724-4729.
`Ross, P. et al. (1998) High Level Multiplex Genotyping by MALDI(cid:173)
`TOF Mass Spectrometry. Nat. Biotech 16:1347-1351.
`Ross, P.L. et al. (1997) "Discrimination of Single-Nucleotide
`Polymorphisms in Human DNA Using Peptide Nucleic Acid
`Probes ... Spectrometry," Anal. Chem. 69:4197-4202.
`Saxon, E. and Bertozzi, C.R. (2000) "Cell surface engineering by a
`modified Staudinger reaction," Science 287:2007-2010.
`Schena, M., Shalon, D. and Davis, R. Brown P.O. (1995) "Quantita(cid:173)
`tive monitoring of gene expression patterns with a cDNA microar(cid:173)
`ray," Science 270: 467-470.
`Seo et al. (2003) "Click Chemistry to Construct Fluorescent
`Oligonucleotides for DNA Sequencing," J. Org. Chem. 68:609.
`Speicher, M.R., Ballard, S.G., and Ward, D.C. (1996) "Karyotyping
`human chromosomes by combinatorial multi-fluor FISH," Nature
`Genetics 12: 368-375.
`Stoerker, J. et al. (2000) "Rapid Genotyping by MALDI-monitored(cid:173)
`nuclease selection from probe Libraries," Nat. Biotech 18: 1213-
`1216.
`
`Tang, K., Fu, D.J., Julien, D., Braun, A., Cantor, C.R., and Koster, H.
`(1999) "Chip-based genotyping by mass spectrometry," Proc. Natl.
`Acad. Sci. USA. 96: 10016-10020.
`Tong, X. and Smith, L.M. (1992) "Solid-Phase Method for the Puri(cid:173)
`fication of DNA Sequencing Reactions," Anal. Chem. 64:2672-2677.
`Wendy, Jen. et al. (2000) "New Strategies for Organic Catalysis: The
`First Enantioselective Orgacnocatalytic 1,3-Dipolar Cycloaddition,"
`J. Am. Chem. Soc. 122:9874-9875.
`Welch MB, Burgess K, (1999) "Synthesis of fluorescent, photolabile
`3'-O-protected nucleoside triphosphates ... scheme," Nucleosides
`and Nucleotides 18:197-201.
`Woolley, A. T. et al. (1997) "High-Speed DNA Genotyping Using
`Microfabricated Capillary Array Electrophoresis Chips," Anal.
`Chem. 69:2181-2186.
`International Preliminary Examination Report issued on Mar. 18,
`2005 in connection with PCT/US03/21818.
`International Preliminary Examination Report issued on Jun. 13,
`2003 in connection with PCT/US0l/31243.
`International Preliminary Examination Report issued on Feb. 25,
`2003 in connection with PCT/US0l/28967.
`International Preliminary Examination Report issued on Mar. 17,
`2003 in connection with PCT/US02/09752.
`International Preliminary-Report on Patentability issued on Sep. 5,
`2006 in connection with PCT/US05/006960.
`International Search Report issued May 13, 2002 in connection with
`PCT/US0l/31243.
`International Search Report issued Jan. 23, 2002 in connection with
`PCT/US0l/28967.
`International Search Report issued Sep. 18, 2002 in connection with
`PCT/US02/09752.
`International Search Report issued Sep. 26, 2003 in connection with
`PCT/US03/21818.
`International Search Report issued Jun. 8, 2004 in connection with
`PCT/US03/39354.
`International Search Report issued Nov. 4, 2005 in connection with
`PCT/US05/06960.
`International Search Report issued Dec. 15, 2006 in connection with
`PCT/US05/13883.
`Partial European Search Report issued Apr. 26, 2007 in connection
`with European Patent Application No. 07004522.4.
`Supplementary European Search Report issued Feb. 16, 2004 in
`connection with European Patent Application No. 01 97 7 533.
`Supplementary European Search Report-issued Feb. 9, 2007 in con(cid:173)
`nection with European Patent Application No. 03 76 4568.6.
`Supplementary European Search Report issued May 25, 2005 in
`connection with European Patent Application No. 02 72 8606.1.
`Supplementary European Search Report issued Jun. 7, 2005 in con(cid:173)
`nection with European Patent Application No.01 96 8905.
`Supplementary European Search Report issued Sep. 9, 2008 in con(cid:173)
`nection with PCT International Application No. PCT/US05/06960.
`Written Opinion of the International Searching Authority issued Oct.
`27, 2005 in connection with PCT/US05/06960.
`Written Opinion of the International Searching Authority issued Dec.
`15, 2006 in connection with PCT/US05/13883.
`Li et al. (2003) "A photocleavable Fluorescent Nucleotide for DNA
`Sequencing and Analysis," PNAS 100(2):414-419.
`Meng et al. (2006) "Design and Synthesis of a Photocleavable Fluo(cid:173)
`rescent ... Sequencing by Synthesis," J. Org. Chem 71:3248-3252.
`Ruparel et al. (2005) "Design and Synthesis of a 3'-O-Allyl
`Photocleavable Fluorescent Nucleotide
`as
`a Reversible
`Terminator ... by Synthesis," PNAS 102(17):5932-5937.
`Seo et al. (2004) "Photocleavable Fluorescent Nucleotides for DNA
`Sequencing on a Chip Constructed by Site-Specific Coupling Chem(cid:173)
`istry," PNAS 101(15):5488-5493.
`Seo et al. (2004) "Four-Color DNA Sequencing by Synthesis on a
`Chip Using Photocleavable Fluorescent Nucleotides," PNAS
`102(17):5926-593 l.
`Tuncel et al. ( 1999) "Catalytically Self-Threading Polyrotaxanes,"
`Chem. Comm. 1509-1510.
`Kurata et al., Fluorescent quenching-based quantitative detection of
`specific DNA/RNA using BODIPY® FL-labeled probe of primer,
`Nucleic Acids ... p. e34 (2001 ).
`
`Page 4
`
`

`

`US 8,088,575 B2
`Page 5
`
`Welch et al., Synthesis ofNucleosides Designed for Combinatorial
`DNA Sequencing, Chemistry, European Journal, 5:951-960 (1999).
`Wada et al., 2-(Azidomethyl)benzoyl as a new protecting group in
`nucleosides, Tetrahedron Letters, 42:1069-1072 (2001).
`Sarfati et al., Synthesis of fluorescent derivatives of 3'-O-(6-
`aminohexanoyl)-pyrimidine nucleosides 5'triphosphates ... tagged
`atC-3', JCS Perkin Trans, 1163-1171 (1995).
`Rasolonjatovo et al., 6-N-
`(N-Methylanthranylamido)-4-Oxo(cid:173)
`Hexanoic Acid: A New Fluorescent Protecting Group Applicable.
`Nucleotides, 17 :2021-2025 ( 1998).
`Marquez et al., Selective Fluorescence Quenching of 2,3-
`Diazabicyclo[2.2.2] oct-2-ene by Nucleotides, Organic Letters,
`5:3911-3914 (2003).
`Nazarenko et al., Effect of primary and secondary structure of
`oligodeoxyribonucleotides on the fluorescent properties of conju(cid:173)
`gated dyes, Nucleic Acids Research, 30:2089-2095.
`Kvam et al., Characterization of singlet oxygen-induced guanine
`residue damage after photochemical treatment of free .
`. DNA,
`Biochemica et Biophysica Acta., 1217:9-15 (1994).
`Crespo-Hernandez et al., Part 1. Photochemical and Photophysical
`. Photobiology,
`Studies of Guanine Derivatives: Intermediates .
`71(5):534-543 (2000).
`314. Buschmann et al., Spectroscopic Study and Evaluation of Red(cid:173)
`Absorbing Fluorescent Dyes, Bioconjugate Chem., 14:195-204
`(2003).
`Torimura et al., Fluorescence-Quenching Phenomenon by Photo
`induced Electron Transfer between a Fluorescent Dye and
`Nucleotide Base, Analytical Sciences, 17:155-160 (2001).
`Markiewicz et al., Anew method of synthesis of fluorescently labeled
`oligonucleotides and their application in DNA sequencing, Nucleic
`Acids Research, 25 :3672-3690 ( 1997).
`Maier et al., Synthesis and Properties of New Fluorescein-Labeled
`Oligonucleotides; Nucleosides, Nucleotides, and Nucleic Acids
`14:961-965 (1995).
`Bergmann et al., Ally! As Internucleotide Protecting Group in DNA
`Synthesis to be Cleaved Off by Ammonia, Tetrahedron, 51:6971-
`6976 (1995).
`Guibe, Allylic Protecting Groups and Their Use in a Complex Envi(cid:173)
`ronment Part I: Allylic Protection of Alcohols, Tetrahedron,
`53: 13509-13556 (1997).
`Guibe, Allylic Protecting Groups and Their Use in a Complex Envi(cid:173)
`ronment Part II: Allylic Protecting ... Methodology, Tetrahedron,
`54:2967-3042 (1998).
`relative stability of ally! ether,
`Kloosterrnan et al., The
`allyloxycarbonyLester and prop-2 enylidene acetal ... Palladium
`catalysts, Tetrahedron Letters, 26:5045-5048 (1985).
`Kitamura et al., (P(C6H5)3)CpRu+Catalyzed Deprotection of Ally!
`Carboxylic Esters, J. Org. Chem., 67:4975-4977 (2002).
`Hayakawa et al., O-Allyl Protection of Guanine and Thymine Resi(cid:173)
`dues in Oligodeoxyribonucleotides, J. Org. Chem., 58:5551-5555
`(1993).
`Veeneman et al., An Efficient Approach to the Synthesis of
`Thymidine Derivatives Containing Phosphate-lsoteric Methylene
`Acetyl Linkages, Tetrahedron, 47:1547-1562 (1991).
`Zavgorodny et al., 1-Alkylthioalkylation of Nucleoside Hydroxl
`Functions and Its Synthetic Application: A New Versatile Method
`in ... Tetrahedron Letters, 32:7593-7596 (1991).
`Seeger, Single Molecule Fluorescence: High-Performance Molecu(cid:173)
`lar Diagnosis and Screening, Bio forum, Git Verlag, Darmstadt, DE
`vol. 21, No. (1998) (German text).
`Rao et al., Four Color FRET Dye Nucleotide Terminators for DNA
`Sequencing, Nucleosides, Nucleotides & Nucleic Acids, 20:673-
`676. (2001).
`J. Brunckova et al., Tetrahedron Letters, vol. 35, pp. 6619-6622
`(1994) (Exhibit 4).
`S. Nishino et al., Heteroatom Chemistry, vol. 2, pp. 187-196 (1991).
`M. Krecmerova, Coll. Czech. Chem. Commun., vol. 55, pp. 2521-
`2536 (1990).
`P.J.L.M. Quaedflieg et al., Tetretrahedron Letters, vol. 33, pp. 3081-
`3084 (1992).
`J. I. Yamashita et al., Chem Pharm. Bull., vol. 35, pp. 2373-2381
`(1987).
`
`S.G. Zavgorodnyet al., Nucleosides, Nucleotides and Nucleic Acids,
`19 (10-12), 1977-1991 (2000).
`Canard et al., DNA polymerase fluorescent substrates with reversible
`3'-tags, Gene, 148L 1-6 (1994).
`Hovinen et al., Synthesis of 3'-O-(m-Aminoalkoxymethyl)
`thymidine 5'-Triphosphates, Terminators of DNA Snythesis that
`Enable 3'-Labelling, J. Chem. Soc. Perkin Trans.,1:211-21.
`Nickel W, et al. ( 1992) "Interactions of azidothymidine triphosphate
`with the cellular DNA polymersases alpha ... primase". Journal of
`Biological Chemistry. 267(2): 848-854.
`Hanshaw et al. (2004) "An Indicator displacement system for fluo(cid:173)
`conditions"
`rescent detection of phosphate oxyanions under
`Tetrahedron Letters, vol. 45, pp. 8721-8724.
`Bai et al. (2003) "Photocleavage of a 2-nitrobenzyl linker bridging a
`fluorophoretothe 5' endofDNA,"PNAS, vol. 11, No. 2,pp. 409-413.
`Nielsen et al. (2004) "Multiplexed sandwich assays in microarray
`format," Journal of Immunological Methods, vol. 290, pp. 107-120.
`Zhang et al. (2002) "Synthesis of Releasable Electrophore Tags for
`Applications in Mass Spectrometry," Bioconjugate Chem, vol. 13,
`pp. 1002-1012.
`Katherine J. Gibson and Stephen J. Benkovic (1987) "Synthesis and
`application of dervatizable oligonucleotides," Nucleic Acids
`Research, vol. 15, No. 16, pp. 6455-6467.
`Tatyana S. Godovikova et al. (1999) "5-[3-(E)-(4-Azido-2, 3, 5,
`6-tetrafluorobenzamido) propenyl-l ]-2' ... Reaction," Bioconjugate
`Chem., vol. 10, pp. 529-537.
`Amy L. Kimzey and William S. Dynan (1998) "Specific Regions
`of ... Photocross-linking," The Journal of Biological Chemistry, vol.
`273, No. 22, pp. 13768-13775.
`Huber et al., Analytica Chimica Acta, 393:213 (1999).
`Pastinen ,Genomic Res., 7:606 (1997).
`Ronaghi, BioTechniques, 25:876 (1998).
`Weiss, Science, 283:1676 (1999).
`Finzi, Science, 267:378 (1995).
`Hu, BBRC, 254:466 (1999).
`Caetono-Anolies, Biotechnology, 12:619 (1994).
`Extended European Search Report issued Jul. 18, 2007 in connection
`with European Patent Application No. 07004522.4.
`International Search Report issued Oct. 29, 2007 in connection with
`PCT International Application No. PCT/US 07/13559.
`Notification of Transmittal oflnternational Search Report and Writ(cid:173)
`ten Opinion, issued Nov. 23, 2007.
`Notification of Transmittal oflnternational Search Report and Writ(cid:173)
`ten Opinion, issued Sep. 9, 2008 in connection with International
`Application No. PCT/US06/24157.
`Notification of Transmittal oflnternational Search Report and Writ(cid:173)
`ten Opinion, issued Feb. 6, 2008 in connection with International
`Application No. PCT/US06/42739.
`Notification Concerning Transmittal of International Preliminary
`Report on Patentability ... issued May 15, 2008 in connection with
`PCT/US2006/042698.
`Notification of Transmittal of the International Search Report and
`Written Opinion, issued May 22, 2008 in connection with Interna(cid:173)
`tional Application No. PCT/US06/45180.
`Notification of Transmittal of the international Search Report and
`Written Opinion, issued Aug. 16, 2008 in connection with Interna(cid:173)
`tional Application No. PCT/US07 /24646.
`Official Action issued May 21, 2007 in connection with European
`Patent Application No. 01968905.8.
`Official Action issued Mar. 31, 2006 in connection with European
`Patent Application No. 01968905.8.
`Official Action issued Mar. 3, 2007 in connection with European
`Patent Application No. 07004522.4.
`Official Action issued Mar. 14, 2008 in connection with European
`Patent Application No. 07004522.4.
`Communication Pursuant to Article 94(3) EPC issued Apr. 30, 2009
`in connection with counterpart European Patent Application No.
`07004522.4.
`Mathews, Christopher K. and Van Holde, K.E. (1985) "Chemical
`Synthesis ofOligonucleotides," Biochemistry, 2nd Edition, pp. 127-
`128.
`Office Action issued Oct. 25, 2002 in connection with U.S. Appl. No.
`09/972,364.
`
`Page 5
`
`

`

`US 8,088,575 B2
`Page 6
`
`Office Action issued Mar. 14, 2003 in connection with U.S. Appl. No.
`09/972,364.
`Office Action issued Aug. 10, 2007 in connection with U.S. Appl. No.
`11/119,231.
`Office Action issued Sep. 21, 2007 in connection with U.S. Appl. No.
`10/380,256.
`Office Action issued Nov. 14, 2007 in connection with U.S. Appl. No.
`10/735,081.
`Office Action issued Sep. 3, 2008 in connection with U.S. Appl. No.
`11/894,808.
`Office-Action issued Jun. 24, 2008 in connection with U.S. Appl. No.
`11/894,690.
`Office Action issued Jul. 8, 2008 in connection with U.S. Appl. No.
`10/591,520.
`Restriction Requirement issued in connection with U.S. Appl. No.
`10/521,206.
`Notice of Allowance issued Sep. 6, 2007 in connection with U.S.
`Appl. No. 10/702,203.
`Jun. 5, 2009 Office Action issued in connection with U.S. Appl. No.
`11/894,690.
`Notice of Allowance issued Apr. 2, 2010 in connection with U.S.
`Appl. No. 11/810,509.
`U.S. Appl. No. 09/658,077, filed Sep. 11, 2000, Ju et al.
`U.S. Appl. No. 09/684,670, filed Oct. 6, 2000, Ju et al.
`U.S. Appl. No. 09/823,181, filed Mar. 30, 2001, Ju et al.
`U.S. Appl. No. 09/972,364, filed Oct. 5, 2001, Ju et al.
`U.S. Appl. No. 10/194,882, filed Jul. 12, 2002, Ju et al.
`U.S. Appl. No. 10/380,256, filed Mar. 30, 2001, Ju et al.
`U.S. Appl. No. 10/591,520, filed Sep. 1, 2006, Ju et al.
`U.S. Appl. No. 11/894,690, filed Aug. 20, 2007, Ju et al.
`U.S. Appl. No. 11/894,808, filed Aug. 20, 2007, Ju et al.
`U.S. Appl. No. 11/922,385, filed Dec. 14, 2007,