'The fft·D.stees c)f Colurnbi?1 lJni-r.rersit,/ ir1 t.he (~itv
`.Ne,Jv York.
`Clf:
`
`JingyuE, ,Tu et al,
`
`1.5/380; 3.1.~~-
`
`EXt=trniner; Layla 11. Berry
`
`Art Unit: 1.673
`
`30 Rockefeller Plaza
`2ou, Floor
`r,Jt::w York: Ney,r ':{.:Jrk 10112
`
`BY EFS
`Com.tt1issioner t:o.r,- Pa t:ents
`Alexandria, VA 22313~1450
`
`1,
`
`a:::Y,
`
`I
`the first named
`iippL::Lcation,
`
`:,,n~.rentcr on the above-ident.:L:f:L,c:d patent
`
`2..
`
`I
`
`a.n1 a Prcfesst)r o:f Cl::.ernical Engineeri:t1~4 and Phar-rnacol<.1gy and
`for Genome Technology
`the Center
`the
`Bioroolecular Ecgineering at Columbia University in the City of
`
`I)iJ:~ector cf
`
`and
`
`i.dent if 1-ed pa.te.nt application and has granted a license
`
`c,f
`
`r:i qht.s
`
`i:o
`
`th~~
`
`abcve--
`
`a.t Columbi.E, has
`
`rn.echocl:s for L!Nl-\
`
`.<:JequencJ n(,1 ..
`
`P.:ci.or to 1999,
`
`wit:hi.n the human genome.
`
`Applk;ant· The Trws1e<:>S of Go!umbia
`Unl~rs,ty in 1he City of New York
`U.S. Seria: No'. ':6!"150.185
`f-'i!e,j; October Z, :Wi8
`E11:MMt 1
`
`Page 1
`
`Illumina Ex. 1133
`IPR Petition - USP 10,435,742
`
`

`

`Applicant:
`
`'the Tr.tist.ees of Columbia. Uni,.rersity iti the City" of Ne\"'
`YoX}(
`15/3;)0,311
`Serial No.
`December 15, 2016
`F:ded
`Page 2 of 8 of Declaration Under 37 C~ .. F'-..l<. .. §1" 132
`
`6. A copy of my cu:cciculs1m vitae is attached he:retc as Exhibit A.
`l am a n.arneci. inventor on. 39 issut:'-d U., s ..
`patents an-d an a':.Jt.b.or on 9-6 scier1tific [Y~lblications.,.
`
`l=s.s
`
`ir1(i:(cated-
`
`tJ~1e:::. .. ein,
`
`•
`
`Based on my e~tensive experience and expertise in the :research
`
`and development of DNA
`
`seq1.H,mcin9 and related technolo9:i.es,
`
`:Lnc.1.udinq the ciesign an 1j S}lntbesis o:f lJ.'U:cleotide Q_nalog11es 2u1d
`
`the p:ceparation ar-,d u:::e of Jab<:, led nucJ.eot.ide a ,~a_I.,::,,:,;i:1..ff,:3,
`
`I
`
`,can
`
`very well familiar with the level of education, knowledge and
`expeT~ 0 rce of persons working in these areas.
`
`8,
`
`Ba:sE,d Dn
`
`l;~qa.L advice concerning the rneaning 0£ the phras€
`~person of ordinary skill
`
`a
`
`t:h).nk
`
`l am
`
`1p,.•el:t
`
`tJn;:tJified to co111n1ent
`
`rJ:n
`
`the apf•ro-r1r'tate clef:inifion of a.
`
`field from the perspective of a POSA as of October 6, 2000. In
`
`a
`
`related discipline and at
`
`.Least
`
`two year~ postdoctoral
`
`~v~arl()US
`
`i..s::;u-:::23
`
`ra:i;-secf
`
`l:.,;/
`
`the ExarninE:r with
`
`:respec::t
`
`t~)
`
`t.he
`
`:;;.i.ngJ.e
`
`cL::im
`
`a_pplicat:Lc,n"
`
`.r. Indef.in:lte.n'i'tss
`
`2n.
`
`the
`
`patent:
`
`of
`
`.i.n
`
`context vf
`
`the
`
`Page 2
`
`

`

`Applicant
`
`Tt·v2 Trustees of Cvl-urr:b.i..:~
`York
`15,/380,. 311
`December 15, 2016
`Filed
`Page 3 of 8 of Declaration Under 37 C.F.R. §1_132
`
`lJnivE;rs:i ty ir1
`
`t::t1e c;ity cJf
`
`l.Je1.~
`
`specif i cat.:i. on
`
`pro\tidt:·
`
`a
`
`standard
`
`for
`
`assess1.n9
`
`paragraphs 6-8 of the published version of the application and
`the application .i_ncl_ud:inq
`thE, brief' descri
`
`F'i_q. 1 of
`
`of
`Fig. _ in paragraph 35, would readily have understood that the
`iridicates thdt the stanciard for as~essing v<hetf1er
`
`a,f:•p:Lication
`
`tc; tit into the a:e~ti~;e SJ. te of the DNA polyrc~erase
`.
`'
`app.c..1.cation.
`
`Fiq. 1_ OJ:
`
`t:he patent
`
`_,,
`
`sho~rn
`
`ir1
`
`and referred to in p,,,ra~p:aph 6 ot the p,1bLLsJ·,ed version of
`
`this Patent
`
`A
`
`copy o:f Pelletier et a]
`
`al
`
`1{)1'
`
`p-aqe
`
`1903}
`
`ct•s~1rce~ bet~een the ~uya~ of the nucleotide analogue and the
`
`page 1891 of Pelletier et al.I
`
`With
`in,forn1at ic}n
`
`:i.nforma.tion
`
`the p,:1tent
`
`in
`
`and
`
`t:he
`
`soft.Y.1are
`
`available in October 2000, such as Chem3D Fro, the POSA could
`the space availa~le around
`a nucleotide analogue
`
`the 3'
`
`in. the
`
`have readily calculated
`
`pc•sition of a
`
`,:Jeoxyrj_:t;ose
`
`.:_)t
`
`act ve ~;,ite c)f the polyrnera::;E: ,.
`
`Page 3
`
`

`

`AppJ . .:i.cant
`
`The Trustees of Columbia University in the City of New
`:tork
`Serial No .. : 15/380.- 311
`F,iled
`[)e(:".t~n1J::-er 15,. 2016
`Page 4 of 8 of Declaration Under 51 C.F.R. §J.JJ2
`
`in
`
`the
`
`t:he
`
`ava:i lab:l.'""
`
`z;pace
`
`is
`
`context: o:f'
`
`th•,: claimed nucleotide analogue, aD.se5sed by the
`
`sta.rtd.arc.1 p:rovic{ed
`
`.1.n
`
`t.h~e
`
`p:;:~t:ent: appli.cati{)rt
`
`rr:.ea11t
`
`a
`
`3' --Ct
`
`capping group with a diameter less than 3.7A.
`
`16. Osinq
`
`th.is starn:iard
`
`the POS.1', could have readily d,~te:cmined
`
`that
`
`two examples
`
`1..:1.sted in the
`
`ap;;;l icat:i on, Allyl and 1>1et.h•:Jxy:rn<:;thyJ t
`
`b.aci diarneters: cf 3 ~
`
`attached Analysis, Exhibit C)
`
`and
`
`therefore were
`
`17 .. Using
`
`th-i.<:
`
`::,tandard,
`
`the
`
`POSA
`
`could also
`
`re;;:.d:i.ly
`
`y, :s:ma lJ_ •·· ,.
`
`Tbu.:.:;,
`
`.F-'()SA
`
`wcruJ_d
`
`Met:hylt:hiomethyl >'ind A2.idomet:'1yl, with dif,meters of 2. 4A and
`z .. 11,._r
`cLi.arr.E:t<ar:
`
`r8spective1.y{
`
`\.,•.zE:1~c; "'sn1all ....
`
`~t,rl1il~ 2---!-Jitroben:ZJ/l
`
`tvitl1 a
`
`{>f
`
`:)j! 1r1as not. sr..aI1
`
`(sf~~==
`
`,atLached .A.na1y,t:Lis;- Ext1Lbit:
`
`C).
`
`it could
`·T'he rt.~ f c) re:
`
`indef:ini.te.
`
`fj_ t
`
`tntf,)
`
`the active
`
`sj_ te of
`
`th-e
`
`,;:,f
`
`\40t.lld not
`
`have
`
`been
`
`B. Definition of R is cLear
`
`the ~3cr11ct.u:ce sh<)wn
`
`j r: the J=:- 1_::r:cdi.:n-q
`
`,::~]a:int >::!fld tb8 -definit:icJn -oE
`
`Page 4
`
`

`

`A:ppl _:_c;a n.t
`
`The Tru;oe;tees of Columbia Unive,r~;i ty Ln the C'.:i ty of New
`\~o:ck
`15/380,~311
`December 15, 2016
`Filed
`5 of 8 of Declaratior: IJr1de:r 37 C~E- .. R., §1.132
`Paff€!
`
`R in tb<e claim ,<.Jould have been able to readily know whether
`
`within
`
`the scope at
`
`the c~alm_
`
`In
`
`this regard, prior art
`
`references as of October 2000, such as Tsien
`
`(WO 91/06673, Hay
`
`16, 1991)
`
`(WO 00/5380.5,
`
`2000),
`
`of R in the context of the patent application as a whole.
`
`~- The scop~ of Y
`
`20. Y i9 defined as a chemically cleavable, chemical linker and as
`
`shown
`
`in
`
`the structure shown
`
`in
`
`the pending claim,
`
`attached by covalent b~~As at one end
`
`to
`
`the base of
`
`ct
`
`_r1uclec1tide analog1.1e
`
`a
`
`tb.e
`
`end to a detectable fluorescen~
`
`A POSA would h2ve been
`famili,;1:r w_i tb rn..:1rty su.ch che111ical lir1kers f_rorn. the fr~ior art. ELS
`
`cf '1
`
`.:.n the c:ontext: of the pending claim as
`
`s. whole
`
`D. Other ~un~~~n~a' characteristics
`
`of
`
`patent
`
`applicat.i.on,
`
`a
`
`Fc .. :31-'-..
`
`VJ-()Uld
`
`have
`
`rE,;:,dl.Jy
`
`·1..1nde.i:-:3t ood
`
`c}!-r:~racterist ics
`
`rea()
`
`the
`
`pat,.:::;nt
`
`the
`
`encompassed by
`
`the
`
`claimed nucleotide
`
`Page 5
`
`

`

`Apr,,licant
`
`Tr;e 'T'cusu~es o:t Columbi-,i fJniversity in the City of New
`_,.fork
`15i380r3:l.l
`r:ecern})e r
`2 0 1 6
`I 5 r
`Fil i::i-ct
`Page 6 of 8 of Declaration Under 37 C.F.R. §1.132
`
`:r:r. Wr:i tten n~~scri.pti.on
`
`22., Contrary
`
`to
`
`a~sertion
`
`of:
`
`t:t1e
`
`t0,1ention
`
`for at · le-2tst
`
`the
`
`following
`
`reasnrs·
`
`standard of "small" alc,nq with
`
`the other
`
`.structural and
`
`of such groups were provided.
`
`cornplet€.,
`
`.-- There i:3
`
`.J. i.teral
`
`::,uppoxt 1.n the application for the clain,
`
`in the rejection £or obviousness-type double patenting.
`
`2.3.-
`
`FJa.s;::Ci en tf1e application, in>.~111.:ii.nq the dravJi:r~gs <;t:1(:l r::xamptles,
`
`a
`
`P{)SA woul.d
`
`:i znn1ediatel:i
`
`en-,Tisioned
`
`the
`
`encompassed by
`
`t.he
`
`"LrUGLHJ'.H
`
`recited in the claim, most of which is fixed and with only a
`
`feb·•l
`
`,,a:ciables Yihicl1 a.re we.Ll deti.nt:::ct arid. n.{)t
`
`i.nde-1:i:n:i.tZ:-::,
`
`fc,r
`
`24,
`
`disc1..1ssed
`
`.Ln
`
`th~'
`
`Page 6
`
`

`

`The Trustees of Columbia Universicy 1n che City of New
`'fc_,r:k
`.Sr,,rial No.
`15/380, 311
`F.i leci
`2 0 ~i 6
`I'>ec(}'rr~ber 15 t
`Page 7 of 8 of Declaration Under 37 C.F.R. §1.132
`
`not.
`
`by
`
`the
`
`::5tar1dard
`
`in
`
`the
`
`patent
`
`appl :(cation.
`
`25. Without the insiqht ·into l~he
`
`importance of the 3' -,('.; capping·
`
`group bE~inq
`
`a
`
`reading Stemple' s
`
`hypotl:,et ica.l.
`
`October 11, 1994,. 4259-4267}
`
`t:bat: a nucleotide analo9ue witt1 a 2-N:\.t:r:obenzyl 3' -0 capp.i.nq
`
`grour:· wculci l:1E::
`
`inc():C:t;.10.rated t,y a p(cid:144)ly1-::lerase
`
`ar1ci therefore must
`
`fit Ln
`
`the active site 01
`
`Ni trobenzyJ. group for a nucleotide analogue contai;-i.ing
`
`the
`
`qroup to be incorporated by a poJyme,:ase. Th,,, subj E,ct patEmt
`s t 8U1{) 1 8 I s
`first
`for
`the
`
`t.63.ches
`
`time
`
`that
`
`analogue with a 2-Nitrobenzyl 3'-0 capping group would be
`
`incorporated by a polymerase was
`
`incorrect oecause
`
`the
`
`Nitrobenzyl gro·c,p
`
`,.::, not "::,mall". Subsequen.tly Metzker,
`
`the
`
`\.:ra_,s not,
`
`:i.n
`
`fact~
`
`a
`
`resGl t was that
`
`t~he corc:pourid was
`
`inacti 1..1e
`
`in DNA r)oly1nerase
`
`Page 7
`
`

`

`l',.ppl i.ca.nt:.
`
`The Trustees of Columbia University in the City cf New
`York
`Serial No.: 15/380,311
`D,rzc~.n1b~x· lS; 2C16
`:?i.J.e{:::._
`Paq•3 8 ot.· 8 of Deola.tat.1.on Undex 37 C.F.R. §1.132
`
`it was:
`
`1-.. equir-e-d
`
`to. use a nucleor:ide anaJ.o.g-ue wit.tr ~ "''}srna11·•r
`
`~he sole pendin9 cla~m.
`
`and
`
`that
`
`Page 8
`
`

`

`Jingyue Ju" PhJ).
`Samuel Ruben-Pet---cr G, Viele Profo":ssor ofF.ngineering
`.Profossor of Chemical Engineering and Pharmacology
`Director, Center frff (fonome ·rechnology and Bfornokcu1ar Engineering
`Columbia University, Room 806, Nmilv,:vest Corner Building
`550 \Vest 120th Street, New York, NY 10027
`Phone: (212) 851-9191; Fax: (212) 851-9330
`Email: dj222(2ycoiurnbia.edu
`
`BIOGRAPHICAL SKETCH
`NAME
`POS!TlON T!TLE
`P:nlfosMH' of Ch~mkal Engineering and Phanna;;'ofogy~ D.frector, Center
`Singyue Ju
`for Genome Technology and Binmoleeufar Enginee:r:iug, Cohu:nhia
`lfoiversity
`
`EDUCA T!ONiTRA.lNlNG
`
`JNST!TUHON AND LOCATlON
`lJnivers1ty nfCa1ifomia at Berkeley
`University of Southern C.alifrirnia
`Institute of Chemica1 Physics, Chinese
`Academv of Sciences
`Irn,er Mongolia University, P. R Chjna
`
`Postdoctoral
`Ph.D.
`lVLS,
`
`YEAR(:,)
`1994-95
`1994
`1988
`
`FlELl) OF STUDY
`Genomics Research
`Bioorganic (11enristry
`Organic Cfo::nifatry
`
`RS
`
`1985
`
`Cl1enustry
`
`2005-Present
`
`199<"<.rf·.,n"i
`r Y ~" _ ~
`
`_
`
`ntOI<'ESSIONAL .POSITIONS
`2011- P.rnsent Sanmet Ruben-Peter G Vick Profess,:ir of Engineering, Cnfombia University
`2010· Prescr,t Pn::,fossor of Chemical .Engineering and Pharmacology, Columbia University
`:Director, 0::11ter for Genome Technology ,md Birariokcnlat Engineering, Coln.tnbia
`20{)3.,Prcsent
`UnJvernitv
`Pn;fe..sso/ of Chemical Engineering ;:;,nd Head af DN/\ Sequencing H.nd Chemical
`Biology, Columbia (renome Centci·, Columbia tJniven,ity
`~ n· ;-,;··c.
`' YI
`-~
`"
`.
`P
`.
`' E
`.
`'
`r ,.,1
`•
`.
`•..
`i'
`f·).S~Oc?ate _ ... -~rt? 'CSS{}r 0~ L,"'1~r.r:~:c31 ~,11gt!1eexn1~- ana !. ~-eau~ ~?l
`~ L" ::,equenc.1:.tg and
`Che:m,eal Bmfo1:,.,y, Colun1Dta uen{nne Center, <. .. \:dumbrn l.!mversrty
`Senior Scientist & Diu,ctGr, Chemigtry & Assay Develoµrn.,;:nt Incyt{, Cknomics, Tnc.
`
`1995~1999
`
`AWARDS
`Samuea Ruben-Pet;::-s G. Viele Prnfossor of Engineering, 2011
`Outstanding Chinese Scholar Achieven1ent />,_v.:ard, Cn1urnbia University Chinese Students and
`Sdwlurn /».;;;so{:i;1tion, 2004
`Visitfog Pn:•.fessor_ of B,~:ij~ng Capital Ur~ivernil y of ~fedi~}iJ_ Scienc.e.s, 2004
`Packard Fe,lowslnp m Science and Engmeenng, 20ul-2v,)<)
`Invited />,.ttendee, National .Ac<1,:krny of EngLneering 8th Annual l•'nmtiers
`;,~y1n_{N'Jsiurn;, f">e}"?ternber'" 2(H)2,
`DOB Human Genome Distinguished Postdoctoral fellowship, I 994--1995
`
`,f.i;ngpu,enng
`
`.,.
`.,.
`
`PROFESSJONAL ACTIVITIES
`0
`Ses~:i()n (~h.air~ i\lext C}eru.?t"<Jtion .. )e~-:ruenciJ1g (:c.qr/irt}Flce: July 7 ~ 8:, 20} i ~ San _f:ranciscl.L
`""' Org,mi1.er and Chair, 2008 Inknrntion,ll Conforence on Genomics, Hong Kcng, China, ll/2--1
`2008.
`,,. Organizer and Clw:ir, 2007 1ntern=itiorrn1 Co.nferencf o.n (;enornics, Hong Kong, Chin.a, 10130-
`11/2, 2007.
`
`Applic,~n,: The Truste,:;s of Co!urnbi.;i
`Uni,;ers,ty ifi the Clty of New York
`U.S. S0rial No: 15!3S0,3·,·1
`Filed: ;)eu~rr.b.e,· ·15. 20i6
`E:;:hih!t A
`
`Page 9
`
`

`

`"' NIH Review Panel (Genom!cs Computational Biology cmd Tr}dmol-ogy Study ,'-,yedion) 2005, 2006
`* Session Chair, "Syniposiura on New l)NA Sequencing Technologies'', Intemationa1 Conferei:1;::c 011
`Genornics, J-fa .. ugzhou, China, Octobe.r 23 ... 24, 2006.
`* Organizer a:nd Chair, "New Technologie,,; & Genorne Sequencing" BfoArmys-2004-New York
`Conference, July 26-27, 2004.
`* Organizer and Chair, "'New Technology and ToxicoCi-enomz'cs" BioArrays-2003-New York
`Conference, October 1-2, 2003 .
`., Organi:rer and Chair, Symposium on Genomics and Che:mical Biology, Post l5'i, JnternatwnaJ
`Conference on Phosphorn& Chemistry, Beijing, China, August 6-8, 2001.
`* Chair, DNA Sequencing Technology Session, Human Genome Meeting, .Human Gem:itne
`Organization {HUGO), l 997.
`s- NIH RJ)Vlevl f>anel {Genetic anri (Jeno,nic A}?}Jroaches
`Dysf'unction) 2004
`$- NIH Rev,ew Panel (Biophysical and Chemical Sciences) SBIPJSTIR 1.997--2001
`~ }~SF· Rev:ie~ .. v Panei (Ifiocl1err1ic1.7l .Engineerin.? aru.l I1iotechnot1:;gy·)- 2{l0 l
`"' DOE Hum;rn Genome Program Review Panel (Advanced DNA Sequencing Technology) 1998
`l-..,roceetfir11:-r;s t?/. the J-.lationctl .Act1deni.J1 o.f· ,.S'ciences. !Va.tu.re 1}-faterials;,
`* Rc:viewcr [Qr the .T{._!urnaJ
`1.\Iucleic /fcitf·~; l?.ese[tr;_;h_ .. Ancu~-ptic;;.il C'hemistr,y. J<_.4.(-;,')~ {)rgJ1.nic !~t·tts.rs✓ JJi;__JC;.}njugtife t~Jientistly
`ancl 13iDlt~chrtiques.
`
`/'·,l:;:rvous ;)))stern. F1-lnction
`
`t.i;:u:l
`
`f(J
`
`lSSUlID US PATF;NTS
`lJnit.ed States Patent 9,624,539 (2017) J, JtJ, J, Wu, Z. Li. "'DN~-1. Sequ.encing by :i~yrdhesi,- U,ing
`1.
`b?.l:a-n.arz and Infi"1.rrr:::c:l SrJectrosconv L}etec1."lon5
`2. United States, . .Patcnt 9,528,J 51 (2016} J, Ju, D.J-L Kitn, L Bi, Q. Meng, X. Li. '"Four-color DN,i
`
`'~~
`
`Se~u-t~u;3~g-_b!~~}7fl~~-u:;:~· ~~~}~,t~sf ~J~--r ~::,lea:~ibie ~luor,,7~cen: Nitd~wtjdc~ i~~v,:r~~;t~---1~_::r_.~i,~~f~a:~~::'~,. -,·, '•"• ": l .
`
`'t.
`
`3.
`
`5,
`
`8.
`
`9.
`
`lJmted ~tat.es 'ateI.tt Y,L;,, ,04s, (LO l OJ J .. Jt,, L Bt, D,d, Kun, Q, N ... cni-;, cnt.11-LL-c:,.,y Llc,LHU,./c. .) ..
`0--,4llyl--diVTP-All_yl-Fluoropl,YH'e Fluorescent Nitcleotid"' Analogues and }?elated lvfathods°'.
`4. United States P,tteni 9,255,292 (2016) J. Ju, (\ Meng, D . .fL Kim, L. Bt, X. Bai0 1°'t Turro.
`~':Ua·ithesis
`4½'.:·1ur•-C::?lt>r 3~:*()-all}1i A-:l<)tl{lied }-Jht;_.:tocle~rv.able Flu<Jre:)·ct::J~~t lViicleotidds i:t.nd .l?e!ate1.,.-/
`1.¼6tho;_f.s 1
`United States Patent 9,250,169 (2016) J. Ju, DW. Landry, Q. Un, T, Nguyen, R Pei, C, Oiu,
`Jvf. N~ Stoj.aJ1trvic ~;{!:/elective t:.1i.JJ?turt· <.J.rt::.i .Release ;_~f ·Ana~vtes'"'~
`l.foitcd States Patent 9,175,342 (2015) J, Ju, R Cao, Z. Li, Q. Meng, J, Guo, S, Zhang "S)mthesis
`a;l· (:leavi1ble JZ'luorescent 1Vucleotides as i?.e1Nirsible 1£:rn1inators ,.lhr 1}1V~4 J .. equencing b_.v
`:sy~rtthesis'".
`United State,s .Patent 9,169,510 (2015) J. Ju, J, W,J, DJ-t Kirn "Pyrosequencing Jvfethods and
`]?elate{-/ (:'orn.,J)Oszfu)ri::.,·',,,,,
`lhited States f'atent 9) 33,5 i l (2015} J. J11, Z, Li, LR. Fdwanis and ·y_ Itagak:i ''lvfassive Parath-1
`1\/fetho1..l_(i1r .l.)ec:orliF1g l)hlti ancl J?}tlA~·,.
`lfatl:ed States J-'ah~nt 9,115,163 (2015) .L Ju, D.H. Kirn, J. Guo, Q. Meng, Z. Li, IL Cao ''DNA
`ivt'th ?v10J1-_fluorescGnt ]'•l2.1r..:ie[Jtide
`:r·er1ninat:.)rs ar1d C{ec.1:vable Label
`.Se{yu-enclllf:;
`i(eversil:dr:.:
`lv{oc.i{fied !V~;,,cle(.>litle: Terrrii·naiot-~s'~.
`10~ lJnited States 1\itent 8"'889~3-48 (2014) J. Ju "~!Jl.f,..J /ieqiu.:ncing· iJ.Y 1'.fanl~[Jore lJsirtg 1Vi<-.)<l~fied
`
`11. United States Patent 8,796,432 (201,;) J, Ju,~- Bi, D.H. Kirn, Q, Meng "'Chemfcal{y Cleavc16le 3'(cid:173)
`()-.Ail.~vl-df\TJ]~;~Alfyi-•.F"'iuor(~l7hore Ji'lu.orescent 1\i):tcleoltfie .?lt;t:lot,_,:ue,7- and .Related 1\.fr:.::·thr>cis~';.
`12. -United Saak:s Patent 8,298,792 (2012) J. Ju, DJ·L Kim, L Bi, Q. l\.fong and X. Li ''Fo1.w-Color
`D_l\Z:<1 ,5··eq1.;,etc(:ir1g .B:y 1.\~vnthesi:S llsi.r1.g (.~h?ai,;r:1.hle f?luoresls:ent }\'ucleottr.ie l?.eve}·sible 1·er,11inr.ltorin.
`LL Unit~xl State;:-.; Patent 8,088,575 (2012) J_ Ju, z. Li, J.R. Edward::: and Y lfagaki "Massive Paro.lld
`A4ethat..l.for~ L}e(:or..1it?:f; 1)}\fA r.1:,,1./J ]?_A/..-1,~.
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`14. United States Pate:nt 7,982,029 (2011) J. Ju, Q. Meng, D.H. Knn, .L Hi, X. Bai and .i'U. Turro
`..:..;::~yntJ-u.1sis t?/'J,P-r.}u.r (;tJ-lor 3'()..al(-r/, lvfOclffied l-"}hott:K:let.ivable fat'uore._s·cent JVucleoticles aru:l Reh.:tted
`1l.ietfuJLfs''.
`15. United St:ateg Patent 7,883,869 (2011) J. Ju, D.H. Khn, L. Hi, Q. Meng and X. Li '"Ff.,,'U1·~Color
`f)l\(4 ~~;equencing ll,y ;,))ntltesis (l~ing (:,,'leavcJblr-:. Fluorr:.:st:ent }{ucleof:i<ie ll{!Versible T~:r:rninattJ: ... •:.l'y~
`16. United States Patent 7,790,869 (2010) J. Ju, Z. Li, J.R. Edwards and Y. ltagaki "Atassive Parallel
`lY!ethodfi:H· Decoding DNA and R.NA.".
`17. United St,itcs Patent 7,713,698 (2010) .L Ju, Z. U, J.R. Edwards a!1.d Y. Jtsga.ki "l!.1,tssive Parallel
`lvfethod fl,r Decoding DNA and RNA".
`l.3. United States Patent 7,635,578 (2009) L Ju, Z, Li, J.R Edwards and Y. Hagaki "Massive Parallel
`.A1eth.od jOr .1.'0ecoa1i.nJ:?' D.l-lA and R1\~4.~'.
`United States Patent 7,622,279 {2009) J. Ju, "l'hotocleavable Ji1uorescent Nucleotides
`>--'~/equencirif: on {~.'li(o (~~onstruct.ea' by f/-ite-!lpectlic (_~·ouJJifn~g C1herr:istr;l~.
`United Statca Patent 7,345,159 (2008) J. Ju. 'L Li, fR. Ed'vva:rds and Y. Hagaki "Massive A-rrallel
`lt4t:~tho<i,//Jr Decodtrtf; D1.\S4. catd J-.?.J"X.J/ff'.
`United States Patent 7,074,597 (2006) J Ju "A.fuitiplex Geno~n)ing Usirtg Solid Pha.::,e Ca1c"iw·able
`l)ide1~J,'"{.,Vn.U:l.Jt·olides and .lt-:t(.e,; .. f ,.).fJe-ctrf)lJ'!e(t·y'~_.
`Unl!ed States Paten! 7,015,000 (2006) R,.A, Mathies, .A.N. Glazer and .t Ju "Probes La.heledwith
`Energy J""t,,.r1ns~fi~r- {::ou1:let.l .!.7::y!?:S~'"
`United States Patent 6,664,079 (2003) J. Ju, Z. Li, JJ:Z, Edwards and ~r'. ltagaki «J,1assivc Parallel
`A-fethr,,idjOr- i)ecotli.n.g· T)l-.J>i a.11cl Rj\lA':;~
`Unit{~d States Patent 6,627,748 {2D03) J. Ju, Z. Li, A. Torig and J. Russo "Combinatorial
`Pf-u,._?rescence !~netff:;J,·' 7'ra.n>ay/i:r 1-.ags aru.J. tl-u"!ir ./1l~t1lications.fhr 1\fulti11lex G.ertetic ... -4nG.~lyses~¾.
`United States Patent 6.,544,744 {2003) R.A, ]\,fatbieg, A .. N. Glazer and J Ju "P;,y;bes Labeled witiz
`Energv 'Tran.sle1,,. r:.:our;le&-l Dl/e .. "i'';,,
`2.6. United Statei Pa.t~nt '6,177,247 (2001) RA. Mathies, A.N. Glazer and J. Ju ''Detection lv.fethx:Jd,;;
`[Ising· }.0 robe.s l~t--:1:.beled with E:nt?1[F T··ransj'er (~()1.ple<l LJyesJOr L.l1'v:>-1 /?raiJrne.nt Analysi:s'~-:~
`27. United States Patent 6,046,005 (2000) J. Ju, K, Korm,d. "1Vudeia Acid Sequencing 1vith Solid
`f>l1£?.Se C':a_r>turable r~er11u)ia.tors C:1ornprlJir~~g (1 (,Jea1/r-1ble L.inking Gro-upri.
`2.8. l)nited States Patent 6,150,107 !'.WOO) A.N. Glazer, RA. Mathies, S-C. Hung, and J. fo "Afethods
`<-!l" 1Sequencing a11<l IJetectit:n [/~i.ng lfr:ergv Jr-raris_f'er La~bels ;vitli (.)1,Jnine l).ye:r t:ts .[Jotior
`C l,~rorn.r..JJ.?ltJ..I r e,Y !,~,
`29. United States P,-,tcnt 6,028,190 (2000) RA. Ma!J,ics, A.N, Glazer and J. Ju "I'rohes Lahd;;.·d with
`._l{nergy -~rt•attsj'er (;;_-;u:.oierl IJ;.resJ'.
`30. United States Patent 5,876,936 (l 999) J. Ju "1Vucleic Acid Sequencing with Solid Phase
`t--:aptu.rable l'ern1-inatf)rs,~.
`31~ ·lJ:nitcd. St:ait~,:; J-latt~nt 5:,952.:180 (1999) .t Ju ,;\)ets o.f-.£Yt.r:r,gy }}'al£ ... ~fer Fi:1,,.;,t1re,sce.r~~t Tags anrJ JJr,eJr
`[ls::: ir1. A1ulti-·(~on-?lX)11.e:nt ,;:~inatj·s{s ·~ 1
`.32. tfoited St;:1tes Patent 5,869,255 ( J 999) R.A. Mat11ie0, A. N. Glazer and .L Ju '''Probes Labeled VVhh
`_Ent-;-·l;~y TJ·yu1-.tfi::r- r:.ou11lct! ])~yes f:~Xem_pl(fiecl "vFilh l)lVj.1 fl"OjJJnent .11:r-1;:.;f_ysis~'.
`33. l)nited State:.~ Patent 5~804,386 {1998) J. Jti !-\S'ets 0J·-1zner,f:Y 1Yt1n0}'er 1~~lu(rrescent Tags and ~their
`{J5e in lv!t1.lti~(:~01n12onent /Jntr{psis ,~_
`34. United Stales Pafent 5)07 ,804 (1998) R.A. Mathi.e.s, .AN, Gk,zer and J. Ju "Primers Labeled
`:vith .E)u.:1-·g}· 1)"an0~lirr (-:ouplecl l)_ves_l,:.1r IJl.,l>i .s·-e .. <1uenci>"-t .... ~~'"",
`35. United States Patent 5,728,528 {l 998) R.A. 1\.fothies, A.N. (}bzcr Rnd
`tS)Jacerl1'i.nc:rg_v Tra.~r.s_f{;:r IJ_yesn.
`:l(,. Un.ited States Patent 5,853,992 {1998) /\..N. Glazer, S-C, Hung, R.A. Mathk.s, and J. Ju "C:yanine
`l)yes v,Jith !-Titth /1.bsot~r!JJon (~.,ras .. ~~ !1"ectfo,n .as l)onor c:~hrornophores in
`1Ytin.~~fer .Prbner .. <:";;,_
`.Patent 5~814-!'454 { 1998) J. Ju ".;/Jets o,~tE~·vz.;_~rgJ' 'l~rfrnsJe;.· f?fuorescent T'ags ancl ~{'~heir
`37. I}nitt:~d StJte(cid:144)
`l_/-.;e irt ;~1ulti---(~1on1rJo.1·1ent ~4:t11..1(}'Sis "~.
`38. United Stales Patent 5,654,419 0997) R..A. :Vhthics, A.N. Gfaz;e.r and J. Ju «}--;J,u.onscr:.,nt Labels
`c_:.:nd 11·tt.-:ir (/se in :3'e1;,,;1raticn-rs';,,.
`39, United Stutes l'at<.~nt 5,688,648 {1997) R.,6,. Mathies, iLN Glazt-r tind J. fa "Probes Labeled with
`fi/nergv }'r<-fft.>/'i~r (.'?f...'rM-JJl(1fi .l.?.ves~..,.
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`.PUBLJCATIONS
`.. '])esi5'n artd t~'};;:1rl1-cterization oJr c; l' .. h.1t1o_{)Ore.._.(;10UJ:..'lecl J-)0(11Jner-12se jOr 5/ingle•-.lil'olecule D}V.11
`1 --
`Sequencing by f/vnthesis on An Electrode ArT<,:y". P. B. Stianges, l\·L Palla, S. Kalachikov, .L
`Nivala, M. Dorwi:u-t, A. Trans, S. Kumar, M. Porel, };:L Chien, C. Tao, L Morozova, Z. Li, S, Shi,
`A. Aberrn, C. Arrmk!, A. Yang, A. Aguirre, KT. Harada, D. Km-enblum, J. Pollard, A. Bhat, D.
`Grernyachim,kiy, i\. Bihmo, R Chen, R. Davis, J. J Russo, C. W. l:<11He1·, S. Roever, J. Ju. G. tvi.
`Clrurch~ lJroceeding) t~-/.lhe jV;.1tit"frtal Acacletti}.l 1.?l~;5·cfences [lt~t>1. 2016~ l 13, l16-749-f~6756 ...
`"lleal-T"i'rrte ... ~ingle--lvfole:cu.le E:iec;f:ronic Dl\(4 8!?quencing· lJy /j).1nthesfs {Jsil'lg J>olym/:.:r~l-'agged
`lVucleofides on a N;.mopore Array". C. ~N FnHcr, S. Kumar, .tvL Porei, !¥L Chien, A. Bibmo, F. B.
`Sirang<cs, J\Jt Dor'v'1art, C Tan, Z. Li, W. Guo) S. Shd, D. Korenhlum, A Trans, A. Aguirre, E.
`Lin, E Harada, J. Pollard, A. Bhdt, C Cech, A. Yang, C. Arnold, I:vL Palla, J S. Hovis, R. Chen,
`J. Momztwa, S. Kaiachikov, J. J. Russo, J. Kasianowicz, R. Davjs, S. R<;;~vex, G. ]\.{. Chmch, and
`J. Ju. Pn:,ceecling~•; r,.;f the National Academy ofScieru:es U;::.-:.1. 2016, 113, 5233--5238.
`:;.r;)\..fat.hernatical ;\Joclel ,.fi:n, .. Biornob::cula✓-· Quant[f}calfor·i Usir1g Lc1rge..,__Arer2 Surj(1ce-kJ1.htJJicet-l
`R;:1.ma.n Spectrosc,-,:oy Afapping". F. Bosco, J. Yang, T. Ri.ndzcviciu.s, TS. Alstmm. M.3- Schmidt,
`Q. Lin, J. Ju, A. Bois.en. Roy;;rl Society ofChe11iistry Advance.,', 2015, 5, S:5845-85853.
`~'-l)}'i./1{ :S'equencing by !1Yr:t.h-1,;s•n·s
`l.~1~1lng~ _1'-0~,Jzicb.);,netle~vl 1-Vueleoticie .Reversible l"e.rrninat1..:~rs and
`Surfuce--Enhonced 1-:aman S'pectroscopic Detection". M. Palla, \V. Gi:io, S. Shi, Z. Li, J. \}Vu, S.
`Jockos.ch, C. {hw, LL Russo, N.l Turro and J. J,1. F:.oya! Society cf Chemistry Advances, 2014,. 4,
`49342--49346.
`~~A 1tficrq/luidic 1),e\tlcf: .,lbr j.1uit~r;l<tx ~5z}ig/e ... /Vucleotide JJ(>l;ln1c}rj:d·tis1n (_~enoty11ing5 1
`• J. ZJ:u, t~.
`Qiu, 1\1. Palla, T Nguy<.~n, J.J Russo, J Ju. Q, Lin. Royal Sociefy of Chemist.>y AdvoHces, 20l 4,
`4, 4269-4277.
`,;.~ .. d :3/tratt:g_y {£1 (;(J.f3fure aru} C:ha-racteri.ze the ,\)N1.c~r;tic Trt:t:r1.scr1f:;trxn1.e~~. S. \/·~ Jiut1iarrveettH~ f.
`Antnnov, S, Kalachikov, P. Rajasetlrnpathy, Y,R Choi, AB. Kohn, T'vL Citarella, F. Yu, K.A.
`Karl, ivL Kinet, L Ivforozova, J.J. Russo, J. Ju, L.L. 1\.:foroz, E.R. Kandel. l'roceedings
`the
`i'-laJiana! Academy ofSciences USA. 2013, 110, 7464-7469,
`~\'>ufjGCe-E~nhaJ1ce£l
`.. \)~-ec.::troscop.Y
`,,41.1t:.-1niet·(cid:173)
`lJ:2secl Qu.(1.ntii<.:uiv{_~
`_l?.<1.rn.trn
`Bi()QSSCl;)l
`(Jn
`Functionalized Nanopillar.s Using Large~A.rea Raman Afapping" . . L Yang, r-.1. PaUa, F. Bosco, fvL
`Schmidt, T. Rindzev:idus, T. Alstr01n, A. Bois,::n, J. Jn, Q. Lin .. AC';)' Nano, 2.0l3, 7. 5350-5359.
`"'.it.1e<,,·hcu-,~isrn qf . .Al-t'{e.x.ibiiitJ~ (~~ttl'Jtrtu\fO,v :..-:i:Tl? --:-1ccess qf,ffi.pttlitis c~· Virus }\;':,'_;3 }lf:lfr.:ase'\ I\-i. Palla.,
`C.P. Chen, Y Zhang, J . .ti, J. Ju, J.C. Liao. J Biumol. Strv..et, L~vn 2013, 31, 129-141.
`~\u E;(I-l::Jbel.1-.~cf 1Vuc}eolitles crna' !\/atu:;1;x>re D"'::c:teclior; J-l~sr· S't:1s1,gle lvfol~~cule. .l)lr.£4. ,S~quePu::lnJJ,: bJ.:
`Synthesis". S. Kumar, C Tao, },,1. Chien, B. Hellner, A, Balijepalh, J. Vi. F, Robertson, Z. Li, J, .J.
`Russo, J. E. Reiner, J. J. Km;ianowicz, and J, Ju. Sctent)fic Repom:. 20 i 2, 2, 684, l--8.
`<\\.fitochoru:lrtai
`... ;-;;.t,.lf'
`lt.1~11 .. Dl-l\)li'
`!:J~~JectrOr':n;tr,y L~ring-
`(.~fe:.avahle
`l-rJ/
`/;,:fas._t
`(/x7l:iot}JJi.ng
`ffinlinylated Dideo;,.-ynucleotides''. C. Qiu, S. Kun:,ar, J, Guo, J. Lu, S. Shi, S,rvt Kalachikov, J.J.
`l-htss<:;, A.B. 1'-fa1ni, f-:-:.A. Schon and J. Ju . . 4..nalyhea! Biochr:.,mistry. 2012, 427, 202-210.
`""£Jesi)Jr; <.Jn£l ~vntlresl:1" qf' c-:te,.-1.vCt~ble Rioii~t~yli .... ;.t;;:,d .i)ideo..:rJ=1-i-ucleoti,:}es J;jr l)i.\l,,!l :Sequencin:g~ b __ v
`A:UL.Dl-TOF lvlas.~ S),ectrometry". C Qh1, S, Kumar, J. Guo, L Yu, V./. Guo, S. Shi, J. J. Russo,
`J. Jue ~4;-u:tl,.,vtfcai ]J-;,(:;(Jtenii:stJ~V} 2012~ 427:- 193-201.
`"Fluorescent Hyl:m~ifzation Probes f;r lvuc!eic A_cid Detection". J. Guo, J. Jn, N.J. Turro, Anal,
`Bioana!. c·hem, 2012,, 402, 3115-3125.
`":..(_~c.t:~/2./Zn..,<; C'<)t.Y! /Sheil {)u,t.intun-: _lJot-basecl P'f?.f.~T lJitu~~r_y ()ligorrur.::·leotit.fe Prol;es jOr l)etection
`of lv'ucl~'ic Acids''. ''{_ Peng, C, Qiu, S. Jod::uscb, Atvf. Scott, Z. Li, NJ. Tu.rm, NJ, J. Ju .
`. l 1hcitf}Cherrt.~ .l->h(j/Obfr)l. Sci., 2012,. 11~ 88r-884
`{C.,Qu-(us~fitative l{,v{1l-ut-;tit:r1. t?,.f✓1ll }fe:xcuners as Exotdc :,5[)licin:f{ .,~~lernents·r,_ S, Ke,_ S. Shang=- S. l\11.
`Kahichtlwv, I. Morozovu, L. -Yn, J. J Russo, J. Ju, and L. A. Chasin. Genome Research. 201 i,
`21, i360 .. l374.
`?!Fir.;•/ (;,r.:neratiotlu ,AufrJ1rtc!leri I)l\~A ~5equetu.:ing 7~~:c}u:tologF. I3.E,
`Sh1tko, J. Kielecnn•1a, J. Ju,
`Alo! Biol. 2011, Chapter
`.AwmbeL Curr
`A.F. Gardner, C .. L
`lL:.:ndri .. ~k"on, F.JVL
`.r'nHoc.
`7:Unit7.2.
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`'°'l: ... :Mltivation ~l Ehterobacter Hornu:tt.'chei From Human Atherosderoth:.: Tissue'\ B. Rafferty, S,
`Doigikvich, S. Kalachikov, l. I\.forozova, J. Ju, S, \,Vhhtjer, R. t,,fo,,:vygrc,d, E. Kozarov,
`A1herosc!;~r Thromb. 201 l, 18, 72-81.
`"'T'ranslational Control Anaiysls b)/ Translati'onafly Active RNA Capt;..we/lvficroarr'a,-y Analysis".
`K. Kudo, Y. X.i, Y. Wang, B. Song,, E. Chu, .L Ju, J. J. Russo, and J. Ju. Nucleic Acids Research.
`2010, 38, e104.
`"'.;_..ti,i Integratet! S.vstern j1'.?r .01Y~t ),S7equen.cir1g b,.v /)J}nth1;.:tsfs Using /\Jovel 1Vucleotic.lc .llnalogue:/\ J
`Guo, L. Yo, N.J. Turro, .L Ju. Acc. C'hem. Research. '21)10. "B, 5.51-563.
`"DNA Sequencing by /-(yr:ihesis ,U:,ing Novel 1\Jucleoiide Ana!rz.'sues". L. Yu, J Guo, N }(u, Z. Li
`and J. Jo, Handbook ofJ'v!utation Detection (Eds K. l\1eksem and G. Kah!) 2(110, 319-·3 36.
`,,.~Rc.?/J.r·o.,.._frray{-i1:\ ... : A c:D-1V .. 4 ,nicroarraJJ .lltr icltrn.tij1.c,:rtion qf' f·eprr_.1tiuction~relr.it::..:ci genes· in tfte
`R,if2t1.t tig,r,.:rr .. "':·hrilnt-) J>en.aetlS rnonodon al'l::l clUJ,rti::./t{:!.r{z.al'ion, of~ ti novel .>1uciear -tJutr.,..a,iti,ze.Yxf,.,~
`,;,rmein (JVAS'l~) gene'' N. Karn0nutl1aisiri, K Sittikankea\V, R.. Preechaphol, S,
`:rperm
`Kalach1kov, T. Wongsurawat, U. Uawisetwathana, J. J. Russo, J, Ju, S. K!inbunga, K. Kirtikara.
`Comparative Biochemistn· and .Phyxio!ogy, Pllrt D4, 2009, 90--99 .
`1entrotern .. oo.-ral sha1~.o 1:vr.nle l?E(i irl:tit jn rolcrndic ez:Yile_r:••i,)/ ,n~1}JS h} lC!t}P\-rJ{Itor f'}roteitl (;r.•J1nf>le~';f:
`4 (ELP4)'\ LJ. Stn::.g, T. Ciarh:, T. Chiang, J'vL Chfon, Z. Hasku:rt, W. Li, R. Dorfman, B. Bali, E.
`Wirrel1, S. L. Kugler, D. E
`tvfanddbaum, S. M. Wolf, I'. McGoldrid:., IL Hardison, R J,
`Ncivotny, J. fa, D. A,. {Jrecnherg, J, J. Russo, D. IZ .. Pal. Eur. J Hum. Genet. 2009, 1?, 1171•·
`J18L
`[Jlv>l Seque:ncing lvith 3 ,' .. ()--;,no-tl{fied l'lucleotide Re1..1e'rs£l1le T€rn:1h·ic1.tot·J
`,~ 1~=)our..,,color
`Cfi'it~i
`Che,nfcal(v Cieavable Fluorescent .Dideoxynudeotides". J. Guo, N. Xu, Z. Li, S. Zhang, J. \-Vu.,
`D. Kim, M. S. Iv1arrna, Q. Meng, H. Cao, X. Li, S. Shi, L Yu, S. Kafa.;::hikov, J. Russo, NS
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`35 a
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`37,
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