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a a TO PTO RRS aa FR Appicaon Number 121642, 658 INFORMATION DISCLOSURE Filing Date ‘March 15, 2013 ‘STATEMENT BY APPLICANT First Named Inventor Jennifer DOUDNA et ai. (use 28 many sheets as necessary) Examiner Name | Michele K: JOIKE: ‘Arne Becket No” 0064483-00000 shen _t_of_7 U.S. PATENT DOCUMENTS: =xaminer Jecument Number- lame of Pat ‘or Applicant Fages, Columns, Lines Sime | "na Coce seed Docent _| Wee eon Pansges ors-oo20225 4-15-2016 | Fong ZHANG eta Bors-o0stise 01-26-2018 | Feng ZHANG ot a [== poiscmnsere 07-23-2015 | Feng ZHANG. p016-0232882 08-20-2015 | Feng 2HANG ota Bors.o16439 07-02-2015 | Feng ZHANG ot a pors.0247150 09-03-2018 | Feng ?HANG eta [——hors-o232089 08-20-2045 Vames DAFLMAN ofa. 2075-0050609 | 02-19-2015 \Virginijus SIKSNYS et al. pois.020026% 08-27-2018 |Viginjus SIKSNYS et a. [9,023,649 (05-05-2015 [Prashant G. MALI et al. ] pors-007 1680 03-12-2018 [Kran MUSUNURU ot | pors.0732035 08-20-2018 [Prashant G. MAL al ors.0225738 08-13-2018 [Danial F_ VOYTAS eta. Bora.o294773 10-02-2014 [Sian Johan Joze? BROUNS eral pors-onaaa 01-22-2015 [Sian Johan Joze? BROUNS e 1015-0128307_ 05-07-2015 Lakshmi SASTRY-DENT et al pois 0728808 05-07-2015 [Lakshmi SASTRV-DENT eta. ors.0126300| 05-07-2015 [Lakshmi SASTRY-DENTTef al pots.0240263 "06-27-2015 [Michael HOLMES a. _ f013.0308670 #1212013 [David FRENDEWEY eta. ois-015s174 36-11-2018 [David FRENDEWEY et a. 015-0159175 06-11:2015 [David FRENDEWEY eta. 140235033 08-21-2014 Veffey D LEE eta. bo1s.0031089| 04-28.2018 [Derek Loe LINDSTROM pore.0386867 12:04-2014 [Brian Jon PETER oto. pors-021 1086 07-30-2015 ~~ [Carsten-Pefer CARSTENS ois.0126300 05-07-2016 [Soren WARMING ete. Boia. 0349405 14-27-2014 erie. SONTHEIMER ofa. Bois.o2sz60t 08-20-2016 ~~ [Wexandra, GLUGKSMANN ofa pots-0225601 08-19-2016 [Cong CATatal 075:0250684 08-17-2018 [George M. CHURCH etal. 016.0259704 00-17-2016 [George W. CHURGH eta. 2046.0267776 09-26-2015, jae Keith JOUNG ef {~ 2015-0267205 09-24-2015 [Steven FROELICH et al. [ 1015-0291961 10-15-2015, Virginijus SIKSNYS et al. i015-0265265 10:08:2015 [Sholom PEYMAN Bois.a2ea727 40-08-2015 [in-So0 Kit ot a. Bo1s-0287965 70-15-2018 [Fang ZHANG eta. i016-0297966 10-18-2015 Feng ZHANG et al pis.0201869 10-15-2018 [Ramesh 6. NAIR ef al. Same - Owe Sonus Cone EXAMINER Taal TTararcn Considered, Whether ot elaton in conformance with MPEP. § 60S. Oraw Tine Urough elation Worn conformance ‘and not considered. Include copy of Ns form with next communication to Applicant ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKJI ‘Siti rtm PTORBIBa ad TOROS Complete Roan ‘pplication Number 197642, 659 INFORMATION DISCLOSURE Filing Date March 15, 2013, STATEMENT BY APPLICANT First Named inventor “Jennifer DOUDNA ef a (se a= many sheets as necessan) Examiner Name Michele K JOIKE. ‘Atomey Docket No. ‘0084843-00000% Sheet_2 of 7 (07010076087 03-25-2070 [Ek J. Sontheimer ot af [201170180776 (08-04-2011 [Rebecca Terns et al B11734,256 [72-06-2072 IFugiang Chen [51758624 04-30-2013 [Fugiang Chen [61761046 (02-05-2013 [Scott Knight [p1794,422 03-15-2013 [Scott Knight a] [b11735,876 12-11-2012 [Blake A. Wiedenheft [p17799,531 03-15-2013 [Blake A. Wiedenhoft [517738,355 2-17-2012 (George M. Church 7 [B1779, 169 03-13-2013 Prashant Mali [611613,373 03-20-2012 611625,420 04-17-2012 (00370186238 0-02-2003 (Alwi st ar 7201070055798 03-04-2010 Thomas R. Battersby 200670234247 70-18-2006 IMadaiah Puttaraju 983,233, (03-31-2015 (Zhang ef al. 7 989,641 (04-07-2015 [Zhang ef al t — FOREIGN PATENT DOCUMENTS Foreign Patent Document STATUS noneotranesr [|g] 8 wle Examioer| county Coe’ Menor, | Pubcon Dato oscars age PE lag) a] flomer| was’ | commcatgemes | ieans oma EVP ag |] 2] a |osser Wo H0ToTN6sT08 [05-14-2010 — | Univerly af Goole WO 20%4/053479” | 06-18-2014 [Montana State Unversiy Wo 20%1/ta6121 | 1-24-2011 | Sengamo Biosciences Inc a arn ea Ba ch NON-PATENT LITERATURE DOCUMENTS ae THluGe Tare The author (n CAPTTAL LETTERS), te af he acl (when appropiate), ile oe Ram (Boer, magazine ery ural, seal, symposium, catalog, et), date, poge(6),velumevssue numbers), publisher, ckyenclorcounly where published 1 [information Disclosure Statement for U.S. Application No, 14/104,990 filed September 4, 2016. Federal Circuit decision in Dow Chemical Co. v. Nova Chemicals Gorp. Appeal Nos. 2014-1431, [2014-1462 (Fed. Cir, August 28, 2015) (Dow v. Nova). 3 Baker, Gene Editing at CRISPR Speed, 32(4) NATURE BIOTECHNOLOGY 309-312 (April 4, 2074) INtukhopadyay, “On the Same Wavelength, ASBMBTODAY (August 2074), available at 4 _Inttp:ww.asbmb orgiasbmbtoday/201406/Features/Doudnal (printed September 14, 2016). IConnor, "Scientific split- the human genome breakthrough dividing former colleagues,” THE 5 [NOEPENOENT, Friday 25 April 20 14, avaiable Inttp:siwiww independent.co.uk/news/science/scientiic-split-the-human-genome-breakthrough- ldividing-former-colleagues-9300456 htmi(printed September 14, 2015). earner Bate Signature Considered FEXANINER: [ial veleratcn Considered, whether o7 not lation in confaimance with HLPLE-P. § 609. Dvaw ine Iiough Glation Waal conformance fad not considered, Include copy ofthis form with next communication to Applicant. ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKJ/ ‘Sate or toms PORES Bad PTOSEORS Campate i Krewe ‘Application Number 13/842,869 INFORMATION DISCLOSURE Filing Date March 15, 2013) ‘STATEMENT BY APPLICANT First Named Inventor ‘Jennifer DOUDNA ef af (use as many sheets 2s necessary) Examiner Name Michele K. JOKE ‘Atlomey Docket No. (0084443-000001| 3 of 7 NON-PATENT LITERATURE DOCUMENTS Tihige rare of he aur (a CAPITAL LETTERS), feof the ariel (when sporeprate), ite of he Wei (book magazine a ‘pura saa oyroostan caldoy et) dae page(s), vue eoun nner pobieer, ety adr county where aubised lishimasu et al., Crystal Structure of Staphylococcus aureus Cas9, 162(5) CeLL, 1113-1126 (August| 8 by. 201 §). 7 [Third Party Observations Conceming EP Application No. 13793997.1, September 4, 2015, 8 [information Disclosure Statement for U.S. Application No. 14/105,035 filed September 10, 2016. [PowerPoint slide entitled “Development and Applications of CRISPR-Caso for Genome Editing” ldated September 9, 2016. 10 PowerPoint slide entitled "Interview 9 September 2015." 15 _|Selected Claims of Applications Being Interviewed 9 September 2016. (Bhaya et al, ORISPR/Oas Systems in Bacteria and Archaea Versatile Small RNAS for Adeptive IDefense and Regulation, 45 ANNUAL REVIEW OF GENETICS 273-297 (2011). [Deveau ef al, CRISPR/Cas and Ils Role in Phage-Bacteria Interactions, 64 ANNUAL REVIEW OF IMicroiou, 475-493 (2010). 18 [Office Action issued in Application No. 14/705,719, dated September 2, 2015. 16 7 19 [Preliminary Amendment fled in Application No. 14/683,443, dated June 18, 2015. [UK intellectual Property Office (UKIPO) Examination Report for GB1420270.9 issued August 17, 12015. 21 _ {Third Party Observations fled for GB1420270.9 on July 13, 2016. 20 23. [Preliminary Amendment filed in Application No. 14/681,510, dated August 19, 2015, 24 [Exhibit 0, Interview Agenda for September 9, 2015 interview. [Ex E, Zhang/Broad Application No_14/105,031 as Doudna Provisional Application Nos. 7852, 086 and 617 falfo Teach or Suggest Claimed Invention = [Exhibit F, Zneng/Broad Appication No. 14/105,036 as Doudna Provisional Application Nos 2 lexnibit G, Zhang/Broad Application No. 14/704,551 as Doudna Provisional Application Nos. rOee a m = Dale Considered EXAMINER TVA Wierence considered, whether or not ciation & ha eanfermance wih MPEP. §608. Craw ine Waugh cation nat eanformance ‘ang not considered, Inclice py of is form with next Communication to Applicant ‘ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKJI aes PORE od TODOS Campa Rnown aon Number 137642,859 INFORMATION DISCLOSURE ng Date March 15, 2013 STATEMENT BY APPLICANT First Named Inventor Jennifer DOUDNA et ai. (ove as many sheets 28 necessary) Examiner Name Michele K JOKE ‘Attorney Docket No (0084443-000001 J Sheet 4 of 7 NON-PATENT LITERATURE DOCUMENTS cane Trude Ta Oe avo e CRPVAC ETERS), sate ATIC When sppropraa), ie eam ook, magazin marie Vural eet symm cg, sc) ele, eee) vane monastery dor eu were pub lExhibit H, Zhang/Broad Application No. 14/497,627 as Doudna Provisional Application Nos. an 286 Fall'o Teath or Suggest Claimed Invention: [Exhibitl, ZhangiBroad Application No. 14/104,990 as Doudna Provisional AppIeaton NOS. Ebi ad Te Ree Pao Tosh or Comer Chained enon Go Exhibit, Minton, How Can Biochemical Reactions Within Cells Difr From Those ia Test Tubes?, 1148 JOURNAL OF CELL SCIENCE 2863-2869 (2006). Sy EshibitK, Elis, Macromolecular Crowcing: Obvious but Underappreciated, 26, No. TO TRENDS ® BIOCHEMICAL SCIENCES 597-604 (2001). [Exhibit L, Sanders et al, Use of a Macromolecular Crowding Agent to Dissect Interactions and 32 |Betine Functions in Transcriptional Activiation by @ ONA-Tracking Protein: Bacteriophage T4 Gene [45 Protein and Late Transcription, 91 PNAS 7703-7707 (1894). a Ga Bupplementatinformaton Disclosure Statement for Application No, 74705,037 fled Seplember 4, bots. 34 [Response to Office Action for U.S. Application No. 14/704,651 filed October 2, 2016. 35 [Response to Final Rejection for U.S. Application No, 14/481,338 fled October 2, 2016. 36 [Response to Office Action for U.S. Application No, 14/705,719 fled October 2, 2016, G7 [ntermation Discosure Slatement ard Inleview Summary for US. Application No, 147104 900 fied Joctober 2, 2015 38 IHsu ef al., Development and Applications of CRISPR-Cas9 for Genome Engineering, CeuL. li57(6):1262-78 (2014) Go Hwee at, Ericiont Genome Engineering ih Eukaryotos Using Cae® From Steptecossus Inermophiius, Cet. Mot, LiFe Sci, 72(2):383-99 (2014) 49 (Karvelis et al, (RNA and tracrRNA Guide Cas9-mediated DNA Interference in Streptococcus | linrmophilus, RNA Bio.oGy, 10(5)'841-54 (2013) “a1 Danielsson ef al, Thermodyramics of Protein Destabilization in Live Cals, PNAS, 172(40) T2402: JO7 (2015) “42 [Emais from Thomas J. Kowalski to USPTO Personnel, dated October 12, 2015 (80 pages) 43 _ [Advisory Action for U.S. Patent Application No. 14/481,399, dated October 23, 2015 “a [Response to Final Office Action and interview Summary for US. Patent Appieation No, 14481,338, fled October 30, 2018 [Exhibit C5, Zhang/Broad Appicalion No, 147105,035 as A Demonstration thatthe Final Office Action lobviousness. ge ond et af, Supplementary Material: Maliplex Genome Engineering Using CRISPR Cas Systems I339 Science 619-823 (2013) Gr (oho et a, Supplementary information: Targeted genome engineering inhuman Gels with RNA- lguded endonucleases, 31(3) NATURE BIOTECH 290-232 (2013) “e[Biard et af, CISPR interference Can Prevent Neral Tranefarmaion and Virulence Acquistion during in Vivo Bacterial infection, Ceu. Host & MicROBE 12:177-86 (2012) Srariner Date Signature Considered “EXAMINER. TT H reference considered, whether ar nol aaion eh convommanea wih MPEP, § 608, Draw ine tough cation not conformance ‘2nd not consideree. Include copy of this focm wih net communication to Applicant. ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH, /MKA! [ Sct orfoom PTOI aod PTOSEI Conpiete i Known ‘Applcaon Number 191042859, INFORMATION DISCLOSURE Fring Date March 16, 2013 STATEMENT BY APPLICANT First Named Inver “Jennifer DOUDNA eta (use as many shets os nacesany) Examiner Name Wichele K, JOIKE Atiomey Docket Na ‘0084449-000008 Sheet 5 of 7 NON-PATENT LITERATURE DOCUMENTS = ia are a Ta a CAPITAL LETTER os IGEN SSSI, OST A, REA, arin esis, se 6) am, pa) arm nmr) ts ly ear ew Ge Daisenke ef al, Molecular Wommory of Prior ifections Acivates the CRISPRVGas Adaplve Bactoral limmunity System, NATURE COMMUNICATIONS 3:945 DOI:10, 1038/ncomms1937 (2012), Go Pougach ef a, Transcription, Processing, ond Function of CRISPR Cassetes in Escherichia col IMou. Microaio.. 716) 1367-70 (2010) Fr Banaszewska a1, Proprofai Convertase Subilsi”Kexin Type & A Now Target Molece Tor IGene Therapy. CELL, MOL, BIOL. LerTERs 17:226-30 (2012) Gp Koomneet ata, Aipolinoproten 8 Knockdown by AAV delvared EhRNA Lowors Pasria Cholesterl lin Mice, MOL. THeRAP, 19(4):731-40 (2011) Ge Mala a, Supplementary Matorals: RNA-gulded Ruan Genome Engineering va Ca, 390 {Science 823-826 (2013) Nomura ef al, Low-density Upoproten Receptor Gene Therapy Using Helper-Dependent 54 [Adenourus Produces Long-term Protection Against Atharasclerosis in @ Mouse Model of Familial IHypercholesterolemia, GENE THERAPY 11:1540-48 (2004) Ge [eabriel et a, An Unbiased Genome-Wie Analysis of Znc-ingor Nuclease Specialy, NATURE Biorecn, 29(9):616-24 (2011) Ge eewis eta, Tho c-nye and PyliT Oncoganas Induce Dlferent Tumor Types ih a Somatic MOUs _ |itose or Pancreatic Cancer, GENES DeveLorwent 17:3127-38 (2003) Gr Wandel ef, Vesatie and Effcient Genome Eating in Human Cells By Combing Zine Fiiger INucteases with Adeno-Associated Viel Vectors, HUMAN GENE THERAPY 23:921-29 (2012) Ga Asef a, Directed Evolution of Adeno-assooieted Virus fr Enhanced Gene Delivery and Gene frargoting in Human Pluriootent Stem Celis, Mot, THERA, 20(2'329-38 (2012) Gp sian ef a, Supporting Information. Targeting DNA Double-Srand Breaks wi TAL Effector INuctoases, Generics 186:757-51 (2070) Gols ota, Zin-fingor nuclease-modiatod geno carecion using single AAV vector vareducton and lenhancement by Food and Drug Adminisralion-approved drugs, GENE THERAPY 20:35-42 (2013) IHBDI et al, RNAFmediated knockdown of HM Co reduclase enhances gone expression from 61 physiologically regulated low-densily poprotein receptor therapeutic vectors in vivo, GENE THERAPY f9:463-407 (2012) Gy [anssen etal, House modes of KES iate carcinogenesis, BOCHWCR ET BIOPHYSICA ACTA 1756:145-154 (2005) Ge. Oelicheva et ar, CRISPRRNA maturation by tans-encoded small RNA and host factor RNase 1474 NATURE 602-609 (201) CDelicheva) with Supplemental Figures 62 posing Claims oS Patent Applcatiaa Na t4l628 209 71 [isDeveau etal, Phage Response fo CRISPR Encoded Resistance in Streptococcus themeophies, 190(4) J BxcTeRioL 1380-1400 (2008) (‘Deveau") aa Date Strate onaaree EXAMINER [nie Telaronce COnaISarad, whether oF nol ctation in conformande with M-PLEP_ § 608. Dvaw ine Trough elation Wot conformance ‘and not considered. Inlode copy ofthis orm wit next communication to Appian ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKJ! Soba tam POR and PTOTSEES Complete WKrown ‘Application Number 134842,659 INFORMATION DISCLOSURE Filing Date March 15, 2013 STATEMENT BY APPLICANT First Named inventor Jennifer DOUDNA et {se se many shee as necessary) Examiner Name Miche'e K. JOKE, ‘Attomey Docket No (0084443-000001 Sheet _6 of 7 NON-PATENT LITERATURE DOCUMENTS. Donner Thode wate he author (i CAPITAL LETTERS), oof ala (when appropiate), We of ie Rem Book magazin, — [ural eral, symposium, catalog, et), date, page(s), vlume-ssue rumber(s), publisher, ety andor cour were published. 72. |F-Molica et a, Short motif sequences determine the targets of the prokaryotic CRISPR defence Isystem, 185 MicroBioLocy 733-40 (2009) (‘Mojica") 73 MW Hwang eta, Etfcient genome editing in zebrafish using a CRISPR-Cas system, 31(3) NATURE IBioTecw. 227-229 (2013) 74. 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Sanjana et al, A Transcription Activator-Like Effector (TALE) Toolbox for Genome Engineering, 81 I7(1) Nat PRoTOC 171-192 (2012) ap ,Pauletal, Locaized Expression of Small RNA Inhibitor in Human Cells, 7 MOLECULAR THERAPY les7-247 (2003) ga _[R Keutman, Overview of Vector Design for Mammalian Gene Expression, 16 MOLECULAR IBiorecHNoLocy 151-160 (2000) IS. Hong et al, Functional Analysis of Various Promoters in Lentiviral Vectors at Different Stages of 84 _|in Vitro Differentiation of Mouse Embryonic Stem Cells, 15(8) MOLECULAR THERAPY 1630-1639 \2007) J. Crasto and J. Feng, A LINKER: a program to generate linker sequences for fusion proteins, 85 1136) Protein ENcin. 309-12 (2000) ‘Tan et al, Fusion proteins consisting of human immunodeficiency virus type 1 integrase and the 86 [designed poiydacty! zinc finger protein E2C direct integration of viral DNA into specific sites, 78(3) J ROL. 1301-13 (2004) 87 [R. Gordiey et al, Synthesis of programmable integrases, 106(13) PNAS 5053-58 (2008) 88 (C. Gersbach, Targeted plasmid integration into the human genome by an engineered zine-finger Eraminer oat Signature Consideres SEXARINER Ta Terence consldered,whelher oF Fel Salon in canfannance with MPE ‘F6GO. Draw ine Hough elation Wot conformance ‘and not considered. nude copy of ths form wih next communication to Applicant ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKA! isn roms PFO and TONERS Campiete TRown ‘Application Number 131842, 859 INFORMATION DISCLOSURE Filing Date March 15, 2013 STATEMENT BY APPLICANT First Named inventor Jennifer DOUDNA af a {use as many sheets as necessary) Examiner Name Michele K_JOIKE ‘Attorney Docket No (0084443-000001 Sheet_7 of 7 NON-PATENT LITERATURE DOCUMENTS a TreoGe aie he Bur Te CRPTTAC LETTERS), We Wis aS (wh Sapp), fh Tam ook, agar ae ia teral spe, alg ee) ete, gee) vre-anve mumae) pba andor eau wre publ Vecombinase, 36(17) Nuc, AGIOS RES, 7668-76 (2011) 9S: Hacein-Bey-Abina of al. Sustained corection of Xinked severe combined immunodeficiency by lex vivo gene therapy, 346 N, ENGi, J. MeD. 1186-93 (2002) | go (¥ Santiago et a, Targeted gone knockout in mammalian cels by using engineered zine-nger Inucleases, 105(15) PNAS 5809-14 (2008) 1 (6. Costet al, BAK and BAX deletion using zinc-finger nucleases yields apoptosis-esisiant CHO cells, 105(2) BIOTECHNOL. BIOENG. 330-40 (2010) gg OL Xu& TH. Bestor, Cytasine methylation targetted (0 pre-determined sequences, 17 NATURE ENETICS 376-378 (1587) 3. Blancafort et af, Designing transcription factor architectures for drug discovery 66(6) MOL PPrarWacoL 1361-71 (2004) ea PCR Applications Manual 3° Eaition, Roche Diagnostics GmbH 1-240 (2006) Sarit Date Signature | Michele Joikel Consideros ‘anereots EXAMINER. Till retarence considered, wale not ciation in conformance wih MPEP. § 608” Draw ine Wirough Gaon Watin conformance ‘and not considered. Incude copy o his form with nest communication to Applicant, ‘ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKJI Sa on OST oe FORTS Canaan Fopicaon Nae Tareas INFORMATION DISCLOSURE Filing Oate ‘March 15, 2013 STATEMENT BY APPLICANT —_[ Fist Naredinvenor [Jenner DOUDNA oa (ue ermary sheet a essay) Examine Name itchalek JOKE iitmey Dosket Na 20843-09007 Shoot_t_ot_ 3 U.S. PATENT DOCUMENTS ‘Examiner | Document Number Publication De Name ofPatente or Apaticant | yraaee, counts Tes ‘ao ‘one aeoorne Guest nt van Posies TB ATT (Fed 07-02-2073) [Fang ZAANG ea. Bv756 466 (Filed 07-30-2013) [Feng ZHANG et al. 7765046 (Fed 02-25-2013) Feng ZHANG ef a. 7751 a0 (Fed 03-15-2013) eng ZHANG ef a 602.474 | — (Fed 03-15-2013) Feng ZHANG eta. 706 375 (Fed 03-26-2013) Feng ZHANG ef a Bve14 263 Fed 04-20-2013) [Fong ZHANG of a SIEKIE (Fed 05-06-2018) Feng ZHANG eta. Fve2a. 120, (led 05-78-2018) Feng ZHANG eta. 51695.831 (Fed 05-17-2013) Feng ZHANG eta. Fe36.127 (Fed 05-17-2013) Feng ZHANG eta. Barina (Fed 0-73-2012) —ir-Soo KM eta 7000.509 (Fed 03-20-2013) —|ih-Soo KiMfet a Bs1637 461 Fed 06-20-2013) —[in-Soo Kilo rabee.7e2 (Fed 11-16-2018) [Dou etal FOREIGN PATENT DOCUMENTS Fanta Puen cone ame ronectrammeer (FTE T EE =| |onsnen Eamier| ny cai’ rim, | Puskasnoate | “ceteris ; 2| Fl oes ita | Gage | (KOO) Dome PLETE B/E | Ne The Broad ite, re, Massachusetts Insitute of Technology: Presidents ad] epzreassze1 _|os.o8.2018 _|Fetows of Harvard Golege NON-PATENT LITERATURE DOCUMENTS Teannar | te nae dh ao: CABAL LETTERS) le he ae hen oppapiin) Se le Ron fok mga, ie ib ympsion cng} ete poqtl wane sev ron) ahr ty sr cunt tee pares shui a al Natonal stu of Oabetes and Digesve and Kidney Diseases, National sites of HeaTh NIH) Research Grant No. 1RO1OKOB7768.01 submited by The Broad insite, Inc, published 6 October at ‘Campeau ef al_, “A versatile viral system for expression and depletion of proteins in mammalian cells," PLoS one, s(@), 6529 (2008) Fnov eta. “Gener edHiig Wit enghieered ave Tiger NICEREEE” Wat Rav. Genel, T1SIES (20T0) Sriovi la WoaTed gateway ste Tor double snRNA expression and Grex based gene [eipression* Bide Biotechnol, 11:24 2011) ang and Sander “TALENG: @ widely applicable tehndlogy Tr argeled genome eaiing? Nat Rav. Mal Ge Bor 44:49:85 (2013) [eam oa Soave Cana “EXARANER ial WToTSneeconederod, whether 6 at elaon fn eonfomance win MPEP. § 608. Daw ie inveugh Gaon Wnat i cotarmance ‘ndnot considered, Inde copy of form with next conmureatio to Applicant ALL REFERENCES CONSIDERED EXCEPT WHERE LINED THROUGH. /MKJ/ ‘EA Teo PYOSSDEG and TORBIS amelie Row ‘Appiicaion Number ¥97042,059 INFORMATION DISCLOSURE Filing Date ‘March 15, 2073 STATEMENT BY APPLICANT First Named invertor ‘Jennifer DOUDNA of al (use as many sheets as necessan) Examiner Namo Micnela K.JOIKE ‘Attomay Docket Ne ‘008¢443-000001 Shoot 2 of 3 NON-PATENT LITERATURE DOCUMENTS, Erammer | induce rare othe alhor fn GAPITAL LETTERS), te fhe aril when appropiate), leo the hem (bak, magazine, joural, Irae ‘seal, symposium, extsog, te dale, pages), voume tue numbers), pubisher, ty andlor county where publishes, IXiao ef al, “Chromosomal deletions and inversions mediated by TALENs and CRISPRICas in zebrafish,” IWuol. Acid Res., 1(14), e141; ePub: (2013) Lemay, etal, "Folding of the Adenine Bioswitch, Chemisty & Biology 18.887-68 (2006) Spinoza, ef a. 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