IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In Re:
`
`Issued:
`
`Ex Parte Reexamination of U.S. Patent No. 11,634,781
`
`April 25, 2023
`
`App. Ser. No.:
`
`17/936,335
`
`Filing Date:
`
`September28, 2022
`
`Named Inventor:
`
`Joost Louwagie
`
`Title:
`
`FECAL SAMPLE PROCESSING AND ANALYSIS COMPRISING
`
`DETECTION OF BLOOD
`
`Mail Stop: Ex Parte Reexam
`Commissionerfor Patents
`
`P.O. Box 1450
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`Alexandria, VA 22313-1450
`
`REQUEST FOR EX PARTE REEXAMINATION UNDER 37 C.E.R.
`
`Dear Commissioner:
`
`Ex parte reexamination under 35 U.S.C. §§ 302-307 and 37 C.F.R. § 1.510 is requested
`
`of U.S. Patent No. 11,634,781 (“the ‘781 Patent’). Reexamination is requested of claims 1-20 as
`
`these claimsare anticipated and/or obvious in view ofthe prior art identified in the citation of
`
`prior art under 37 C.F.R. §1.501 submitted herewith. The Rule 501 citation includes a PTO form
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`PTO/SB/08aand copiesofall prior art relied upon.
`
`Requestor, as confirmed by the undersigned attorney, hereby certifies that the statutory
`
`estoppel provisions of 35 U.S.C. § 315(e)(1) and 35 U.S.C. § 325(e)(1) do not prohibit Requester
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`from filing this ex parte reexamination request.
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`Geneoscopy Exhibit 1021, Page 1
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`Geneoscopy Exhibit 1021, Page 1
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`Request for Ex Parte Reexamination of U.S. Patent No. 11,634,781
`
`Table of Contents
`
`Page
`
`ki
`
`Il.
`
`I.
`
`IV.
`
`Identification of Claims for Which Reexamination is Requested 0.0.0.0...eee 1
`
`Overview. of the“781, Patent:s.ai ccnaeran adaans 1
`
`A. Summary of the Independent Claims... ..0..c.ceccceeeeceeeeceeeceeeceereeereeeneesneesneeseeeseneeeeeeeres ]
`
`B. The ‘781 Patent Prosecution History Lacks Any Prior Art Rejections.......0000000000..0.1
`
`The Level of Ordinary Skill itt the Att sccescccsscsccoscoccsascsswssewae neces vasawaonensecuscnaes sacaranauaneareenens 2
`
`Clatint CONSTCHORE ccisccseveccasiereresnivereenecsawecieiseiiave auinantec ana aT reeecTs 3
`
`Pes,
`
`SEV ARIS TOD sas cencncvacesussessnnpsnanaeawnsay eaaeusdinssicussens ase ah eauusay rea saauairasnasanese aan taausayreaniavawaraannss 3
`
`Ben REA AG acccwsninexessnnsia cessnencsnnsegnaanoacena cine balan ins ppaaR OO niceNaN EK RH ERIR 5
`
`Vv.
`
`Other Supporting Evidence ...........ccceceeeesececeeceeeecaeceaeeeseeeeeeseceeeceeneeeneesneeseeceseeeeneeeneseeeeeeees 5
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`A. Declaration of Mr. Anthony P. Shuber, MS.00..0.0.. cece eee eect ecee cess cesses eesneeeeneaeees 5
`
`VI.
`
`Statement Pointing Out Each Substantial New Question of Patentability .......00000 eee 6
`
`A. Lapidus °178 oo... cee ceec cece ecee cee eecnseece see sensaeeneeeeeeseeeaeeesaaeseeaaeseeeeeseaeseeseeeteeesseeereeee LO
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`B. Lapidus ‘650.00... eeceeceeecceecceeeceesceeneeteceeeee tose seneseneseneeseeeseeseeeseesseeeseeeseeeeteerseneeentenarenaees 14
`
`C. Lapidus ‘178 in view of De Luca and Olson... .eeeeececeeeceeeeceeesceseeaeensetecneeeeeeaeensees 14
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`DB, Lapidus 650 in view:of De Lica and Olson éissescsse ennaican 15
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`E.: Ahlquist wn view of De Luca and' OlsOnessscsasicecsccntinc seinciation eek 15
`
`B:
`
`‘O'Neill in view of De Lued and Olson sc. ewan ance syne aninai ena 15
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`G. Lapidus ‘178 in view of De Luca, Olson, and Leung ......00... 2. eee eee eects 16
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`H. Lapidus ‘650 in view of De Luca, Olson, and Leung .00..0....eeceeeceetceeeeeeeeeeeeeeeeeteeeeeneeees 16
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`I. Ahlquist in view of De Luca, Olson, and Leung 2.0.2.0... cceeeceeeeceeceeeeeeeeeeeeeeeeeseeeeeeeees 16
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`J. O'Neill in view of De Luca, Olson, and Leung... ceeeceecesseessteeseeesseessaeseeeee 17
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`K. Lapidus ‘178 in view of De Luca, Olson, and Hoepffnet............00....eceeseeseeeeeeerteetees 17
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`L. Lapidus “650 in view of De Luca, Olson, and Hoepffiner an... cece see eeeeeeeeeeeeeees 17
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`M. Ahlquist in view of De Luca, Olson, and Hoepffiner «.......0....... ee eceeceseeeteceteeeeeteteeeeeeteees 18
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`N. O'Neill in view of De Luca, Olson, and Hoepffner................2:::cccesceeseeeeseeeeeetteeseeenees 18
`
`VIL.
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`Detailed Explanation under 37 C.F.R. § 1S 1O(D) oo... cee cecceeeceee cece ceeeeeeeeeeeeeeeeeenereneeeeaeenaees 18
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`Pee TIREDTICLEGLaLiL cll uemmemettnenen een vecnestaettrenett senrettermertereeeter tre tmestrersrnrettnenert starts tra eter eer 23
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`B. Dependent Claim 2 o....ceeceeeceeeceeeceeeceseneeseeeeseeeeceseeeeeeececeaeeeaaeesaeesaeesaeseaeeeaeeeeeeeeenenenes 108
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`C. Dependent Claim 3 ...........ccccccccccescececececceesceseeeesceeseeeseeeeecesecesseeseeseeeseeesstessttetttestreeeeee LIA
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`D. Dependent Claim 4 oo... eee eeceeeceeeceeeceseneeeeee senses eeeeeeeeeeeeeecaeeeaeeesaecaeenaeeeaeeenaeenaeeneenenene 185
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`E.. Dependent CLAIM5......-..snsseneeesncesarssnsersetnsaregenassestanidetinesen messarenancsennsinntenseeansennesoentes 196
`
`il
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`Request for Ex Parte Reexamination of U.S. Patent No. 11,634,781
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`F. Dependent Claim 6 ......cc.ccccccceccsccceeseseseeeeececeeseeeseeesceeeeeesseeeseeeseecsaesaeseseeeseesseeseeeseeees 201
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`G. Dependent Claim 7.00....eeeeeeeeecesccesceeneeeeeceeeceaeceaeeeaeeesecesecneseveneeeneeeneeseeeeteeeeneseneenense 204
`
`H.. Dependent (laine 8. ......-ssoccseseenasessnnsnennonssnnennd snadetaendiestnataennseanenenas tnnadesnendaennastaeneceanes 207
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`I; Dependent Claim 9 giscccaossesnena een aRae en aaaa is 211
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`Je Dependent Clan 10 scsasssscscessscanvensncaaancaeentin inane eee Staee 217
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`Kk Dependent Claim 17 sinensisuaenrSeee zee 221
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`Ls: Dependent Chany 12 wscsssscceescssccassasscasen ceases tasaucvies sigue vag cas a itia ia sae eavieas Coins eae 225
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`M? Dependent Glam 13 acencess cones vacaeas 237
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`N:: Dependent Clair 14 siscsc.scssivsvssvasisncscsnasenaseeiv vasatncersvacievasearanacetnnnnieeis 210
`
`@. Deperidetit Claim TS scsocncccascoccssensseesrerscacsaseacctascusn aanasucerv eave easatuse maser DOO)
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`PB: Depeiiclent ai Gi csc casesiw oes ceversavercavzeuncsmecsz aisanerscunave tomas saateedeeievateeulrenveccaviaueces 260
`
`@., Deperident Gia17 crscnsescescssveecusasseauscusensrasaseussousuyeewusapncatuctnsecvade ts ese seuewataysencuausenceas 265
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`R. Dependent Claim 18 .......cccccccccccccesccsscescestssseeecescesseeaseseceaesaeseccaecsseeaeeeceseseceeeeeseeseeeess 269
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`S. Dependent Claim 19 20.0... ceceeccceeceescecececneeceaeseaeeeaeeeaeeeeeeesecnenceeneeeneeseeeseeeteneseneseeeneees 273
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`T. Dependent Claim 20 ........cccccccceseesecsceeeeceaeeeaeeeaeeeaeeeeeesecneneeeneeeneeseeeseeeeeeeseneseeeneess 278
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`VII.
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`COmnClUSiON oo... cee cece cece cece cece cee sesceesceeeceacecsceceaccaaeceaeesaeeesceesceeseceseceseceeeeeseeesaeeseeeseseseaeeesees 282
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`lil
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`Request for Ex Parte Reexamination of U.S. Patent No. 11,634,781
`
`Exhibits
`
`Exhibit 1001:
`
`U.S. Patent No. 11,634,781 (“the ‘781 Patent’)
`
`Exhibit 1002:
`
`U.S. Patent No. 5,952,178 to Lapiduset al. (“Lapidus ‘178”)
`
`Exhibit 1003:
`
`U.S. Patent No. 5,741,650 to Lapidusetal. (“Lapidus “650”)
`
`Exhibit 1004:
`
`Ahlquist et al., “Stool DNA and Occult Blood Testing for Screen Detection of
`Colorectal Neoplasia,” Ann Intern Med., 149(7):441-W81 (published in final form
`October 7, 2008) (“Ahlquist’”’)
`
`Exhibit 1005:
`
`Patent Cooperation Treaty (PCT) Publication No. WO 2005/014154 to O’Neill
`(“O’ Neill”)
`
`Exhibit 1006:
`
`European Patent Application Publication No. EP1366715A1 to De Lucaetal.
`(“De Luca”)
`
`Exhibit 1007:
`
`Olson et al., “DNA Stabilization Is Critical for Maximizing Performance of Fecal
`DNA-Based Colorectal Cancer Tests,” Diagn Mol Pathol, 14:183-191 (published
`September 2005) (“Olson’’)
`
`Exhibit 1008:
`
`Leunget al., “Detection of Hypermethylated DNA or Cyclooxygenase-2
`Messenger RNAin Fecal Samples of Patients With Colorectal Cancer or
`Polyps,” Am J Gastroenterol, 102:1070—1076 (2007) (“Leung”)
`
`Exhibit 1009:
`
`Hoepffneret al., “Comparative evaluation of a new bedside faecal occult blood
`test in a prospective multicentre study,” Aliment Pharmacol Ther, 23, 145-154
`(published 2006) (“Hoepffner’”’)
`
`Exhibit 1010:
`
`U.S. Patent No. 4,859,610 to Maggio (“Maggio”)
`
`Exhibit 1011:
`
`U.S. Patent No. 5,196,167 to Guandagnoetal. (“Guandagno”’)
`
`Exhibit 1012:
`
`U.S. Patent No. 5,137,806 to LeMaistre et al. (“LeMaistre’’)
`
`Exhibit 1013:
`
`U.S. Patent No. 5,527,676 to Vogelstein et al. (“Vogelstein’’)
`
`Exhibit 1014:
`
`Declaration of Mr. Anthony P. Shuber, MS
`
`1V
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`Geneoscopy Exhibit 1021, Page 4
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`Geneoscopy Exhibit 1021, Page 4
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`I.
`
`Identification of Claims for Which Reexamination is Requested
`
`In accordance with 37 C.F.R. § 1.510, reexamination of claims 1-20 of the ‘781 Patent is
`
`requested, in view ofthe referencescited herein.
`
`II.
`
`Overview of the ‘781 Patent
`
`A. Summaryof the Independent Claims
`
`The ‘781 Patent issued on April 25, 2023 and includes one independent claim. As
`
`discussed below, independent claim | and its respective dependent claims are knownin the prior
`
`art.
`
`Claim | is the sole independent claim as shown below:
`
`Bs
`
`A method ofprocessing a freshly-collected fecal sample without freezing, the
`
`method comprising:
`
`a) collecting a fecal sample from a human subject, wherein the fecal sample is
`
`collected at home by the humansubject by defecation directly into a sealable collection
`
`vessel;
`
`b) removing a portion of the fecal sample to a separate sealable container to
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`produce a removed portion and a remaining portion of the fecal sample;
`
`c) combining the removed portion of the fecal sample in the separate sealable
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`container with a buffer that prevents denaturation or degradation of blood proteins found
`
`in a fecal sample, and sealing the sealable container; and
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`d) combining the remaining portion of the fecal sample in the sealable collection
`
`vessel with a stabilizing buffer, and sealing the sealable collection vessel.
`
`B. The ‘781 Patent Prosecution History Lacks Any Prior Art Rejections
`
`The application for the “781 Patent wasfiled by Exact Sciences Corporation on
`
`September 28, 2022. As shownonthe face of the *781 Patent (Ex. 1001), the ‘781 Patent claims
`
`priority to 1) U.S. Patent Application No. 15/634,607, filed June 27, 2017, ii) U.S. Patent
`
`Application No. 15/010,436, filed January 29, 2016, iii) U.S. Patent Application No. 13/147,570,
`
`filed March 12, 2012, iv) PCT International Application No. PCT/GB2010/000180,filed
`
`February 3, 2010, and v) U.S. Provisional Patent Application No. 61/149,581, filed February 3,
`
`2009.
`
`Geneoscopy Exhibit 1021, Page 5
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`Geneoscopy Exhibit 1021, Page 5
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`The Office examined the application that resulted in the ‘781 Patent under the pre-AIA
`
`“first to invent” provisions as stated in the prosecution history of the “781 Patent. Requestor
`
`does not concede that the “781 Patent should be afforded this status but provides the anticipation
`
`and obviousnessassertions herein according to the pre-AIA “first to invent” provisions as
`
`determined by the Office. However,if the “781 Patent is subject to the AIA’s “first inventor to
`
`file” provisions, then Requestornotes that each prior art reference cited herein would qualify as
`
`prior art under AJA 35 U.S.C. § 102(a)(1).
`
`Notably, the prosecution history of the application that resulted in the “781 Patentis
`
`completely devoid of prior-art based rejections, other than a provisional nonstatutory double
`
`patenting rejection over a co-pending Exact Sciences application related to the *781 Patent(i.e.,
`
`co-pending U.S. Patent Application No. 15/634,607) and a provisional nonstatutory double
`
`patenting rejection over the co-pending Exact Sciences application in view of Ohlssonet al. (Br J
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`Cancer, 2006; 95(2):218—225). The provisional nonstatutory double patenting rejections were
`
`made in an Office Action issued on January 11, 2023.
`
`In response, the applicantfiled a Terminal
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`Disclaimer on January 24, 2023. Thereafter, the provisional nonstatutory double patenting
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`rejections were withdrawn.
`
`The application was subsequently allowed on February 16, 2023. On pages 2-3 of the
`
`Notice of Allowance, the Examiner provided a statement of reasons for allowance,the entirety of
`
`which is quoted below:
`
`Claim(s) 1-20 is/are deemed to be allowable in light of the paper(s) filed 23
`JAN 2023 and the persuasive argument(s) therein.
`
`The application subsequently issued as the ‘781 Patent on April 25, 2023. Ex. 1001. As
`
`discussed below, the claimed subject matter in the *781 Patent was known in the priorart and
`
`lacks novelty and/or would have been obviousto one of ordinary skill in the art.
`
`II.
`
`The Level of Ordinary Skill in the Art
`
`Asset forth above, the ‘781 Patent issued from an application claiming priority from a
`
`provisional application filed on February 3, 2009. As such, the earliest possible effective filing
`
`date that could be accorded the “781 Patent is February 3, 2009. Requestor does not concedethat
`
`any orall claims of the *781 Patent should be afforded an effective filing date of February 3,
`
`2009, but has nevertheless treated this date as the effective filing date of all claims solely for
`
`purposesof this Request.
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`The relevantfield of “the invention of the *781 Patentis the field of processing and
`
`evaluating fecal samples. Ex. 1014 at paragraph 18. A personof ordinary skill in this field:
`
`would havehadat least a Bachelor of Science degree in Biology (or a
`similar major) and several years of experience in the processing of
`biological samples, such as fecal samples from a human. Such a person
`would have been well-acquainted with methodsofcollecting fecal
`samples, preserving proteins and/or nucleic acids, including hemoglobin,
`DNA, and RNA, and subsequently evaluating the fecal samples for
`proteins and/or nucleic acids, including hemoglobin, DNA, and RNA,as
`of February 3, 2009.
`
`Id. at paragraph 20.
`
`IV.
`
`Claim Construction
`
`During reexamination, claims are given the broadest reasonable interpretation consistent
`
`with the specification and limitations in the specification are not read into the claims. MPEP §
`
`2258.
`
`A. Claims 1-20
`
`1. The Preamble of Independent Claim 1 is Not a Limitation
`
`Requestor respectfully submits that the preamble of claim 1 is not a limitation. The
`
`Federal Circuit has held:
`
`In general, a preamble limits the inventionif it recites essential structure orsteps,
`or if it is necessary to give life, meaning, and vitality to the claim. Conversely, a
`preambleis not limiting where a patentee defines a structurally complete
`invention in the claim body and uses the preamble only to state a purpose or
`intended use for the invention. No litmustest defines when a preamble limits
`claim scope. Some guideposts, however, have emerged from various cases
`discussing the preamble's effect on claim scope. For example, this court has held
`that Jepson claiming generally indicates intent to use the preamble to define the
`claimed invention, thereby limiting claim scope. Additionally, dependence on a
`particular disputed preamble phrase for antecedent basis may limit claim scope
`becauseit indicates a reliance on both the preamble and claim body to define the
`claimed invention. Likewise, when the preamble is essential to understand
`limitations or terms in the claim body, the preamble limits claim scope. Further,
`whenreciting additional structure or steps underscored as important by the
`specification, the preamble mayoperate as a claim limitation. Moreover, clear
`reliance on the preamble during prosecution to distinguish the claimed invention
`from the prior art transforms the preambleinto a claim limitation because such
`reliance indicates use of the preamble to define, in part, the claimed invention.
`Without such reliance, however, a preamble generally is not limiting when the
`claim body describesa structurally complete invention such that deletion of the
`
`3
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`preamble phrase does notaffect the structure or steps of the claimed invention.
`Thus, preamble language merely extolling benefits or features of the claimed
`invention does not limit the claim scope without clear reliance on those benefits
`or features as patentably significant.
`
`Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 808-09 (Fed. Cir. 2002)
`
`(internal quotations and citations omitted).
`
`The preamble of claim 1 of the ‘781 Patent does not recite any essential structure or steps
`
`and is not necessary to give life, meaning,or vitality to the claim. Instead, claim 1 defines a
`
`complete method in the claim body and uses the preamble only to state a purpose or intended use
`
`for the alleged invention. Further, claim 1 of the ‘781 Patent is not drafted in Jepson format.
`
`Additionally, the preamble of claim 1 of the “781 Patent does not establish dependence on a
`
`particular disputed preamble phrase for antecedentbasis as there is no apparent reliance on both
`
`the preamble and claim bodyto define the claimed invention,noris the preamble of claim | of
`
`the ‘781 Patent essential to understand limitations or terms in the claim body. The preamble of
`
`claim | of the “781 Patent does not recite additional structure or steps underscored as important
`
`by the specification. Finally, there is no clear reliance on the preamble of claim 1 of the ‘781
`
`Patent during prosecution to distinguish the claimed invention from the prior art.
`
`In summary,
`
`the preamble of claim | of the ‘781 Patent merely extols benefits or features of the claimed
`
`invention and Requestorasserts that the preamble of claim 1 is not a limitation.
`
`2. “Without Freezing” Refers to a Temperature or Temperature Range Above
`0°C (32°F)
`
`All claims require that a fecal sample is processed “without freezing.” The ordinary
`
`meaning of “freezing” is “being at or below the temperature at which water freezes” according to
`
`Merriam-Webster’s Medical Dictionary (available at https://www.merriam-
`
`webster.com/dictionary/freezing). The temperature at which water freezes is knownto be 0°C
`
`(32°F). Ex. 1014 at paragraph 27. Therefore, any temperature above 0°C (32°F), ora
`
`temperature range that includes a temperature above 0°C (32°F), would be understood as
`
`“without freezing” by those of ordinary skill in the art. Jd.
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`Geneoscopy Exhibit 1021, Page 8
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`3.
`
`“At Home” Refers to a Location Other Than a Testing Facility
`
`All claims require that the fecal sample is collected “at home.” The *781 Patent uses this
`
`term primarily to distinguish the location of collection fromthetesting facility. For instance, the
`
`‘781 Patentstates that “[f]ollowing collection of the sample and suitable processing, the method
`
`may further comprise forwarding or otherwise delivering the removed portion ofthe collected
`
`faecal sample to_a laboratoryfor performing step (a) of the method, as defined herein, on the
`
`removedportion of the collected faecal sample.” /d. at column 18, lines 32-35 (emphasis
`
`added). Similarly, dependent claim 2 of the ‘781 Patent indicates that the method of claim 1
`
`[further comprises “delivering the [fecal sample collected at home] to a medical diagnostics
`
`laboratory.” /d. at column 45, lines 39-44,
`
`Therefore, a person ofordinary skill in the art would understood “at home”, as used in the
`
`‘781 Patent, to refer to a location other than the testing facility. Ex. 1014 at paragraph 28.
`
`B. Claims 5-11
`
`1. “Epigenetic Modification”is an Alteration in DNA
`
`Regarding claims 5-11, the ‘781 Patent defines “epigenetic modification” such thatit
`
`includes “any alteration in the DNA,generally resulting in diminished gene expression, which is
`
`mediated by mechanismsother than alterations in the primary nucleotide sequenceof a gene.”
`
`Ex. 1001 at column 12, lines 35-39. Forinstance, the “781 patent describes that “[i]n specific
`
`embodiments, the epigenetic modification is methylation.” /d. at column 12, line 46-47. This
`
`definition of “epigenetic modification” provided by the “781 Patent is consistent with the
`
`definition of “epigenetic modification” as understood by those of ordinary skill in the art. Ex.
`
`1014 at paragraph 29.
`
`X.
`
`Other Supporting Evidence
`
`A. Declaration of Mr. Anthony P. Shuber, MS
`
`The Declaration of Mr. Anthony P. Shuber, MSis being submitted with this Request as
`
`Exhibit 1014 to “explain the contents or pertinent dates of prior art patents or printed
`
`publications in more detail.” See MPEP § 2258(1)(E). Mr. Shuber has extensive experience in
`
`the fields of diagnostics and applied genomics, including a Bachelor of Science degree in
`
`Biology and a Master of Science degree in Molecular and Developmental Biology from
`
`5
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`Geneoscopy Exhibit 1021, Page 9
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`Marquette University in Milwaukee, Wisconsin. See Mr. Anthony P. Shuber curriculum vitae
`
`(Ex. 1014).
`
`Mr. Shuber’s work in the field includes developing several DNA diagnosticstests as well
`
`as diagnostics in oncology, with a focus on the early detection of cancer. Heis currently the
`
`Chief Innovation Officer at Harbinger Health. Mr. Shuberis a named inventor or author on
`
`several prior art references cited herein, including Ex. 1002, Ex. 1003, and Ex. 1007.
`
`His declaration provides factual evidence regarding the level of skill in the art, the prior
`
`art references, the scope and contentofthe prior art, and technical information relevant to the
`
`‘781 Patent, as well as explaining why the claimed invention would have been obviousto a
`
`person of ordinary skill in theart.
`
`VI.
`
`Statement Pointing Out Each Substantial New Question of Patentability
`
`This Section addresses the substantial new questions of patentability and is organized by
`
`cited references.
`
`As explained above,the Office did not issue prior art-based rejections during the
`
`examination that resulted in the “781 Patent. Moreover, with the exception of O’ Neill, none of
`
`the prior art references identified below and discussed herein were cited by the Patentee or by
`
`the Office in the course of examination that resulted in the ‘781 Patent. Although O’Neill was
`
`cited by the Patentee, it was not utilized in any prior-art based rejection during the examination
`
`that resulted in the ‘781 Patent.
`
`Accordingly, the following prior art references (except O’Neill) are newly cited in this
`
`reexamination request and raise substantial new questions of patentability because they are
`
`highly relevant to the claims of the ‘781 Patent as shown belowand havenot been substantively
`
`considered by the USPTO:
`
`
`
`
`Ex. No.Prior Art Citation Summary
`
`U.S. Patent No. 5,952,178 to 1002|Lapidus ‘178 is a granted U.S. patent and discloses
`
`Lapiduset al. (“Lapidus
`
`methods for processing and testing a fecal sample,
`
`
`
`
`
`178”)
`
`including evaluation of proteins and nucleic acids.
`
`Id. at, e.g., column 7, line 59 — column9,line 50.
`
`Fecal samples are collected from a human subject,
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`Geneoscopy Exhibit 1021, Page 10
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`Geneoscopy Exhibit 1021, Page 10
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`
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`separated into two or more portions, and combined
`
`with buffers. Lapidus “178 was patented on
`
`September 14, 1999 and therefore is prior art under
`
`claims.
`
`U.S. Patent No. 5.741.650 to
`
`1003
`
`Lapidus “650 is a granted U.S. patent and discloses
`
`pre-AIA 35 U.S.C. § 102(b) against the challenged
`
`Lapiduset al. (“Lapidus
`
`methods for processing and testing a fecal sample,
`
`*650”)
`
`including evaluation of proteins and nucleic acids.
`
`Id. at, e.g., column 7, line 12 — column8, line 25.
`
`Fecal samples are collected from a human subject,
`
`separated into two or more portions, and combined
`
`with buffers. Lapidus “650 was patented on April
`
`35 U.S.C. § 102(b) against the challenged claims.
`
`Ahlquist et al., “Stool DNA
`
`1004
`
`Ahlquistis a journal article and discloses
`
`21, 1998 and therefore is prior art under pre-AIA
`
`and Occult Blood Testing for
`
`collection of stool and comparison of stool DNA
`
`Screen Detection of
`
`and fecal blood testing for detection of colorectal
`
`Colorectal Neoplasia,” Ann
`
`neoplasia.
`
`/d. at Abstract. Fecal samples are
`
`Intern Med., 149(7):441-W81
`
`collected from a humansubject, separated into two
`
`(published in final form
`
`October 7, 2008)
`
`(“Ahlquist’’)
`
`or more portions, and analyzed for both nucleic
`
`acids and blood proteins. Ahlquist was published
`
`
`
`
`
`and publicly available at least as early as October 7,
`
`2008. Ex. 1014 at paragraph 37. Therefore,
`
`Patent Cooperation Treaty
`
`1005
`
`O’Neill is a published PCT application and
`
`U.S.C. § 102(a) against the challenged claims.
`
`Ahlquistis at least prior art under pre-AIA 35
`
`(PCT) Publication No. WO
`
`discloses a method of removing cellular material
`
`2005/014154 to O’Neill
`
`from the surface of a fecal stool in a container. Jd.
`
`(“ONeill”)
`
`at Abstract. The patient collects a fecal sample at
`
`homebydefecation directly into a sealable
`
`container and then a portion of the fecal sample
`
`Geneoscopy Exhibit 1021, Page 11
`
`Geneoscopy Exhibit 1021, Page 11
`
`

`

`
`
`(cellular material) is removed for analysis of DNA,
`
`RNA,proteins, and the like. O’Neill was published
`
`and publicly available on February 17, 2005, and
`
`therefore is at least prior art under pre-AIA 35
`
`U.S.C. § 102(b) against the challenged claims.
`
`1006|De Lucais a published Europeanpatent application
`
`Publication No.
`
`and discloses an extraction tube for collection of
`
`EP1366715A1 to De Lucaet
`
`fecal samples and combination with a buffer.
`
`/d. at
`
`al. (“De Luca”)
`
`[0019]. The extraction tube contains a sealable cap
`
`and the tubeis utilized for laboratory
`
`immunological tests, such as for qualitative or
`
`quantitative determination of hemoglobin. De Luca
`
`waspublished and publicly available on December
`
`claims.
`
`
`
`
`Olsonet al.,“DNA 1007|Olsonis a journal article and discloses collection of
`
`AIA 35 U.S.C. § 102(b) against the challenged
`
`3, 2003, and therefore is at least prior art under pre-
`
`Stabilization Is Critical for
`
`stool and detection of fecal DNA. Jd. at Abstract.
`
`Maximizing Performance of
`
`Fecal samples are collected from a human subject
`
`Fecal DNA-Based Colorectal
`
`and a stabilizing buffer was added to the samples.
`
`Cancer Tests,” Diagn Mol
`
`Addition ofthe stabilizing buffer was shownto
`
`Pathol, 14:183-191
`
`provide a significant increase in recovery of DNA
`
`(published September 2005)
`
`from fecal samples.
`
`/d. Olson was published and
`
`
`
` European Patent Application subject and analyzed for hypermethylated DNA via
`
`(“Olson”)
`
`publicly available in September 2005. Ex. 1014 at
`
`
`
`Leunget al., “Detection of 1008|Leungis a journalarticle and discloses collection
`
`challenged claims.
`
`under pre-AIA 35 U.S.C. § 102(b) against the
`
`paragraph 40. Therefore, Olsonis at least priorart
`
`Hypermethylated DNA or
`
`of stool and detection of fecal DNA. Jd. at
`
`Cyclooxygenase-2 Messenger
`
`Abstract. Fecal samples are collected from a human
`
`RNAin Fecal Samples of
`
`Geneoscopy Exhibit 1021, Page 12
`
`Geneoscopy Exhibit 1021, Page 12
`
`

`

`
`
`(published 2006)
`
`(“Hoepffner’’)
`
`in nanograms/milliliter (ng/ml) resulting in a
`
`positive blood test in fecal samples is discussed.
`
`Hoepffner was published and publicly available in
`
`2006. Ex. 1014 at paragraph 42. Therefore,
`
`Hoepffneris at least prior art under pre-AJA 35
`
`U.S.C. § 102(b) against the challenged claims.
`
`U.S. Patent No. 4,859,610 to
`
`1010
`
`Maggiois a granted U.S. patent and discloses a
`
`Maggio (“Maggio’’)
`
`device that is used for homogenizing and analyzing
`
`fecal samples.
`
`/d. at, e.g., column4,lines 7-8.
`
`Fecal sample and phosphate buffered saline are
`
`homogenizedin a separate sealable container(i.e.,
`
`vessel) that contains a cap and seal. Maggio was
`
`patented on August 22, 1989 and thereforeis prior
`
`art under pre-AIA 35 U.S.C. § 102(b) against the
`
`challenged claims. Maggiois cited herein as an
`
`evidentiary reference only.
`
`
`
`Patients With Colorectal
`
`PCR and for mRNA via RT-PCR. Leung was
`
`Cancer or Polyps,” Am J
`
`published and publicly available in 2007. Ex. 1014
`
`Gastroenterol, 102:1070—
`
`at paragraph 41. Therefore, Leungis at least prior
`
`1076 (2007) (“Leung”)
`
`art under pre-AJA 35 U.S.C. § 102(b) against the
`
`challenged claims.
`
`Hoepffneretal.,
`
`1009
`
`Hoepffneris a journal article and discloses a
`
`“Comparative evaluation of a
`
`comparison of characteristics of a new bedside
`
`new bedside faecal occult
`
`immunologicaltest strip device with a sensitive
`
`blood test in a prospective
`
`Guaiac-based andestablished immunochemicaltest
`
`multicentre study,” Aliment
`
`for detection of faecal occult blood in patients.
`
`Pharmacol Ther, 23, 145-154
`
`Id. at Abstract. The concentrations of hemoglobin
`
`
`
`This Request seeks reexamination based on the following proposed rejectionsthat raise
`
`substantial new questions of patentability for all claims of the “781 Patent. The specific
`
`application of the newly cited prior art references to such claimsis detailed in Section VII:
`
`9
`
`Geneoscopy Exhibit 1021, Page 13
`
`Geneoscopy Exhibit 1021, Page 13
`
`

`

`
`
`Prior Art Rendering Claims Anticipated Under 35 USC § 102(b)
`
`1
`
`Lapidus ‘178 (Ex. 1002)
`
`
`Lapidus *650 (Ex. 1003)
`
`
`Lapidus *178
`
`
`Lapidus ‘650
`
`
` Claim
`
`
`
`
`
`2
`
`3
`
`4
`
`Lapidus ‘178
`
`Lapidus ‘650
`
`Lapidus ‘178
`
`
`Lapidus ‘650
`
`
`12‘|Lapidus ‘178
`
`
`Lapidus ‘650
`
`
`Claim
`
`Prior Art Combinations Rendering Claims Obvious Under 35 USC § 103(a)
`
`1
`
`Lapidus “178
`
`
`Lapidus ‘650
`
`
`Lapidus ‘178 in view of De Luca (Ex. 1006) and Olson (Ex. 1007)
`
`
`Lapidus ‘650 in view of De Luca and Olson
`
`
`Ahlquist (Ex. 1004) in view of De Luca and Olson
`
`
`O'Neill (Ex. 1005) in view of De Luca and Olson
`
`2
`
`Lapidus ‘178
`
`
`Lapidus “650
`
`
`Lapidus ‘178 in view of De Luca and Olson
`
`
`Lapidus ‘650 in view of De Luca and Olson
`
`
`Ahlquist in view of De Luca and Olson
`
`
`O’ Neill in view of De Luca and Olson
`
`3
`
`Lapidus ‘178
`
`Lapidus ‘650
`
`
`Lapidus ‘178 in view of De Luca and Olson
`
`Lapidus ‘650 in view of De Luca and Olson
`
`10
`
`Geneoscopy Exhibit 1021, Page 14
`
`Geneoscopy Exhibit 1021, Page 14
`
`

`

`
`
`Ahlquist in view of De Luca and Olson
`
`O’ Neill in view of De Luca and Olson
`
`Lapidus ‘178
`
`Lapidus *650
`
`Lapidus ‘178 in view of De Luca and Olson
`
`Lapidus ‘650 in view of De Luca and Olson
`
`Ahlquist in view of De Luca and Olson
`
`O’Neill in view of De Luca and Olson
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca and Olson
`
`
`
`O’Neill in view of De Luca, Olson, and Leung Lapidus ‘178 in view of De Luca, Olson, and Leung Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`
`
`O’Neill in view of De Luca, Olson, and Leung
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca and Olson
`
`O’Neill in view of De Luca, Olson, and Leung
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’Neill in view of De Luca, Olson, and Leung
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’Neill in view of De Luca, Olson, and Leung
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus “650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`10
`
`La
`
`Geneoscopy Exhibit 1021, Page 15
`
`Geneoscopy Exhibit 1021, Page 15
`
`

`

`
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’ Neill in view of De Luca, Olson, and Leung
`
`11
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’Neill in view of De Luca, Olson, and Leung
`
`12
`
`Lapidus ‘178
`
`Lapidus ‘650
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’Neill in view of De Luca, Olson, and Leung
`
`13
`
`Lapidus ‘178 in view of De Luca, Olson, and Leung
`
`Lapidus ‘650 in view of De Luca, Olson, and Leung
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’Neill in view of De Luca, Olson, and Leung
`
`14
`
`Lapidus ‘178 in view of De Luca and Olson
`
`Lapidus ‘650 in view of De Luca and Olson
`
`Ahlquist in view of De Luca, Olson, and Leung
`
`O’ Neill in view of De Luca and Olson
`
`15
`
`Lapidus ‘178 in view of De Luca and Olson
`
`Lapidus ‘650 in view of De Luca and Olson
`
`Ahlquist in view of De Luca and Olson
`
`O’ Neill in view of De Luca and Olson
`
`16
`
`Lapidus ‘178 in view of De Luca, Olson, and Hoepffner (Ex. 1009)
`
`Lapidus “650 in view of De Luca, Olson, and Hoepffner
`
`Ahlquist in view of De Luca, Olson, and Hoepffner
`
`
`
`O’Neill in view of De Luca, Olson, and Hoepffner Lapidus ‘178 in view of De Luca, Olson, and Hoepffner Lapidus ‘650 in view of De Luca, Olson, and Hoepffner
`
`
`
`17
`
`12
`
`Geneoscopy Exhibit 1021, Page 16
`
`Geneoscopy Exhibit 1