`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`GENEOSCOPY, INC.,
`Petitioner,
`
`v.
`
`EXACT SCIENCES CORPORATION,
`Patent Owner.
`____________
`
`Case No.: IPR2024-00459
`U.S. Patent 11,634,781
`____________
`
`
`PETITION FOR INTER PARTIES REVIEW
`OF U.S. PATENT 11,634,781
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`V.
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`TABLE OF CONTENTS
`Introduction .......................................................................................... 1
`I.
`STANDING AND PROCEDURAL STATEMENTS ......................... 2
`II.
`III. MANDATORY NOTICES & PROCEDURAL STATEMENTS ....... 2
`A.
`Real Party-in-Interest, 37 C.F.R. § 42.8(b)(1) ........................... 2
`B.
`Related Matters, 37 C.F.R. § 42.8(b)(2) .................................... 2
`C.
`Lead and Backup Counsel and Service Information, 37
`C.F.R. § 42.8(b)(3) and (b)(4) .................................................... 3
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`THE REASONS THEREFOR, 37 C.F.R. § 42.22(a) .......................... 4
`BACKGROUND .................................................................................. 4
`A.
`Technical Background ............................................................... 4
`1.
`Sample Collection and Preparation ................................. 4
`2.
`Fecal Occult Blood Tests ................................................. 7
`3.
`Fecal Nucleic Acid Tests ................................................. 7
`The ’781 Patent .......................................................................... 9
`B.
`IDENTIFICATION OF THE CHALLENGE, 37 C.F.R. §
`42.104(b) ............................................................................................. 11
`A.
`The Person of Ordinary Skill in the Art ................................... 12
`B.
`References in the Grounds ....................................................... 13
`1.
`Lenhard (EX1004) ......................................................... 13
`2.
`Vilkin (EX1005) ............................................................ 14
`3.
`Itzkowitz (EX1006) ....................................................... 16
`4.
`Kanaoka (EX1007) ........................................................ 17
`5.
`Derks (EX1008) ............................................................. 19
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`VI.
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`IPR2024-00459
`U.S. Patent 11,634,781
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`5.
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`3.
`4.
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`Shuber (EX1009) ........................................................... 19
`6.
`VII. DETAILED EXPLANATION OF THE GROUNDS ........................ 20
`A. Ground I: Lenhard in view of Itzkowitz and Vilkin ................ 20
`1.
`Claim 1 ........................................................................... 26
`2.
`Claim 2: “The method of claim 1, further comprising
`delivering the sealable container containing the
`removed portion of the fecal sample and said buffer
`and the sealable collection vessel containing the
`remaining portion of the fecal sample and said
`stabilizing buffer to a medical diagnostics laboratory” . 32
`Claim 3 ........................................................................... 33
`Claim 4: “The method of claim 3, wherein testing the
`nucleic acid comprises determining expression from
`a human gene.” .............................................................. 36
`Claim 5: “The method of claim 4, wherein
`determining expression from the human gene
`comprises testing the nucleic acid for the presence of
`human DNA having an epigenetic modification.” ........ 37
`Claim 6: “The method of claim 5, wherein testing the
`nucleic acid for the presence of human DNA having
`an epigenetic modification comprises measuring an
`amount of a methylated human DNA.” ......................... 37
`Claim 7: “The method of claim 5, wherein the
`epigenetic modification comprises aberrant
`methylation.” .................................................................. 38
`Claim 8: “The method of claim 7, wherein the
`aberrant methylation comprises hypermethylation.” ..... 38
`Claim 9: “The method of claim 7, wherein the human
`DNA having an epigenetic modification comprises a
`gene and/or a promoter region of a gene.” .................... 39
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`6.
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`7.
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`8.
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`9.
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`10. Claim 11: “The method of claim 5, wherein testing
`the nucleic acid for presence of human DNA having
`an epigenetic modification comprises modifying the
`nucleic acid with bisulfate ions under conditions
`wherein unmethylated cytosine is converted to
`uracil.” ............................................................................ 39
`11. Claim 14: “The method of claim 3, wherein testing
`for an amount of blood protein in the removed
`portion comprises testing for a concentration of
`hemoglobin in the removed portion.” ............................ 40
`12. Claim 15: “The method of claim 14, wherein the
`testing for the concentration of hemoglobin
`comprises immunochemical detection of
`hemoglobin.” .................................................................. 41
`13. Claims 16-20: “The method of claim 14, wherein the
`removed portion of the fecal sample is considered
`positive for the presence of blood when the
`concentration of hemoglobin detected in the removed
`portion is at least [5, 10, 20, 50, or 200] ng/ml.” ........... 41
`B. Ground II: Lenhard in view of Itzkowitz and Vilkin, in
`further view of Kanaoka ........................................................... 43
`1.
`Claim 12: “The method of claim 4, wherein
`determining expression from the human gene
`comprises measuring an amount of RNA expressed
`from the gene.” .............................................................. 43
`Claim 13: “The method of claim 12, wherein
`measuring an amount of RNA expressed from the
`gene comprises reverse transcriptase polymerase
`chain reaction (RT-PCR) ............................................... 45
`C. Ground III: Lenhard in view of Itzkowitz and Vilkin, in
`further view of Derks ............................................................... 46
`D. Ground IV: Shuber and Vilkin ................................................. 47
`1.
`Claim 1 ........................................................................... 51
`
`2.
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`IPR2024-00459
`U.S. Patent 11,634,781
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`2.
`
`5.
`
`3.
`4.
`
`Claim 2: “The method of claim 1, further comprising
`delivering the sealable container containing the
`removed portion of the fecal sample and said buffer
`and the sealable collection vessel containing the
`remaining portion of the fecal sample and said
`stablizing buffer to a medical diagnostics laboratory” .. 55
`Claim 3 ........................................................................... 55
`Claim 4: “The method of claim 3, wherein testing the
`nucleic acid comprises determining expression from
`a human gene.” .............................................................. 58
`Claim 5: “The method of claim 4, wherein
`determining expression from the human gene
`comprises testing the nucleic acid for the presence of
`human DNA having an epigenetic modification.” ........ 58
`Claim 6: “The method of claim 5, wherein testing the
`nucleic acid for the presence of human DNA having
`an epigenetic modification comprises measuring an
`amount of a methylated human DNA.” ......................... 59
`Claim 7: “The method of claim 5, wherein the
`epigenetic modification comprises aberrant
`methylation.” .................................................................. 59
`Claim 8: “The method of claim 7, wherein the
`aberrant methylation comprises hypermethylation.” ..... 59
`Claim 9: “The method of claim 7, wherein the human
`DNA having an epigenetic modification comprises a
`gene and/or a promoter region of a gene.” .................... 60
`10. Claim 11: “The method of claim 5, wherein testing
`the nucleic acid for presence of human DNA having
`an epigenetic modification comprises modifying the
`nucleic acid with bisulfate ions under conditions
`wherein unmethylated cytosine is converted to uracil. . 60
`11. Claim 14: “The method of claim 3, wherein testing
`for an amount of blood protein in the removed
`
`6.
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`7.
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`8.
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`9.
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`U.S. Patent 11,634,781
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`E.
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`portion comprises testing for a concentration of
`hemoglobin in the removed portion.” ............................ 61
`12. Claim 15: “The method of claim 14, wherein the
`testing for the concentration of hemoglobin
`comprises immunochemical detection of
`hemoglobin.” .................................................................. 61
`13. Claims 16-20: “The method of claim 14, wherein the
`removed portion of the fecal sample is considered
`positive for the presence of blood when the
`concentration of hemoglobin detected in the removed
`portion is at least [5, 10, 20, 50, or 200] ng/ml.” ........... 61
`Ground V: Shuber and Vilkin, in further view of Kanaoka ..... 62
`1.
`Claims 12 “The method of claim 4, wherein
`determining expression from the human gene
`comprises measuring an amount of RNA expressed
`from the gene.” .............................................................. 62
`Claim 13: “The method of claim 12, wherein
`measuring an amount of RNA expressed from the
`gene comprises reverse transcriptase polymerase
`chain reaction (RT-PCR) ............................................... 64
`Ground VI: Shuber and Vilkin, in further view of Derks ........ 65
`F.
`VIII. Secondary Considerations of Non-obviousness ................................. 65
`IX. Discretion under 35 U.S.C. § 325(d) .................................................. 66
`X.
`Conclusion .......................................................................................... 67
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`IPR2024-00459
`U.S. Patent 11,634,781
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Advanced Bionics, LLC v. Med-El Elekromedizinische Geräte
`GmbH,
`IPR2019-01469, Paper 6 (P.T.A.B. Feb. 13, 2020) .......................... 66, 67
`Alcon Research, LTD. v. Apotex Inc.,
`687 F.3d 1362 (Fed. Cir. 2012) ............................................................... 36
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) ................................................... 42, 43, 62
`Exact Sciences Corporation v. Geneoscopy, Inc.,
`No. 23-cv-1319-MN (D. Del.) ............................................................... 2, 3
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007)................................................................................. 31
`Satco Products Inc. v. The Regents of the Univ. of California,
`IPR2021-00662, Paper 13 (P.T.A.B. Nov. 8, 2021) ................................ 67
`ZUP, LLC v. Nash Mfg., Inc.,
`896 F.3d 1365 (Fed. Cir. 2018) ............................................................... 65
`Statutes
`35 U.S.C. § 102(b) ........................................................................................ 12
`35 U.S.C. § 314(a) ........................................................................................ 11
`35 U.S.C. § 316(e) ........................................................................................ 67
`35 U.S.C. § 325(d) ........................................................................................ 66
`Other Authorities
`37 C.F.R. § 42.6(e) ....................................................................................... 70
`37 C.F.R. § 42.8(b)(1) ..................................................................................... 2
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`USS. Patent 11,634,781
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`37 C.F.R. § 42.8(b)(2) ..................................................................................... 2
`37 CAFR. § 42.8(b)(2).ccssssessssssssssesssssssssssssssssvtssessssssessessssssesesssssnsesssssssnsessess 2
`37 C.F.R. § 42.8(b)(3) .................................................................................... 3
`37 CAF.R. § 42.8(b)(3) cessscssssssssssesssssssssessscssssssssccessssssscsssssusessessssssesssesssnsessees 3
`37 C.F.R § (b)(4) ............................................................................................. 3
`37 CER § (O)(4)seseccscsssssssssscsssssseesscsssssesscsssssstesscessssusecessssssessessssnssssssssnsessces 3
`37 C.F.R. § 42.10(b) ....................................................................................... 3
`37 CAFR. § 42.10(b) cesssssssssssssssssessssssssssesssssssssescessssssssssssssusessessssnsesssssssnsessees 3
`37 C.F.R. § 42.15(a) ....................................................................................... 2
`37 CFR. § 42.15(2) cecssssssssssssssssesssssssssesssssssssvessesssssssscssssssesssssssnsesssssssnsessees 2
`37 C.F.R. § 42.22(a) ....................................................................................... 4
`37 CAFR. § 42.22(a) ceessssssssscssssssesssssssssesssssssssvesscessssstsscssssssescessssnsesssssssnsessess 4
`37 C.F.R. § 42.24 .......................................................................................... 69
`37 CAR. § 42.24 vccccccccsssssesssssssssessscssssssesssessssssesssesssnsesssssssssetsesesssueusesssssseees 69
`37 C.F.R. § 42.24(a)(1) ................................................................................. 69
`37 CAFR. § 42.24(a)(1).sssccssssssssssessccsssssesscssssssvessesssssseessssssssetsesssssueeeessesssnees 69
`37 C.F.R. § 42.24(d) ..................................................................................... 69
`37 CAFR. § 42.24) cecccssssesscssssssessscsssssseescssssssvesssssssusesssssssssetsesssssseesessssssnees 69
`37 C.F.R. § 42.104(b) ................................................................................... 11
`37 CAFR. § 42.104(b) ..cscsscsssssssssessscsssssseessesssssvesssssssssesssssssnsetsesessssseessesssnees 11
`37 C.F.R. § 42.105 ........................................................................................ 70
`37 CAR. § 42.105 vceccccssssssssssssssessscssssssesssssssssvesssssssssessssssssseusessssssnesessssssnees 70
`37 C.F.R. § 42.106(a) ..................................................................................... 2
`37 CAFR. § 42.106(a) ..sccscscscssssssesssssssssessssssssssescssssssssscsssssssesssssssnsesssssssnsessees 2
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`IPR2024-00459
`U.S. Patent 11,634,781
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`EX1004 Lenhard
`
`EX1005 Vilkin
`
`EX1006
`
`Itzkowitz
`
`
`PETITIONER’S EXHIBIT LIST
`Exhibit Short Name
`Description
`EX1001
`’781 patent
`U.S. Patent No. 11,634,781.
`EX1002 Whitney
`Expert Declaration of Dr. Whitney
`Declaration
`Ph.D.
`Curriculum Vitae of Dr. Duncan
`EX1003 Whitney CV
`Whitney
`Konstanze Lenhard et al., “Analysis of
`Promoter Methylation in Stool: A
`Novel Method for the Detection of
`Colorectal Cancer,” Clinical
`Gastroenterology and Hepatology,
`3:142-149 (2005).
`Alex Vilkin et al., “Performance
`Characteristics and Evaluation of an
`Automated-Developed and
`Quantitative, Immunochemical Fecal
`Occult Blood Screening Test,”
`American Journal of Gastroenterology,
`100:2519-2525 (2005).
`Steven Itzkowitz et al., “Improved
`Fecal DNA Test for Colorectal Cancer
`Screening,” Clinical Gastroenterology
`and Hepatology, 5:111-117 (2007).
`U.S. Patent Publication Number US
`2006/0216714.
`Sarah Derks et al., “Promoter
`Methylation Precedes Chromosomal
`Alterations in Colorectal Cancer
`Development,” Cellular Oncology,
`28:247-257 (2006).
`International Patent Application
`Publication Number WO2005/113769.
`Lydia Guittet et al., “Comparison of A
`Guaiac Based And An
`Immunochemical Faecal Occult Blood
`
`EX1007 Kanaoka
`
`EX1008 Derks
`
`EX1009 Shuber
`
`EX1010 Guittet
`
`
`viii
`
`

`

`
`
`
`
`Exhibit Short Name
`
`EX1011 Nishikawa
`
`EX1012 Kutzner
`
`EX1013 Levin
`
`EX1014
`
`’581 Provisional
`Application
`’581 Transmittal
`Joost Louwagie
`Profile
`EX1017 US2016/0194723
`
`EX1015
`
`EX1016
`
`EX1018 US2012/0164238
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`Test In Screening For Colorectal
`Cancer In A General Average Risk
`Population,” Gut, 56:210-214 (2007).
`Takashi Nishikawa et al., “A Simple
`Method Of Detecting K-Ras Point
`Mutations in Stool Samples for
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`Reaction/Restriction Fragment Length
`Polymorphism Analysis,” Clinica
`Chimica Acta, 318 107–112 (2002).
`Nadie Kutzner et al., “Non-Invasive
`Detection of Colorectal Tumours by the
`Combined Application Of Molecular
`Diagnosis and the Faecal Occult Blood
`Test,” Cancer Letters, 229:33-41
`(2005).
`Bernard Levin et al., “Screening and
`Surveillance for the Early Detection of
`Colorectal Cancer and Adenomatous
`Polyps, a Joint Guideline from the
`American Cancer Society, the US
`Multi-Society Task Force on Colorectal
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`Radiology,” Gastroenterology,
`134:1570–1595 (2008).
`US Provisional Patent Application
`US61/149,581.
`Transmittal Notice for U.S. Provisional
`Patent Application US61/149,581.
`LinkedIn Page of Joost Louwagie.
`US Patent Publication No.
`US2016/0194723.
`US Patent Publication No.
`US2012/0164238.
`
`
`ix
`
`

`

`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`USPTO Final Office Action for US
`Patent Publication No. US15/010,436
`dated October 28, 2016.
`USPTO Nonfinal Office Action for US
`Patent Publication No. US17/936,335
`dated January 11, 2023.
`Request for Ex Parte Reexamination of
`US Patent No. 11,634,781 dated May
`22, 2023
`USPTO Order Granting Request for Ex
`Parte Reexamination of US Patent No.
`11,634,781 dated June 29, 2023.
`USPTO Notice of Intent to Issue Ex
`Parte Reexamination Certificate for US
`Patent No. 11, 634,781 dated Oct 18,
`2023.
`GP Young et al., “New Stool Screening
`Tests for Colorectal Cancer,”
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`Jeff Olson et al., “DNA Stabilization is
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`(1982).
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`U.S. Patent No. 5,741,650
`N. Hoepffner et al., “Comparative
`Evaluation of a New Bedside Faecal
`Occult Blood Test in a Prospective
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`
`
` x
`
`
`
`
`
`Exhibit Short Name
`
`EX1019 Final Office Action
`
`EX1021
`
`EX1022
`
`EX1020 Nonfinal Office
`Action
`Request for Ex
`Parte
`Reexamination
`Order Granting
`Request for Ex
`Parte
`Reexamination
`Notice of Intent to
`Issue Ex Parte
`Reexamination
`Certificate
`
`EX1023
`
`EX1024 Young 2007
`
`EX1025 Olson
`
`EX1026 Melvin
`
`EX1027 Lapidus ’178
`EX1028 Lapidus ’650
`
`EX1029 Hoepffner
`
`

`

`
`
`
`
`Exhibit Short Name
`
`EX1030 Nechvatal
`
`EX1031 Recorded
`Assignment
`EX1032 n/a
`
`EX1033 Simon
`
`EX1034 n/a
`
`EX1035 Sidransky
`
`EX1036 n/a
`
`EX1037 Müller
`
`EX1038 Schuebel
`
`EX1039 Shen
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`Pharmacology & Therapeutics, 23:145-
`154 (2006).
`Jordan Nechvatal et al., “Fecal
`Collection, Ambient Preservation, and
`DNA Extraction for PCR Amplification
`of Bacterial And Human Markers from
`Human Feces,” Journal of
`Microbiological Methods, 72(2):124-32
`(2008).
`Recorded Assignment of US Patent No.
`11,634,781 dated April 25, 2017.
`Intentionally Omitted
`JB Simon, “Occult Blood Screening for
`Colorectal Carcinoma: A Critical
`Review,” Gastroenterology, 88:820-
`837 (1985).
`Intentionally Omitted
`D. Sidransky, “Identification of Ras
`Oncogene Mutations in the Stool of
`Patients with Curable Colorectal
`Tumors,” Science, 256:102–105
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`Intentionally Omitted
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`Kornel Schuebel et al., “Comparing the
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`
`
`xi
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`

`

`
`
`
`
`Exhibit Short Name
`
`EX1040 Tagore
`
`EX1041 Derks Printout
`EX1042 Grow
`
`EX1043
`
`Imperiale
`
`EX1044 Ahlquist 2008
`
`EX1045 Rennert
`
`EX1046 Van Engeland
`
`EX1047 Karl
`
`EX1048 Ostrow
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`K.S. Tagore et al. “Review Article: The
`Evolution to Stool DNA Testing for
`Colorectal Cancer,” Aliment
`Pharmacol. Ther., 19: 1225-1233
`(2004).
`Printout of Clinical Oncology from
`Pubmed.
`U.S. Patent No. 5,198,365.
`Thomas Imperiale et al., “Fecal DNA
`Versus Fecal Occult Blood for
`Colorectal-Cancer Screening in an
`Average-Risk Population,” New
`England Journal of Medicine, 351(26):
`2704-2714 (2004).
`David Ahlquist et al., “Stool DNA and
`Occult Blood Testing for Screen
`Detection of Colorectal Neoplasia,”
`Annals of Internal Medicine, 149(7):
`441–W81 (2008).
`Rennert et al., “Detecting K-Ras
`Mutations in Stool from Fecal Occult
`Blood Test Cards in Multiphasic
`Screening for Colorectal Cancer,”
`Cancer Letters, 253: 258-264 (2007).
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`Publication Number WO2008/084219.
`Karl, et al., Improved Diagnosis of
`Colorectal Cancer Using a
`Combination of Fecal Occult Blood and
`Novel Fecal Protein Markers,” Clinical
`Gastroenterology and Hepatology,
`6:1122–1128 (2008).
`Donald Ostrow, “Tests for Fecal Occult
`Blood, in Clinical Methods: The
`History, Physical, and Laboratory
`Examinations.” Boston: Butterworths;
`Chapter 98 (1990).
`
`
`xii
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`

`

`
`
`
`
`Exhibit Short Name
`EX1049 Cleator
`
`EX1050 Kahi
`
`EX1051 White
`
`EX1052 Zou
`
`EX1053 Eguchi
`
`EX1054 Villa
`
`EX1055
`
`Itzkowitz 2008
`
`EX1056 Boynton
`
`EX1057
`
`Jessup
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`U.S. Patent No. 7,195,878.
`Charles Kahi et al., “Screening,
`Surveillance, and Primary Prevention
`for Colorectal Cancer: A Review of the
`Recent Literature,” Gastroenterology,
`135: 380-399 (2008).
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`“Colorectal Cancer: Prevention and
`Early Diagnosis,” Medicine, 35(6) 297-
`301 (2007).
`H Zou et al., “Highly Methylated
`Genes in Colorectal Neoplasia:
`Implications for Screening,” Cancer
`Epidemiol Biomarkers Preview,
`16(12):2686-96 (2007).
`Susumu Eguchi et al., “Mutations of
`the P53 Gene in Stool of Patients with
`Resectable Colorectal Cancer,” Cancer,
`77:1707–1710 (1996).
`E. Villa, et al., “Identification of
`Subjects at Risk for Colorectal
`Carcinoma through a Test Based on K-
`Ras Determination in the Stool,”
`Gastroenterology, 110:1346–1353
`(1996).
`Steven Itzkowtiz, “A Simplified,
`Noninvasive Stool DNA Test for
`Colorectal Cancer Detection,”
`American Journal of Gastroenterology,
`103: 2862-2870 (2008).
`Boynton et al., “DNA Integrity as a
`Potential Marker for Stool-based
`Detection of Colorectal Cancer,”
`Clinical Chemistry, 49:7 1058–1065
`(2003).
`J. Milburn Jessup et al., “Diagnosing
`Colorectal Carcinoma: Clinical and
`
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`xiii
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`
`
`
`
`Exhibit Short Name
`
`EX1058 Chen
`
`EX1059 Li
`
`EX1060
`
`Jones Declaraton
`
`EX1061 Kanaoka 2004
`
`EX1062 Matsumura 1992
`
`EX1063 Matsumura 1994
`
`EX1064 Leung
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`Molecular Approaches,” A Cancer
`Journal for Clinicians, 47(2):70-92
`(1997).
`WD Chen et al., “Detection in Fecal
`DNA of Colon Cancer-Specific
`Methylation of the Nonexpressed
`Vimentin Gene.” Journal of National
`Cancer Institute, 97:1124-1132 (2005).
`L-C Li and R. Dahiya, “MethPrimer:
`Designing Primers for Methylation
`Pcrs,” Bioinformatics, 18(11): 1427-
`1431 (2002).
`Declaration of Brendan T. Jones
`Shigeru Kanaoka et al., “Potential
`Usefulness of Detecting
`Cyclooxygenase 2 Messenger RNA in
`Feces for Colorectal Cancer
`Screening,” Gastroenterology,
`127:422-427 (2004).
`Y Matsumura and D Tarin
`“Significance of CD44 Gene Products
`for Cancer Diagnosis and Disease
`Evaluation,” Lancet, 340: 1053-1058
`(1992).
`Y Mastumura et al., “Non-Invasive
`Detection of Malignancy by
`Identification of Unusual CD44 Gene
`Activity in Exfoliated Cancer Cells,”
`BMJ, 308:619-624 (1994).
`Wai Leung et al., “Detection of
`Hypermethylated DNA or
`Cyclooxygenase-2 Messenger RNA in
`Fecal Samples of Patients with
`Colorectal Cancer or Polyps” American
`Journal Gastroenterology, 102: 1070-
`1076 (2007).
`
`
`xiv
`
`

`

`
`
`
`
`Exhibit Short Name
`
`EX1065 Ahlquist 2000
`
`EX1066 Ahlquist 2000(b)
`
`EX1067 Taylor
`
`EX1068 Mahon
`
`EX1069 Young 2004
`
`EX1070
`
`Inbar
`
`EX1071 Hirata
`
`EX1072 Ahlquist 1988
`
`EX1073 Lenhard Printout
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`D.A. Ahlquist et al., “Colorectal Cancer
`Screening by Detection of Altered
`Human DNA in Stool: Feasibility of a
`Multitarget Assay Panel,”
`Gastroenterology, 119(5):1219-1227
`(2000).
`D.A. Ahlquist et al., “Molecular Stool
`Screening for Colorectal Cancer. Using
`DNA Markers May Be Beneficial, But
`Large Scale Evaluation is Needed.”
`BMJ, 29;321(7256):254-5 (2000).
`International Patent Application
`Publication Number WO2009/102788.
`Suzanne Mahon, “ Prevention and
`Screening of Gastrointestinal Cancers,”
`Seminars in Oncology Nursing, 25(1):
`15-31 (2009).
`G.P. Young, “Fecal Immunochemical
`Tests (FIT) vs. Office-Based Guaiac
`Fecal Occult Blood Test (FOBT),”
`Practical Gastroenterology 28(6): 46-
`56 (2004).
`International Patent Application
`Publication Number WO97/25925.
`I Hirata et al., “Usefulness of Fecal
`Lactoferrin and Hemoglobin in
`Diagnosis of Colorectal Diseases,”
`World Journal of Gastroenterology,
`14;13(10):1569-74 (2007).
`D.A. Ahlquist et al., “A Stool
`Collection Device: The First Step in
`Occult Blood Testing,” Annals of
`Internal Medicine, (108)4:609-612
`(1988).
`Printout of Clinical Gastroenterology
`and Hepatology Website.
`
`
`xv
`
`

`

`
`
`
`
`
`
`Exhibit Short Name
`
`EX1074 Ahmed
`
`EX1075 Beaulieu
`Itzkowitz Printout
`EX1076
`
`Itzkowitz Press
`Release
`
`EX1077
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Description
`Farid Ahmed et al., “Transcriptomic
`Molecular Markers for Screening
`Human Colon Cancer in Stool and
`Tissue,” Cancer Genomics and
`Proteomics 4:1-20 (2007).
`U.S. Patent No. 9,891,223.
`Printout of Clinical Gastroenterology
`and Hepatology Website.
`Exact Sciences and Mount Sinai School
`of Medicine Press Release issued
`December 13, 2006.
`
`
`
`
`
`
`xvi
`
`

`

`
`
`
`
`I.
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`Introduction
`The claims of United States Patent No. 11,634,781 (“the ’781 patent”) are
`
`directed to the separation of a fecal sample into two portions to permit two
`
`standard diagnostic tests—one detecting blood proteins and the other detecting
`
`nucleic acids—to be performed on the sample. Nothing in these claims is
`
`inventive. Separating a fecal sample so it can be tested both for blood proteins and
`
`for nucleic acids is reported throughout the prior art, including in Lenhard
`
`(EX1004). The fecal tests for detecting blood protein and nucleic acids recited by
`
`the claims were known and routine, as confirmed by Vilkin (EX1005), Itzkowitz
`
`(EX1006), and Shuber (EX1009). The method claimed by the ’781 patent amounts
`
`to no more than the routine use of conventional methods to prepare a fecal sample
`
`for performance of well-established complementary diagnostic assays. The claimed
`
`method is obvious, and the claims directed to the method are invalid.
`
`The Board should institute IPR based on Lenhard, Itzkowitz, Vilkin, Shuber,
`
`and the other references cited in the grounds herein and should cancel claims 1-20
`
`of the ’781 patent.
`
`The Petitioner, Geneoscopy, Inc. (“Geneoscopy”) is a life sciences company
`
`focused on transforming gastrointestinal health through innovative diagnostics,
`
`including through its work to develop a noninvasive, at-home screening test for
`
`colorectal cancer. With the goal of expanding cancer detection options and
`
`
`
` 1
`
`

`

`
`
`
`improving outcomes for millions of at-risk patients, Geneoscopy has an interest in
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`ensuring that the Patent Owner does not foreclose innovation and advancement in
`
`the field of cancer detection by claiming exclusive rights to diagnostic methods it
`
`did not invent.
`
`II. STANDING AND PROCEDURAL STATEMENTS
`Geneoscopy certifies: (1) the ’781 patent is available for IPR; and (2)
`
`Petitioner is not barred or estopped from requesting IPR of any ’781 patent claim
`
`on the grounds identified herein. This Petition is filed in accordance with 37 C.F.R.
`
`§ 42.106(a). Geneoscopy is submitting a Power of Attorney and an Exhibit List
`
`pursuant to § 42.10(b) and § 42.63(e), and all required fees pursuant to 37 C.F.R.
`
`§ 42.15(a), concurrently with this Petition. If any additional fees are due at any
`
`time during this proceeding, the Office is authorized to charge such fees to Deposit
`
`Acct. No. 06-1448.
`
`III. MANDATORY NOTICES & PROCEDURAL STATEMENTS
`A. Real Party-in-Interest, 37 C.F.R. § 42.8(b)(1)
`The real party-in-interest is Geneoscopy, Inc., which is located at 2220
`
`Welsch Industrial Court, St. Louis, MO 63146.
`
`B. Related Matters, 37 C.F.R. § 42.8(b)(2)
`The Patent Owner, Exact Sciences, Inc. (“Exact”) has asserted the ’781
`
`patent against Geneoscopy in Exact Sciences Corporation v. Geneoscopy, Inc., No.
`
`
`
` 2
`
`

`

`
`
`
`23-cv-1319-MN (D. Del.) (“the Exact Litigation”). Geneoscopy was served with
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`the complaint in the Exact Litigation on November 17, 2023.
`
`C. Lead and Backup Counsel and Service Information, 37 C.F.R. §
`42.8(b)(3) and (b)(4)
`Petitioner provides the following designation of counsel for which a power
`
`of attorney is being filed contemporaneously. 37 C.F.R. § 42.10(b).
`
`Backup Counsel
`David Shore (Reg. No. 75,183)
`Foley Hoag LLP
`155 Seaport Boulevard
`Boston, MA 02210-2600
`T: (617) 832-1714
`F: (617) 832-7000
`dshore@foleyhoag.com
`Donald R. Ware
`(pro hac vice admission to be
`requested)
`Foley Hoag LLP
`155 Seaport Boulevard
`Boston, MA 02210-2600
`T: (617) 832-1714
`F: (617) 832-7000
`dware@foleyhoag.com
`Sarah Burg
`(pro hac vice admission to be
`requested)
`Foley Hoag LLP
`155 Seaport Boulevard
`Boston, MA 02210-2600
`T: (617) 832-1249
`F: (617) 832-7000
`sburg@foleyhoag.com
`
`
`
` 3
`
`Lead Counsel
`Brendan Jones (Reg. No. 65,077)
`Foley Hoag LLP
`155 Seaport Boulevard
`Boston, MA 02210-2600
`T: (617) 832-1267
`F: (617) 832-7000
`bjones@foleyhoag.com
`
`
`
`
`
`
`
`

`

`
`
`
`
`Petitioner consents to service by email at bjones@foleyhoag.com,
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`dshore@foleyhoag.com, dware@foleyhoag.com, sburg@foleyhoag.com, and
`
`geneoscopyIPR@foleyhoag.com.
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR, 37 C.F.R. § 42.22(a)
`Geneoscopy requests institution of IPR and cancellation of claims 1-20 of
`
`the ’781 patent, for the reasons stated herein.
`
`V. BACKGROUND
`A. Technical Background
`1.
`Sample Collection and Preparation
`By February 3, 2009 (the earliest priority date asserted by the ’781 patent;
`
`“the Priority Date”), fecal samples had been used in non-invasive diagnostic tests
`
`for colorectal cancer (CRC) for decades. EX1002 ¶¶49-59. Such tests generally
`
`involved obtaining a stool sample from a patient and testing it for one or more
`
`biomarkers associated with CRC. EX1002 ¶¶49, 60-65. The CRC biomarkers
`
`known to be present in feces included blood proteins, mutated DNA, long DNA
`
`fragments, hypermethylated DNA, and RNA. EX1002 ¶¶49-59. It was broadly
`
`recognized that increasing the number of biomarkers used in such a diagnostic test
`
`could improve the test’s sensitivity and/or specificity. EX1002 ¶¶30-33, 60-65.
`
`Many fecal diagnostic assays require specialized equipment and/or expertise,
`
`and accordingly are usually performed in medical diagnostics laboratories.
`
`
`
` 4
`
`

`

`
`
`
`EX1002 ¶66. For such assays, patients typically collect their own stool sample at
`
`IPR2024-00459
`U.S. Patent 11,634,781
`
`home using a specially-designed kit and then ship it to the laboratory for testing.
`
`EX1002 ¶¶66-72. To eliminate the need to freeze samples during shipment,
`
`scientists developed buffers that stabilize components of the fecal sample. EX1002
`
`¶¶73-81. For example, certain buffers prevent degradation of DNA, and are
`
`employed when DNA biomarkers are used. EX1002 ¶¶74-77. Other buffers
`
`stabilize proteins and are used when blood proteins are used as biomarkers.
`
`EX1002 ¶¶78-80.
`
`Decades before the Priority Date, scientists and clinicians recognized that
`
`testing different biomarkers could be facilitated by instructing patients to separate
`
`their fecal sample into portions stabilized in separate containers prior to shipment
`