`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`GENEOSCOPY, INC.,
`Petitioner,
`
`v.
`
`EXACT SCIENCES CORPORATION,
`Patent Owner.
`____________
`
`Case No.: IPR2024-01330
`U.S. Patent 11,970,746
`____________
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT 11,970,746
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`V.
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`TABLE OF CONTENTS
`Introduction .......................................................................................... 1
`I.
`STANDING AND PROCEDURAL STATEMENTS ......................... 3
`II.
`III. MANDATORY NOTICES & PROCEDURAL STATEMENTS ....... 3
`A.
`Real Party-in-Interest, 37 C.F.R. § 42.8(b)(1) ........................... 3
`B.
`Related Matters, 37 C.F.R. § 42.8(b)(2) .................................... 3
`C.
`Lead and Backup Counsel and Service Information, 37
`C.F.R. § 42.8(b)(3) and (b)(4) .................................................... 4
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`THE REASONS THEREFOR ............................................................. 5
`BACKGROUND .................................................................................. 5
`A.
`Technical Background ............................................................... 5
`1.
`Sample Collection and Preparation ................................. 5
`2.
`Fecal Occult Blood Tests ................................................. 8
`3.
`Fecal Nucleic Acid Tests ................................................. 8
`The ’746 Patent ........................................................................ 10
`B.
`IDENTIFICATION OF THE CHALLENGE .................................... 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) ....................................................... 15
`4.
`Kanaoka (EX1007) ........................................................ 16
`5.
`Shuber (EX1008) ........................................................... 16
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`VI.
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`U.S. Patent 11,970,746
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`4.
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`Inbar (EX1009) .............................................................. 17
`6.
`VII. DETAILED EXPLANATION OF THE GROUNDS ........................ 19
`A. Ground I: Lenhard in view of Itzkowitz and Vilkin ................ 19
`1.
`Claim 1 ........................................................................... 24
`2.
`Claim 2: “The method of claim 1, further comprising
`delivering the sealable vessel… and the sealable
`container… to a medical diagnostics laboratory” .......... 28
`Claim 3 ........................................................................... 28
`Claim 4: “The method of claim 3, wherein testing the
`nucleic acid comprises determining expression from
`a human gene.” .............................................................. 31
`Claim 14: “The method of claim 3, wherein testing
`for an amount of blood protein present in the second
`portion comprises testing for a concentration of
`hemoglobin in the second portion, wherein a
`concentration of hemoglobin is indicative of a
`presence of blood in the fecal sample.”
`Claim 15: “The method of claim 14, wherein the
`testing for the concentration of hemoglobin
`comprises immunochemical detection of
`hemoglobin.” .................................................................. 32
`Claims 16-19: “The method of claim 14, wherein the
`second portion of the fecal sample is considered
`positive for the presence of blood when the
`concentration of hemoglobin detected in the second
`portion is at least [5, 10, 20, or 50] ng/ml.” ................... 33
`B. Ground II: Lenhard in view of Itzkowitz and Vilkin, in
`further view of Kanaoka ........................................................... 35
`1.
`Claim 12: “The method of claim 4, wherein
`determining expression from the human gene
`comprises measuring an amount of RNA expressed
`from the human gene.” ................................................... 35
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`5.
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`6.
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`2.
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`U.S. Patent 11,970,746
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`3.
`4.
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`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)” ............................................. 37
`C. Ground III: Shuber and Vilkin ................................................. 37
`1.
`Claim 1 ........................................................................... 41
`2.
`Claim 2: “The method of claim 1, further comprising
`delivering the sealable vessel… and the sealable
`container… to a medical diagnostics laboratory” .......... 44
`Claim 3 ........................................................................... 44
`Claim 4: “The method of claim 3, wherein testing the
`nucleic acid comprises determining expression from
`a human gene.” .............................................................. 46
`Claim 14: “The method of claim 3, wherein testing
`for an amount of blood protein present in the second
`portion comprises testing for a concentration of
`hemoglobin in the second portion, wherein a
`concentration of hemoglobin is indicative of a
`presence of blood in the fecal sample.”
`Claim 15: “The method of claim 14, wherein the
`testing for the concentration of hemoglobin
`comprises immunochemical detection of
`hemoglobin.” .................................................................. 47
`Claims 16-19: “The method of claim 14, wherein the
`second portion of the fecal sample is considered
`positive for the presence of blood when the
`concentration of hemoglobin detected in the second
`portion is at least [5, 10, 20, or 50] ng/ml.” ................... 47
`D. Ground IV: Shuber and Vilkin, in further view of Kanaoka ... 48
`1.
`Claims 12 “The method of claim 4, wherein
`determining expression from the human gene
`comprises measuring an amount of RNA expressed
`from the human gene.” ................................................... 48
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`5.
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`6.
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`2.
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`E.
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`F.
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`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)” ............................................. 49
`Ground V: Inbar ....................................................................... 49
`1.
`Claim 1 ........................................................................... 53
`2.
`Claim 2: “The method of claim 1, further comprising
`delivering the sealable vessel… and the sealable
`container… to a medical diagnostics laboratory” .......... 56
`Ground VI: Inbar, Shuber, and Vilkin ..................................... 56
`1.
`Claim 1 ........................................................................... 58
`2.
`Claim 2: “The method of claim 1, further comprising
`delivering the sealable vessel… and the sealable
`container… to a medical diagnostics laboratory” .......... 60
`Claim 3 ........................................................................... 61
`Claim 4: “The method of claim 3, wherein testing the
`nucleic acid comprises determining expression from
`a human gene.” .............................................................. 63
`Claim 14: “The method of claim 3, wherein testing
`for an amount of blood protein present in the second
`portion comprises testing for a concentration of
`hemoglobin in the second portion, wherein a
`concentration of hemoglobin is indicative of a
`presence ofblood in the fecal sample.” .......................... 63
`Claim 15: “The method of claim 14, wherein the testing for
`the concentration of hemoglobin comprises
`immunochemical detection of hemoglobin.” ................. 64
`Claims 16-19: “The method of claim 14, wherein the
`second portion of the fecal sample is considered
`positive for the presence of blood when the
`concentration of hemoglobin detected in the second
`portion is at least [5, 10, 20, or 50] ng/ml.” ................... 64
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`3.
`4.
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`5.
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`6.
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`2.
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`G. Ground VII: Inbar, Shuber and Vilkin, in further view of
`Kanaoka .................................................................................... 65
`1.
`Claim 12 “The method of claim 4, wherein
`determining expression from the human gene
`comprises measuring an amount of RNA expressed
`from the human gene.” ................................................... 65
`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)” ............................................. 65
`VIII. Secondary Considerations of Non-obviousness ................................. 66
`IX. Discretion under 35 U.S.C. § 325(d) .................................................. 69
`X.
`Conclusion .......................................................................................... 71
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`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) .......................... 69, 71
`Alcon Research, LTD. v. Apotex Inc.,
`687 F.3d 1362 (Fed. Cir. 2012) ............................................................... 31
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) ................................................... 33, 48, 64
`Exact Sciences Corporation v. Geneoscopy, Inc.,
`No. 23-cv-1319-MN (D. Del.) ................................................................... 3
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007)................................................................................. 26
`Satco Products Inc. v. The Regents of the Univ. of California,
`IPR2021-00662, Paper 13 (P.T.A.B. Nov. 8, 2021) ................................ 70
`ZUP, LLC v. Nash Mfg., Inc.,
`896 F.3d 1365 (Fed. Cir. 2018) ............................................................... 66
`Statutes
`35 U.S.C. § 102(b) ........................................................................................ 12
`35 U.S.C. § 316(e) ........................................................................................ 71
`35 U.S.C. § 325(d) ........................................................................................ 69
`Other Authorities
`37 C.F.R. § 42.6(e) ....................................................................................... 74
`37 C.F.R. § 42.8(b)(1) ..................................................................................... 3
`37 C.F.R. § 42.8(b)(2) ..................................................................................... 3
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`37 C.F.R. § 42.8(b)(3) .................................................................................... 4
`37 CAF.R. § 42.8(D)(3) cccecscsssessssssssccssscscsssusscssnsccessusscersuescssnstecssuseesssnesessneeseen 4
`37 C.F.R. § 42.10(b) ....................................................................................... 4
`37 CER. § 42.10(b) cccccccsscsssessssssssccsssescessusscssusccessssscersusscssnsecssuseesssutsessneeeeen 4
`37 C.F.R. § 42.15(a) ....................................................................................... 3
`37 CFR. § 42.15(a) cccccscsscsssessssssesccssscscessussssssseecsssessersuesesssseecsssseesssnesessneeeeen 3
`37 C.F.R. § 42.24 .......................................................................................... 73
`37 CAFR. § 42.24 vvccccscsssssscsssesscsssesssssussesssusecsssseccsssecsessutsesssuecsrsssesssneessaseees 73
`37 C.F.R. § 42.24(a)(1) ................................................................................. 73
`37 CLF. § 42.24(a)(1) scccsccscsescsssecscssseccersucscesssecsssssessssstsessssecssseseessnseesssseees 73
`37 C.F.R. § 42.24(d) ..................................................................................... 73
`37 CER. § 42.24(d) cceccscsscsssesscsssesscssssscsssucscesssecesssesesssusesssssecsssetsessneesssseees 73
`37 C.F.R. § 42.105 ........................................................................................ 74
`37 CAFR. § 42.105 vcccccccscsccssesscsssescsssssscsssucscesssecesssessessuesessssecsssesesssneeessaseees 74
`37 C.F.R. § 42.106(a) ..................................................................................... 3
`37 CAE.R. § 42.106(a) ceccecsccsscscsssssccsssescsssusscssssccessueccersuesessnsesessuseesssuseessseeeeen 3
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`U.S. Patent 11,970,746
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`PETITIONER’S EXHIBIT LIST
`
`Exhibit
`Short Name
`No.
`’746 patent
`EX1001
`EX1002 Whitney
`Declaration
`EX1003 Whitney CV
`
`EX1004
`
`Lenhard
`
`EX1005
`
`Vilkin
`
`EX1006
`
`Itzkowitz
`
`EX1007
`
`Kanaoka
`
`EX1008
`
`Shuber
`
`EX1009
`
`Inbar
`
`EX1010 Melvin
`
`Description
`U.S. Patent No. 11,970,746.
`Expert Declaration of Dr. Whitney Ph.D.
`Curriculum Vitae of Dr. Duncan 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.
`International Patent Application Publication
`Number WO2005/113769.
`International Patent Application Publication
`Number WO97/25925.
`Dorothy Melvin and Marion Brooke,
`“Laboratory Procedures for the Diagnosis of
`Intestinal Parasites”, U.S. Department of
`Health and Human Services Centers for
`Disease Control (1982).
`
`
`viii
`
`
`
`
`
`
`
`EX1011
`
`Nishikawa
`
`EX1012
`
`Kutzner
`
`EX1013
`
`Levin
`
`EX1014
`
`EX1015
`
`EX1016
`
`EX1017
`
`EX1018
`
`EX1019
`
`’581
`Provisional
`Application
`’581
`Transmittal
`Joost Louwagie
`Profile
`Recorded
`Assignment
`Nonfinal Office
`Action
`Response to
`Nonfinal Office
`Action
`
`EX1020
`
`Young 2007
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`Takashi Nishikawa et al., “A Simple
`Method of Detecting K-Ras Point Mutations
`in Stool Samples for Colorectal Cancer
`Screening Using One-Step Polymerase
`Chain 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 Cancer, and the
`American College of 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.
`Recorded Assignment of OncoMethylome
`patent family dated April 25, 2017.
`Nonfinal Office Action of July 6, 2023
`issued during prosecution of '746 patent
`Response to Nonfinal Office Action filed on
`October 26, 2023 during prosecution of '746
`patent
`GP Young et al., “New Stool Screening
`Tests for Colorectal Cancer,” Digestion,
`76:26-33 (2007).
`
`
`ix
`
`
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`Lydia Guittet et al., “Comparison of A
`Guaiac Based and An Immunochemical
`Faecal Occult Blood Test in Screening for
`Colorectal Cancer In A General Average
`Risk Population,” Gut, 56:210-214 (2007).
`Jeff Olson et al., “DNA Stabilization is
`Critical for Maximizing Performance of
`Fecal DNA-Based Colorectal Cancer Tests,”
`Diagnostic Molecular Pathology, 3:183-191
`(2005).
`N. Hoepffner et al., “Comparative
`Evaluation of a New Bedside Faecal Occult
`Blood Test in a Prospective Multicentre
`Study,” Alimentary 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).
`"FDA Approves Exact Sciences' Cologuard;
`First and Only Stool DNA Noninvasive
`Colorectal Cancer Screening Test" PR
`Newswire Association LLC, August 12,
`2014
`Printout of Exact Sciences' "Patents and
`Trademarks" page from their website, as
`visited on August 9, 2024.
`Printout of Exact Sciences' "Patents and
`Trademarks" page from their website as of
`December 6, 2104. Downloaded from
`Wayback Machine on August 9, 2024.
`U.S. Patent No. 9,163,278
`Response to Nonfinal Office Action filed on
`July 31, 2015 during prosecution of '278
`patent
`U.S. Patent No. 11,634,781.
`
`
`
` x
`
`
`
`
`
`EX1021
`
`Guittet
`
`EX1022
`
`Olson
`
`EX1023
`
`Hoepffner
`
`EX1024
`
`Nechvatal
`
`EX1025
`
`EX1026
`
`EX1027
`
`EX1028
`
`EX1029
`
`EX1030
`
`Cologuard
`Launch Press
`Release`
`
`Cologuard
`Patent
`Coverage, 2024
`Cologuard
`Patent
`Coverage, 2014
`’278 patent
`’278 patent
`Office Action
`Response
`’781 patent
`
`
`
`
`
`
`
`EX1031
`
`EX1032
`
`EX1033
`
`IPR2024-00459
`Petition
`IPR2024-00459
`POPR
`IPR2024-00459
`Institution
`Decision
`
`EX1034
`
`Simon
`
`EX1035
`
`Sidransky
`
`EX1036 Müller
`
`EX1037
`
`Schuebel
`
`EX1038
`
`Shen
`
`EX1039
`
`Tagore
`
`EX1040
`
`Rennert
`
`EX1041
`
`Grow
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`IPR2024-00459 Petition
`IPR2024-00459 Patent Owner's Preliminary
`Response
`
`IPR2024-00459 Institution Decision
`
`JB Simon, “Occult Blood Screening for
`Colorectal Carcinoma: A Critical Review,”
`Gastroenterology, 88:820-837 (1985).
`D. Sidransky, “Identification of Ras
`Oncogene Mutations in the Stool of Patients
`with Curable Colorectal Tumors,” Science,
`256:102–105 (1992).
`Hannes Müller et al., “Methylation Changes
`in Faecal DNA: A Marker for Colorectal
`Cancer Screening?” Lancet, 63:1283-1285
`(2004).
`Kornel Schuebel et al., “Comparing the
`DNA Hypermethylome with Gene
`Mutations in Human Colorectal Cancer,”
`PLoS Genet., 3:1709–1723 (2007).
`Lanlan Shen et al., “Integrated Genetic and
`Epigenetic Analysis Identifies Three
`Different Subclasses of Colon Cancer.”
`Proc Natl. Acad. Sci. U.S.A., 104(47):
`18654–18659 (2007).
`K.S. Tagore et al. “Review Article: The
`Evolution to Stool DNA Testing for
`Colorectal Cancer,” Aliment Pharmacol.
`Ther., 19: 1225-1233 (2004).
`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).
`U.S. Patent No. 5,198,365.
`
`
`xi
`
`
`
`
`
`
`
`EX1042
`
`Imperiale 2004
`
`EX1043
`
`Ahlquist 2008
`
`EX1044
`
`Young 2004
`
`EX1045
`
`Karl
`
`EX1046 White
`
`EX1047 Mahon
`
`EX1048
`
`Beaulieu
`
`EX1049
`
`Ostrow
`
`EX1050
`
`Cleator
`
`EX1051
`
`Kahi
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`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).
`G.P. Young, “Fecal Immunochemical Tests
`(FIT) vs. Office-Based Guaiac Fecal Occult
`Blood Test (FOBT),” Practical
`Gastroenterology 28(6): 46-56 (2004).
`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).
`Victoria White and Richard Miller,
`“Colorectal Cancer: Prevention and Early
`Diagnosis,” Medicine, 35(6) 297-301
`(2007).
`Suzanne Mahon, “ Prevention and
`Screening of Gastrointestinal Cancers,”
`Seminars in Oncology Nursing, 25(1): 15-31
`(2009).
`U.S. Patent No. 9,891,223.
`Donald Ostrow, “Tests for Fecal Occult
`Blood, in Clinical Methods: The History,
`Physical, and Laboratory Examinations.”
`Boston: Butterworths; Chapter 98 (1990).
`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).
`
`
`xii
`
`
`
`
`
`
`
`EX1052
`
`Zou
`
`EX1053
`
`Eguchi
`
`EX1054
`
`Villa
`
`EX1055
`
`Boynton
`
`EX1056
`
`Jessup
`
`EX1057
`
`Chen
`
`EX1058
`
`Itzkowitz 2008
`
`EX1059
`
`Li
`
`EX1060
`
`Kanaoka 2004
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`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).
`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
`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).
`Steven Itzkowtiz, “A Simplified,
`Noninvasive Stool DNA Test for Colorectal
`Cancer Detection,” American Journal of
`Gastroenterology, 103: 2862-2870 (2008).
`L-C Li and R. Dahiya, “MethPrimer:
`Designing Primers for Methylation Pcrs,”
`Bioinformatics, 18(11): 1427-1431 (2002).
`Shigeru Kanaoka et al., “Potential
`Usefulness of Detecting Cyclooxygenase 2
`Messenger RNA in Feces for Colorectal
`Cancer Screening,” Gastroenterology,
`127:422-427 (2004).
`
`
`xiii
`
`
`
`
`
`
`
`EX1061 Matsumura
`1992
`
`EX1062 Matsumura
`1994
`
`EX1063
`
`Leung
`
`EX1064
`
`Ahmed
`
`EX1065
`
`Ahlquist 2000
`
`EX1066
`
`Ahlquist
`2000(b)
`
`EX1067
`EX1068
`EX1069
`
`Taylor
`Lapidus ’650
`Lapidus ’178
`
`EX1070
`
`Hirata
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`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).
`Farid Ahmed et al., “Transcriptomic
`Molecular Markers for Screening Human
`Colon Cancer in Stool and Tissue,” Cancer
`Genomics and Proteomics 4:1-20 (2007).
`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.
`U.S. Patent No. 5,741,650
`U.S. Patent No. 5,952,178
`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).
`
`
`xiv
`
`
`
`
`
`
`
`EX1071
`
`Ahlquist 1988
`
`EX1072
`
`EX1073
`
`EX1074
`
`EX1075
`
`EX1076
`
`Lenhard
`Printout
`Van Engeland
`Itzkowitz
`Printout
`Itzkowitz Press
`Release
`Cologuard
`Patient Guide
`
`EX1077
`
`Imperiale 2014
`
`EX1078
`
`EX1079
`
`EX1080
`
`EX1081
`
`EX1082
`
`EX1083
`
`Exact Sciences
`2023 Form 10-
`K
`Exact Sciences
`Cologuard web
`page
`Cologuard
`Physician
`Brochure
`Cologuard
`Instructions for
`Use
`Whitney
`Declaration in
`IPR2024-00459
`Jones
`Declaration
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`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.
`International Patent Application Publication
`Number WO2008/084219.
`Printout of Clinical Gastroenterology and
`Hepatology Website.
`Exact Sciences and Mount Sinai School of
`Medicine Press Release issued December
`13, 2006.
`Cologuard Patient Guide as approved by the
`Food and Drug Administration
`Imperiale, et al., “Multitarget Stool DNA
`Testing for Colorectal-Cancer Screening,”
`The New England Journal of Medicine,
`370(14):1287-1297 (2014)
`Exact Sciences Corporation’s 2023 Form
`10-K.
`Exact Science’s webpage regarding the
`Cologuard test as obtained from
`https://www.exactsciences.com/our-
`tests/cologuard on August 15, 2024.
`Cologuard Physician Brochure as approved
`by the Food and Drug Administration
`Cologuard sDNA-based Colorectal Cancer
`Screening Test Instructions for Use as
`approved by the Food and Drug
`Administration
`Duncan Whitney Ph.D.’s Declaration
`submitted in IPR2024-00459
`
`Declaration of Brendan T. Jones
`
`
`
`xv
`
`
`
`
`
`
`
`I.
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`Introduction
`The claims of United States Patent No. 11,970,746 (“the ’746 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 two tests can be performed is reported
`
`throughout the prior art, including in Lenhard (EX1004) and Inbar (EX1009).
`
`Fecal tests for detecting blood protein and nucleic acids were known and routine,
`
`as confirmed by Lenhard, Inbar, Vilkin (EX1005), Itzkowitz (EX1006), and
`
`Shuber (EX1008). The method claimed by the ’746 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 not new, and claims directed to the method are invalid.
`
`In IPR2024-00459, Petitioner challenged the claims of United States Patent
`
`No. 11,634,781 (“the ’781 patent), the parent of the ’746 patent, as obvious in view
`
`of Lenhard, Itzkowitz, Vilkin, and Shuber, essentially for the reasons set forth in
`
`Grounds I-IV of this petition. EX1031. The Board instituted IPR2024-00459,
`
`finding there was “a reasonable likelihood … that the challenged claims would
`
`have been unpatentable as obvious” over the same prior art asserted in Grounds I-
`
`IV of this petition. EX1033 at 19, 20. As explained below, the scope of the
`
`
`
` 1
`
`
`
`
`
`
`currently challenged claims is broader than, and completely encompasses, that of
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`the corresponding claims of the ’781 patent. Accordingly, the Board’s holdings in
`
`its IPR2024-00459 institution decision concerning the obviousness of the ’781
`
`claims applies equally to the currently challenged claims. EX1030; EX1001;
`
`EX1002 ¶¶107-111.
`
`An additional consequence of expanding the scope of the ’746 patent’s
`
`claims is that some of the claims now read on Inbar, a decades-old patent
`
`application that Petitioner did not assert in IPR2024-00459, but that anticipates the
`
`broader claims 1 and 2 of the ’746 patent.
`
`The Board should institute IPR based on Lenhard, Itzkowitz, Vilkin, Shuber,
`
`Inbar, and the other references cited in the grounds herein and should cancel claims
`
`1-4 and 12-19 of the ’746 patent.
`
`The Petitioner, Geneoscopy, Inc. (“Geneoscopy”) is a life sciences company
`
`focused on transforming gastrointestinal health through innovative diagnostics,
`
`including through its work developing a noninvasive, at-home screening test for
`
`colorectal cancer (CRC). Geneoscopy has an interest in 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.
`
`
`
` 2
`
`
`
`
`
`
`
`II. STANDING AND PROCEDURAL STATEMENTS
`Geneoscopy certifies: (1) the ’746 patent is available for IPR; and (2)
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`Petitioner is not barred or estopped from requesting IPR of any ’746 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”) asserted the ’746 patent
`
`against Geneoscopy in Exact Sciences Corporation v. Geneoscopy, Inc., No. 24-
`
`cv-00583-MN (D. Del.). Geneoscopy was served with the complaint in this
`
`litigation on May 16, 2024. On June 18, 2024, this matter was consolidated with
`
`Exact Sciences Corporation v. Geneoscopy, Inc., No. 23-cv-1319-MN (D. Del.)
`
`(“the Exact Litigation”), which is currently pending.
`
`
`
` 3
`
`
`
`
`
`
`
`Geneoscopy filed a Petition for Inter Partes Review of the ’781 patent on
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`January 11, 2024 in Case No. IPR2024-00459. The ’781 patent is the parent of the
`
`’746 patent. The Board instituted IPR2024-00459 on July 26, 2024.
`
`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
`
`
`
` 4
`
`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
`
`
`
`
`
`
`
`
`
`
`
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`Petitioner consents to service by email at bjones@foleyhoag.com,
`
`dshore@foleyhoag.com, dware@foleyhoag.com, sburg@foleyhoag.com, and
`
`geneoscopyIPR@foleyhoag.com.
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR
`Geneoscopy requests institution of IPR and cancellation of claims 1-4 and
`
`12-19 of the ’746 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 ’746 patent;
`
`“the Priority Date”), fecal samples had been used in non-invasive diagnostic tests
`
`for CRC for decades. EX1002 ¶¶17-27, 50-60. Such tests generally involved
`
`obtaining a stool sample from a patient and testing it for one or more biomarkers
`
`associated with CRC. EX1002 ¶¶50-66. The CRC biomarkers known to be present
`
`in feces included blood proteins, mutated DNA, long DNA fragments,
`
`hypermethylated DNA, and RNA. Id. It was broadly recognized that increasing the
`
`number of biomarkers used in such a test could improve its sensitivity and/or
`
`specificity. EX1002 ¶¶28-34, 61-66.
`
`
`
` 5
`
`
`
`
`
`
`
`Many fecal diagnostic assays require specialized equipment and/or expertise,
`
`IPR2024-01330
`U.S. Patent 11,970,746
`
`and accordingly are usually performed in diagnostics laboratories. EX1002 ¶67.
`
`For such assays, patien
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