UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________
`
`HOLOGIC, INC.,
`Petitioner
`
`v.
`
`ENZO LIFE SCIENCES, INC.
`Patent Owner
`
`____________
`
`U.S. Patent No. 7,064,197
`
`SYSTEM, ARRAY AND NON-POROUS SOLID SUPPORT
`COMPRISING FIXED OR IMMOBILIZED NUCLEIC ACIDS
`____________
`
`PETITION FOR INTER PARTES REVIEW
`
`
`
`
`
`

`
`
`
`I.
`
`
`TABLE OF CONTENTS
`Introduction ...................................................................................................... 1
`
`II. Grounds for Standing ....................................................................................... 1
`
`III. Mandatory Notices Under 37 C.F.R. § 42.8(b) ............................................... 2
`
`A.
`
`B.
`
`Real Party–In–Interest ........................................................................... 2
`
`Related Matters ...................................................................................... 2
`
`IV. Lead and Back-up Counsel; Electronic Service .............................................. 3
`
`V.
`
`Fee Payment ..................................................................................................... 3
`
`VI. Statement of Precise Relief Requested ............................................................ 4
`
`A.
`
`B.
`
`C.
`
`Claims for Which Review is Requested ................................................ 4
`
`Statutory Grounds of Challenge ............................................................ 4
`
`Level of Ordinary Skill in the Art at the Time of the Claimed
`Invention ................................................................................................ 7
`
`VII. Prosecution History of the ’197 Patent and the State of the Art ..................... 8
`
`A. Hybridizable Nucleic Acids Bound to Solid Supports .......................... 8
`
`B.
`
`C.
`
`Summary of Prosecution History .......................................................... 9
`
`Specification of the ’197 Patent ..........................................................10
`
`VIII. Claim Construction ........................................................................................12
`
`A.
`
`B.
`
`“Non-Porous Solid Support” ...............................................................12
`
`“Hybridizable form” ............................................................................14
`
`IX. The Challenged Claims of the ’197 Patent Are Unpatentable ......................15
`
`A. Ground 1: Claims 1, 6, 8, 9, 12, 13, 14, 15, 16, 27, 31, 32, 33,
`34, 41, 61, 62, 63, 68, 69, 70, 72, 73, 74, 79, 100, 191, 192,
`
`i
`
`

`
`193, 194, 212, 213, 219, 222, 225, 226, 227, 230, 233, and 236
`are anticipated by Fish. ........................................................................15
`
`1.
`
`Independent claims 1, 6, 8, 9, 12, 13, 14, 15, and 27 ...............17
`
`a.
`
`b.
`
`c.
`
`“A non-porous solid support,” “[a] system
`comprising a non-porous solid support,” or “[a]
`non-porous glass or a non-porous plastic solid
`support.” ..........................................................................18
`
`“one or more amine(s), hydroxyl(s) or epoxide(s)
`thereon” ...........................................................................20
`
`“single stranded nucleic acid”/ “nucleic acid”/
`“DNA or RNA”“is fixed or immobilized in
`hybridizable form to said non-porous solid support
`via said one or more amine(s), hydroxyl(s) or
`epoxide(s)” ......................................................................21
`
`2.
`
`Dependent claims 16, 31, 32, 33, 34, 41, 61, 62, 63, 68,
`69, 70, 72, 73, 74, 79, 100, 191, 192, 193, 194, 212, 213,
`219, 222, 225, 226, 227, 230, 233, and 236. .............................30
`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`f.
`
`g.
`
`h.
`
`i.
`
`Claims 16, 222, and 230 .................................................30
`
`Claims 32, 72, 226, and 227 ...........................................30
`
`Claims 33, 41, 73, 212, 225, and 233 .............................30
`
`Claims 34, 74, and 213 ...................................................31
`
`Claims 31, 68, and 192 ...................................................31
`
`Claim 61, 100, and 191 ...................................................32
`
`Claims 62, 69, and 193 ...................................................32
`
`Claims 63, 70, and 194 ...................................................32
`
`Claims 79, 219, and 236 .................................................33
`
`B. Ground 2: Claims 31, 64, 68, 101, 192, and 195 are obvious
`under 35 U.S.C. § 103(a) in view of Fish ...........................................33
`
`ii
`
`

`
`a.
`
`b.
`
`Claims 31, 68, and 192 ...................................................35
`
`Claims 64, 101, and 195 .................................................37
`
`C. Ground 3: Claims 38, 78, and 218 would have been obvious
`under 35 U.S.C. § 103(a) based on Fish in view of Gilham. ..............37
`
`D. Ground 4: Claims 1, 6, 8, 9, 12, 13, 14, 15, 27, 31, 32, 34, 61,
`62, 63, 68, 69, 70, 72, 74, 79, 100, 191, 192, 193, 194, 213,
`219, 226, 227, and 236 are anticipated under 35 U.S.C. § 102(b)
`by VPK. ...............................................................................................39
`
`1.
`
`The Challenged Claims Are Entitled to a Priority Date
`No Earlier Than the Filing of the CIP Application (Appl.
`No. 06/732,374) ........................................................................40
`
`a.
`
`b.
`
`The legal requirements for claiming priority..................41
`
`The original disclosure of the 1983 application
`does not provide written description support for
`the element “non-porous solid support.” ........................42
`
`2.
`
`Claims 1, 6, 8, 9, 12, 13, 14, 15, 27, 31, 32, 34, 61, 62,
`63, 68, 69, 70, 72, 74, 79, 100, 191, 192, 193, 194, 213,
`219, 226, 227, and 236 are anticipated by VPK. ......................45
`
`a.
`
`b.
`
`Independent claims 1, 6, 8, 9, 12, 13, 14, 15, and
`27 ....................................................................................45
`
`Dependent claims 31, 32, 34, 61, 62, 63, 68, 69,
`70, 72, 74, 79, 100, 191, 192, 193, 194, 213, 219,
`226, 227, and 236 are anticipated by VPK. ....................49
`
`E.
`
`F.
`
`Ground 5: Claims 16, 38, 64, 78, 101, 195, 218, 222, and 230
`would have been obvious under 35 U.S.C. § 103(a) based on
`Noyes in view of VPK and further in view of Ramachandran. ..........51
`
`Ground 6: Claims 33, 41, 73, 212, 225, and 233 would have
`been obvious under 35 U.S.C. § 103(a) based on VPK in view
`of Metzgar. ..........................................................................................56
`
`XI. Conclusion .....................................................................................................60
`
`iii
`
`

`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`
`
`Cases
`Ariad Pharm., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) .......................................................................... 41
`
`ButamaxTM Advanced Biofuels LLC v. Gevo, Inc.,
`IPR2013-00539, paper no. 33 (PTAB March 3, 2015) ...................................... 40
`
`Continental Can Co. v. Monsanto Co.,
`948 F.2d 1264 (Fed.Cir.1991) ............................................................................ 16
`
`In re Cruciferous Sprout Litig.,
`301 F.3d 1343 (Fed.Cir. 2002) ........................................................................... 15
`
`Eli Lilly & Co. v. Barr Labs.,
`251 F.3d 955 (Fed. Cir. 2001) ............................................................................ 16
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................ 33
`
`In re Huang,
`100 F.3d 135 (Fed. Cir. 1996) ............................................................................ 59
`
`Institut Pasteur & Universite Pierre et Marie Curie v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) .......................................................................... 59
`
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................................... 59
`
`KSR Int’l Co. v Teleflex Inc.,
`550 U.S. 398 (2007) .....................................................................................passim
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 34
`
`iv
`
`

`
`Leapfrog Enterprises Inc. v. Fisher-Price Inc.,
`485 F.3d 1157 (Fed. Cir. 2007) .......................................................................... 60
`
`LizardTech v. Earth Resource Mapping, Inc.,
`424 F.3d 1336 (Fed. Cir. 2005) .......................................................................... 42
`
`Lockwood v. American Airlines, Inc.,
`107 F.3d 15¶ (Fed. Cir. 1997) ............................................................................. 44
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................ 59
`
`In re O’Farrell,
`853 F.2d 894 (Fed. Cir. 1988) ............................................................................ 34
`
`In re Omeprazole Patent Litigation,
`483 F.3d 1364 (Fed.Cir. 2007) ........................................................................... 15
`
`Purdue Pharma LP v. Faulding Inc.,
`230 F.3d 1320 (Fed. Cir. 2013) .................................................................... 43, 44
`
`Rambus Inc. v. Rea,
`731 F.3d 1248 (Fed. Cir. 2013) .......................................................................... 59
`
`Schering Corp. v. Geneva Pharmaceuticals,
`339 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 29
`
`Technology Licensing Corp. v. Videotek, Inc.,
`545 F.3d 1316 (Fed. Cir. 2008) .................................................................... 41, 44
`
`Trintec Indus., Inc. v. Top-U.S.A. Corp.,
`295 F.3d 1292 (Fed. Cir. 2002) .................................................................... 16, 29
`
`Tronzo v. Biomet,
`156 F.3d 1154 (Fed. Cir. 1998) .......................................................................... 44
`
`Vas-Cath Inc. v. Mahurkar,
`935 F.2d 1555 (Fed. Cir. 1991) .......................................................................... 41
`
`Verizon Services Corp. v. Cox Fibernet Virginia, Inc.,
`602 F.3d 1325 (Fed. Cir. 2010) .......................................................................... 16
`
`v
`
`

`
`In re Wesslau,
`353 F.2d 238 (CCPA 1965) ................................................................................ 34
`
`Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC,
`683 F.3d 1356 (Fed. Cir. 2012) .......................................................................... 59
`
`Federal Statutes
`
`35 U.S.C. § 102 ........................................................................................................ 15
`
`35 U.S.C. §102(a) .................................................................................................... 40
`
`35 U.S.C. § 102(b) ............................................................................................passim
`
`35 U.S.C. § 103 ........................................................................................................ 40
`
`35 U.S.C. § 103(a) ............................................................................................passim
`
`35 U.S.C. § 112 .................................................................................................. 41, 43
`
`35 U.S.C. § 120 ........................................................................................................ 42
`
`35 U.S.C. § 311 .......................................................................................................... 4
`
`Regulations
`
`37 C.F.R. § 42.8(b) .................................................................................................... 2
`
`37 C.F.R. §§ 42.100 ................................................................................................... 1
`
`37 C.F.R. § 42.100(b) .............................................................................................. 12
`
`37 C.F.R. § 42.104(a) ................................................................................................. 1
`
`37 C.F.R. § 42.104(b)(4) .................................................................................... 12, 15
`
`37 C.F.R. § 42.104(b)(5) .......................................................................................... 15
`
`Other Authorities
`
`M.P.E.P. § 2287(III)................................................................................................... 4
`
`vi
`
`

`
`LIST OF EXHIBITS
`
`Description
`Exhibit
`Ex. 1001 U.S. Patent No. 7,064,197 (issued June 20, 2006) ("the ' 197 Patent").
`Ex. 1002 Declaration of Dr. Norman Nelson (including his CV as Exhibit A).
`Ex. 1003 Excerpt from File History of the '197 Patent (Amendment dated
`October 31, 2003).
`Ex. 1004 U.S. Appl. No. 06/461,469 ("the '469 application").
`Ex. 1005 File History of U.S. Appl. No. 061732,374 ("the '374 application").
`Ex. 1006 Falk Fish and Morris Ziff, "A Sensitive Solid Phase
`Microradioimmunoassay For Anti-Double Stranded DNA Antibodies,"
`Arthritis and Rheumatism, Vol. 24, No.3 (March 1981) ("Fish").
`Ex. 1007 Barbara E. Noyes and George R. Stark, "Nucleic Acid Hydribization
`Using DNA Covalently Coupled to Cellulose," Cell, vol. 5, 301-310
`(July 1975) ("Noyes").
`Ex. 1008 A. C. Van Prooijen-Knegt, et al. "In Situ Hybridization of DNA
`Sequences in Human Metaphase Chromosomes Visualized by an
`Indirect Fluorescent Immunocytochemical Procedure." Experimental
`Cell Research 141, 397-407 (October 1982) ("VPK").
`Ex. 1009 U.S. Patent No. 5,572,892 (patented March 30, 1971) ("Metzgar").
`Ex. 1010 District court's Claim Construction Order for terms in the ' 197 Patent.
`Ex. 1011 Excerpt from File History of the ' 197 Patent (Communication dated
`August 10, 2007, and associated Exhibit 6).
`Ex. 1012 Submission in EP Patent 0117440 (App. 84100836.0-2106) dated June
`7, 2000.
`Ex. 1013 Excerpt from File History of the ' 197 Patent (Amendment dated May
`25, 2005).
`Ex. 1014 Excerpt from File History of the ' 197 Patent (Office Action dated
`September 29, 2005).
`Ex. 1015 A. C. Van Prooijen-Knegt, et al. "Spreading and staining of human
`metaphase chromosomes on aminoalkylsilane-treated glass slides."
`Histochemical Journal 14, 333-344 (1982).
`Ex. 1016 Excerpt from File History of EP Patent 0117440 (Enzo November 3,
`1997, Submission).
`Ex. 1017 Taylor et al., "Impact of surface chemistry and blocking strategies on
`DNA microarrays," Nucleic Acids Research, Vol. 31,2003.
`Ex. 1018 Aotsuka et al., "Measurement of anti-double stranded DNA Antibodies
`in major immunoglobulin classes." Journal of Immunological Methods,
`28, 149-62 (1979).
`
`..
`Vll
`
`

`
`Description
`Exhibit
`Ex. 1019 P. T. Gilham, "Immobilized Polynucleotides and Nucleic Acids,"
`published in Immobilized Biochemicals and Affinity Chromatography
`(R. B. Dunlap (ed.)), 1974 (Ex. 1019) ("Gilham").
`Ex. 1020 U.S. Patent Publication No. 2002/0164626 to Diehl et al., published
`November 7, 2002.
`Ex. 1021 Diehl et al., "Manufacturing DNA m1croarrays of high spot
`homogeneity and reduced background signal," Nucleic Acids Research,
`Vol. 31 , 2001.
`Ex. 1022 Excerpt from File History of the ' 197 Patent (Office Action dated
`November 26, 2004).
`Ex. 1023 Patent Owner's Opening Claim Construction Brief for terms in the ' 197
`Patent filed June 24, 2014 in related litigations.
`Ex. 1024 Excerpt from the ' 197 Patent File History (Supplemental amendment
`filed November 8, 2005).
`Ex. 1025 Excerpt from the '197 Patent File History (Response filed June 30,
`2004).
`Ex. 1026 Excerpt from the ' 197 Patent File History (Response filed September
`27, 1991).
`Ex. 1027 Assignment record of the
`database.
`Ex. 1028 K. B. Ramachandran and D. D. Perlmutter, "Effects of Immobilization
`of the Kinetics of Enzyme-Catalyzed Reactions. I. Glucose Oxidase in
`a Recirculation Reactor System," Biotechnology and Bioengineering,
`Vol. XVIII, 669-684 (1976) ("Ramachandran").
`Ex. 1029 Excerpt from the EP Patent 0117440 File History (Enzo submission
`filed December 28, 1994).
`Ex. 1030 Excerpt from the ' 197 Patent File History (Response filed July 30,
`1999).
`Ex. 1031 Excerpt from the ' 197 Patent File History (Office Action dated
`December 12, 1998).
`Ex. 1032 Webpage of Pat Brown Lab in Stanford University showing preparation
`of PLL (http:/ I cmgm. stanford. edu/pbrown/protocols/ 1_ slides .html), last
`visited March 30, 2016.
`Ex. 1033 Technical bulletin from Sigma-Aldrich providing information on poly-
`L-lysine (PLL).
`
`' 197 Patent from USPTO assignment
`
`vm
`
`

`
`I.
`
`Introduction
`Petitioner Hologic, Inc. (“Hologic”) requests inter partes review (“IPR”) of
`
`claims 1, 6, 8, 9, 12, 13, 14, 15, 16, 27, 31, 32, 33, 34, 38, 41, 61, 62, 63, 64, 68,
`
`69, 70, 72, 73, 74, 78, 79, 100, 101, 191, 192, 193, 194, 195, 212, 213, 218, 219,
`
`222, 225, 226, 227, 230, 233, and 236 (“the challenged claims”) of U.S. Patent No.
`
`7,064,197 (“the ’197 Patent”) (Ex. 1001) assigned to Enzo Life Sciences, Inc.
`
`(“Patent Owner” or “Enzo”) (Reel 17133, Frame 718) under 35 U.S.C. §§ 311-319
`
`and 37 C.F.R. §§ 42.100 et seq. See Ex. 1027 (assignment record from USPTO
`
`assignment database showing that the ’197 Patent is assigned to Enzo Life
`
`Sciences, Inc.). This Petition demonstrates there is a reasonable likelihood that
`
`Petitioner will prevail in proving, by a preponderance of the evidence, that the
`
`challenged claims of the ’197 patent are unpatentable over prior art not considered
`
`during prosecution. The challenged claims of the ’197 patent, as set forth above in
`
`this paragraph, should be found unpatentable and canceled.
`
`II. Grounds for Standing
`Petitioner certifies that the ’197 Patent is available for IPR and that the
`
`Petitioner is not barred or estopped from requesting IPR challenging the ’197
`
`Patent on the grounds identified. See 37 C.F.R. § 42.104(a). Specifically: (1)
`
`Petitioner is not the owner of the ’197 Patent; (2) Petitioner is not barred or
`
`estopped from requesting IPR; and (3) this Petition is being filed not more than one
`
`1
`
`

`
`year after Petitioner was served with a complaint alleging infringement of the ' 197
`
`Patent.
`
`Ill. Mandatory Notices Under 37 C.F.R. § 42.8(b)
`
`A.
`
`Real Party-In-Interest
`
`Hologic and Gen-Probe Incorporated are the real parties-in-interest.
`
`B.
`
`Related Matters
`
`Petitioner identifies the following judicial proceedings in which the ' 197
`
`Patent has been asserted as related matters. "DED" in the list below stands for
`
`District of Delaware.
`
`Caption
`Enzo Life Sciences, Inc. v. Hologic, Inc.
`
`Filed
`Dist.
`Number
`1-15-cv-00271 DED Mar. 27, 201 5
`
`Enzo Life Sciences, Inc. v. Siemens
`
`1-12-cv-00505 DED Apr. 20, 2012
`
`Healthcare Diagnostics, Inc.
`
`Enzo Life Sciences, Inc. v. Affymetrix, Inc.
`
`1-12-cv-00433 DED Apr. 6, 2012
`
`Enzo Life Sciences, Inc. v. Agilent
`
`1-12-cv-00434 DED Apr. 6, 2012
`
`Technologies Inc.
`
`Enzo Life Sciences, Inc. v. !!lumina Inc.
`
`1-12-cv-00435 DED Apr. 6, 2012
`
`Enzo Life Sciences, Inc. v. Abbott
`
`1-12-cv-00274 DED Mar. 6, 201 2
`
`Laboratories et al.
`
`Enzo Life Sciences, Inc. v. Becton Dickson
`
`1-12-cv-00275 DED Mar. 6, 201 2
`
`2
`
`

`
`Caption
`and Company et al.
`
`Number
`
`Dist.
`
`Filed
`
`Enzo Life Sciences, Inc. v. Life
`
`1-12-cv-00 105 DED Jan. 30, 2012
`
`Technologies Corporation
`
`Enzo Life Sciences, Inc. v. Roche
`
`1-12-cv-00 106 DED Jan. 30, 2012
`
`Molecular Systems Inc. et al.
`
`Petitioner has requested inter partes review of claims 17, 19, 25, 105, 106,
`
`113, 114, 116, 119, 120, 128, 129, 130, 13 1, 150, 151 , 152, 154, 178, 180, 185,
`
`186, 187, and 189 of the '197 Patent in another petition (Case No. IPR2016-00822)
`
`filed on March 30, 2016.
`
`IV. Lead and Back-up Counsel; Electronic Service
`
`Lead counsel isM. Paul Barker (Reg. No. 32, 013),
`
`paul.barker@finnegan.com, (650)849-6620. Backup counsel are Arpita
`
`Bhattacharyya (Reg. No. 63,681), arpita.bhattacharyya@finnegan.com, (617)646-
`
`1676 and Thomas L. Irving (Reg. No. 28,619), tom.irving@finnegan.com,
`
`(202)408-4082.
`
`Petitioner consents to electronic service of all documents at
`
`hologicipr@finnegan.com.
`
`V.
`
`Fee Payment
`
`The required fees are submitted under 37 C.F.R. §§ 42. 103(a) and 42.15(a).
`
`3
`
`

`
`If any additional fees are due during this proceeding, the Office may charge such
`
`fees to Deposit Account No. 06–0916.
`
`VI. Statement of Precise Relief Requested
`A. Claims for Which Review is Requested1
`Petitioner requests IPR and cancelation of claims 1, 6, 8, 9, 12, 13, 14, 15,
`
`16/1, 16/12, 16/13, 16/14, 16/15, 27, 31, 32/1, 33/1, 34/1, 38/1, 41/1, 61/1, 62/1,
`
`63/1, 64/1, 68, 69, 70, 72/6, 72/8, 72/9, 73/6, 73/8, 73/9, 74/6, 74/8, 74/9, 78/6,
`
`78/8, 79/6, 79/8, 79/9, 100/6, 100/9, 101/6, 101/9, 191, 192, 193, 194, 195,
`
`212/27, 213/27, 218/27, 219/27, 222/27, 225/27, 226/12, 226/13, 226/14, 226/15,
`
`227/8, 227/9, 230/6, 230/8, 230/9, 233/6, 233/8, 233/9, and 236/1 of the ’197
`
`Patent under 35 U.S.C. § 311.
`
`B.
`
`Statutory Grounds of Challenge
`
`The challenged claims are unpatentable and should be canceled in view of
`
`the following prior art references and grounds of unpatentability:
`
`
`
`
`1 Taking guidance from M.P.E.P. § 2287(III) (which discusses how to treat
`
`multiple dependent claims in reexamination proceedings), Petitioner represents the
`
`challenged multiple dependent claims as “x/y” where x is the dependent claim
`
`number and y is the claim from which x depends.
`
`4
`
`

`
`Prior Art References
`
`Ref. 1:
`
`Falk Fish et al., "A Sensitive Solid Phase Microradioimmunoassay
`
`For Anti-Double Stranded DNA Antibodies," Arthritis and
`
`Rheumatism, Vol. 24, No.3 (March 1981) ("Fish") (Ex. 1006).
`
`Ref. 2:
`
`P. T. Gilham, "Immobilized Polynucleotides and Nucleic Acids,"
`
`published in Immobilized Biochemicals and Affinity Chromatography
`
`(R. B. Dunlap (ed.)), 1974 ("Gilham") (Ex. 101 9).
`
`Ref. 3:
`
`A. C. Van Prooijen-Knegt, et al. "In Situ Hybridization of DNA
`
`Sequences in Human Metaphase Chromosomes Visualized by an
`
`Indirect Fluorescent Immunocytochemical Procedure." Experimental
`
`Cell Research 141, 397-407 (October 1982) ("VPK") (Ex. 1008).
`
`Ref. 4
`
`U.S. Pat. No. 5,572,892 (March 30, 1971) ("Metzgar") (Ex. 1009)
`
`Ref. 5
`
`Barbara E. Noyes et al., "Nucleic Acid Hybridization Using DNA
`
`Covalently Coupled to Cellulose," Cell, vol. 5, 301-310 (July 1975)
`
`("Noyes") (Ex. 1 007).
`
`Ref. 6
`
`K. B. Ramachandran et al., "Effects of Immobilization of the
`
`Kinetics of Enzyme-Catalyzed Reactions. I. Glucose Oxidase in a
`
`Recirculation Reactor System," Biotechnology and Bioengineering,
`
`Vol. XVIII, 669-684 (1 976) ("Ramachandran") (Ex. 1028).
`
`5
`
`

`
`Grounds
`
`Grounds of U npatentability
`
`Claims 1, 6, 8, 9, 12, 13, 14, 15, 1611, 16112, 16113, 16114, 16115, 27,
`
`31 ' 3211 ' 3311 ' 3411' 4111' 6111' 6211 ' 6311 ' 68, 69' 70, 72/6, 72/8,
`
`72/9, 73/6, 73/8, 73/9, 74/6, 74/8, 74/9, 79/6, 79/8, 79/9, 100/6, 100/9,
`
`1
`
`191 , 192, 193, 194, 212/27, 213/27, 219/27, 222/27, 225/27, 226112,
`
`226113, 226114, 226115, 227/8, 227/9, 230/6, 230/8, 230/9, 233/6,
`
`233/8, 233/9 and 23611 are anticipated under 35 U.S.C. § 102(b) by
`
`Fish (Ex. 1 006).
`
`2
`
`3
`
`Claims 31, 6411, 68, 10116, 101/9, 192, and 195 are obvious under 35
`
`U.S.C. § 103(a) based on Fish.
`
`Claims 3811, 78/6, 78/8, and 218/27 are obvious under 35 U.S.C.
`
`§ 103(a) based on Fish in view of Gilham.
`
`Claims 1, 6, 8, 9, 12, 13, 14, 15, 27, 31, 3211, 3411, 6111 , 62/1, 6311,
`
`68, 69, 70, 72/6, 72/8, 72/9, 74/6, 74/8, 74/9, 79/6, 79/8, 79/9, 100/6,
`
`4
`
`100/9, 191 , 192, 193, 194, 213/27, 219/27, 22611 2, 226113, 226114,
`
`226115, 227/8, 227/9, and 23611 are anticipated under 35 U.S.C.
`
`§ 1 02(b) by VPK.
`
`Claims 1611 , 16112, 16/13, 16114, 16115, 3811, 6411 , 78/6, 78/8, 10116,
`
`5
`
`10119, 195, 218/27, 222/27, 230/6, 230/8, and 230/9 are obvious
`
`under 35 U.S.C. § 103(a) based on VPK in view ofNoyes and further
`
`6
`
`

`
`Grounds
`
`Grounds of U npatentability
`
`in view of Ramachandran.
`
`Claims 3311, 4111, 73/6, 73/8, 73/9, 212/27, 225/27, 233/6, 233/8, and
`
`6
`
`233/9 are obvious under 35 U.S.C. § 103(a) based on VPK in view of
`
`Metzgar.
`
`C.
`
`Level of Ordinary Skill in the Art at the Time of the Claimed Invention
`
`The ' 197 Patent has a purported effective filing date of January 27, 1983,
`
`based on the filing date of Application No. 06/461 ,469-the earliest application in
`
`the priority chain of the '197 Patent. A continuation-in-part (CIP) application was
`
`purportedly filed on May 9, 1985 (the " 1985 CIP Application"). As discussed
`
`below, none of the claims of the ' 197 Patent challenged in this IPR are entitled to
`
`the January 27, 1983 filing date. Petitioner, however, in a great abundance of
`
`caution, advances separate grounds in view of both of the 1983 and 1985 dates.
`
`The application field for the '197 patent is nucleic acid chemistry, including
`
`techniques for attaching nucleic acids to other moieties like solid supports or
`
`labels. A person having ordinary skill in this field (POSIT A) as of both the 1983
`
`and the 1985 filing dates would have (i) possessed or would have been actively
`
`pursuing an advanced degree in organic chemistry and/or biochemistry, (ii)
`
`attained at least two years of experience in a chemistry or biochemistry laboratory
`
`7
`
`

`
`and would have been familiar with nucleic acid chemistry, and (iii) have been
`
`knowledgeable of conventional techniques for attaching nucleic acids to other
`
`moieties like solid supports or labels. See Ex. 1002 at ¶21. This level of skill of
`
`the POSITA would have applied to all obviousness analyses in this
`
`Petition. Furthermore, all conclusions regarding obviousness apply as of the
`
`January 27, 1983, and May 9, 1985 filing dates, as well as one year prior to
`
`each date (January 27, 1982, and May 9, 1984).
`
`VII. Prosecution History of the ’197 Patent and the State of the Art
`A. Hybridizable Nucleic Acids Bound to Solid Supports
`As a POSITA would have known, two strands of nucleic acids hybridize to
`
`one another through hydrogen bonding between complementary nucleotides
`
`(bases) that naturally pair with one another. Ex. 1002 ¶24. Under the Watson-Crick
`
`base pairing model, the nucleotide “A” pairs with the nucleotide “T” on the
`
`opposite strand, and the nucleotide “C” pairs with the nucleotide “G” on the
`
`opposite strand. Id. In RNA molecules, “T” is replaced by “U” to form an “A-U”
`
`base pair.
`
`More than a year before the January 27, 1983, filing date of the first
`
`application, multiple techniques were available to the POSITA for binding single
`
`stranded nucleic acids in a hybridizable form to many different types of solid
`
`supports. Ex. 1002, ¶25. Exemplary uses of hybridizable single-stranded nucleic
`
`8
`
`

`
`acids bound to solid supports included identifying biological materials in samples
`
`and separating biological materials from samples. Id.
`
`Summary of Prosecution History
`
`B.
`During lengthy prosecution of the applications leading up to issuance of the
`
`’197 Patent, the Patent Owner apparently realized that it would not obtain claims
`
`encompassing porous solid supports in view of the extensive publications
`
`involving routine techniques such as dot or blot hybridization, Southern and
`
`Northern hybridizations, and nucleic acid affinity columns. See, e.g., Ex. 1005 at
`
`75-82 (Office Action in Appl. No. 06/732,374, rejecting claims based on Falkow et
`
`al., which the Examiner argued discloses polynucleotides immobilized on solid
`
`supports). Therefore, the Patent Owner amended the claims to require non-porous
`
`solid supports to distinguish them from documents that disclosed porous solid
`
`supports. Id. at pp. 84, 89-91.
`
`But after many rounds of claim amendments, the Patent Owner still faced
`
`prior art rejections in view of known in-situ hybridization techniques, which were
`
`performed on non-porous solid supports such as microscope slides. Ex. 1022 at pp.
`
`10-12 (Office Action rejecting the claims as anticipated by U.S. Patent No.
`
`4,732,847 to Stuart et al.). The in-situ hybridization prior art patent (Stuart) applied
`
`by the Examiner did not explicitly state the mechanism that bound the nucleic
`
`acids to the non-porous solid supports.
`
`9
`
`

`
`The Patent Owner then looked to the exemplary and conventional nucleic
`
`acid binding chemistry in its examples to allege that it was the first to use three
`
`chemical groups (amines, hydroxyls, or epoxides) on a non-porous solid support to
`
`attach hybridizable single-stranded nucleic acids to the solid support. Ex. 1013, p.
`
`4 (exemplary claim amendment of claim 3144 to recite that the claimed “non-
`
`porous solid support” comprises “one or more amine(s), hydroxyl(s) or epoxide(s)
`
`thereon” and that the fixation or immobilization of the nucleic acids is “via said
`
`one or more amine(s), hydroxyl(s) or epoxide(s)” and pp. 47 and 97-98 where the
`
`Patent Owner used that limitation to distinguish the claims over the Stuart patent).
`
`Failing to recognize prior art that showed attachment of nucleic acids in a
`
`hybridizable form to non-porous solid supports through at least one of those
`
`chemical groups, the Examiner allowed the claims. Ex. 1014, p. 3.
`
`Specification of the ’197 Patent
`
`C.
`The ’197 Patent describes non-porous solid supports with fixed or
`
`immobilized nucleic acids, and systems and arrays comprising such non-porous
`
`solid supports. Ex. 1001, Title and Abstract. The ’197 Patent discusses non-porous
`
`solid supports such as “glass, or alternatively, plastic, polystyrene, polyethylene,
`
`dextran, polypropylene, and like.” Ex. 1001, 6:2-6; 12:39-45. The ’197 Patent also
`
`identifies conventional microtiter well plates as non-porous solid supports to which
`
`nucleic acids can be fixed. Id. at 12:54-58. The patent also discusses glass plates
`
`10
`
`

`
`having “an array of depressions or wells” (id. at 8:65-9:5), and polystyrene plates
`
`(id. at 11:56-58; 12:7-26) as solid supports to which nucleic acids may be bound
`
`(fixed or immobilized). The Patent Owner also argued that the ’197 Patent
`
`describes treatment of the solid supports with amine providing compounds, epoxy
`
`compounds, and acid solutions to fix or immobilize nucleic acids. Ex. 1011 at pp
`
`40-41 (providing citations to the application for support); Ex. 1001 at Abstract
`
`(note that the Abstract discussing the three groups was not added until November
`
`8, 2005 (Ex. 1024 at pp. 50 and 52). The ’197 Patent also explains that
`
`polynucleotide analyte sequences fixed or immobilized to the solid supports may
`
`be hybridized to complementary polynucleotide or oligonucleotide probes. See
`
`e.g., Ex. 1001 at 5:61-6:9; 6:15-27; 8:65-9:5. Although not required by any of the
`
`challenged claims, the hybridizing probe may have a label capable of generating a
`
`soluble signal, and hybridization of the probe to the analyte may be detected or
`
`quantified using the soluble signal. Id. at 1:23-32; 6:15-32; 8:65-9:12.
`
`This Petition will show that the non-porous solid supports and systems
`
`claimed in the ’197 Patent previously had been disclosed in prior art not considered
`
`during prosecution of the applications leading to the ’197 Patent. The prior art
`
`shows every limitation of the challenged claims, including the limitations added to
`
`secure allowance of the patent.
`
`11
`
`

`
`VIII. Claim Construction
`In an IPR, an unexpired patent’s claims generally receive the “broadest
`
`reasonable construction in light of the specification of the patent in which it
`
`appears.” 37 C.F.R. § 42.100(b). Unless otherwise noted, Petitioner proposes that
`
`the claim terms of the ’197 Patent be given their ordinary and customary meanings
`
`in the art. Petitioner, however, construes the following terms according to the
`
`intrinsic evidence and traditional canons of claim construction. Petitioner uses
`
`these constructions in its grounds for unpatentability. See 37 C.F.R. § 42.104(b)(4).
`
`“Non-Porous Solid Support”
`
`A.
`All challenged independent claims, i.e., claims 1, 6, 8, 9, 12, 13, 14, 15, and
`
`27, recite the term “non-porous solid support.” Ex. 1001 (claims). This term should
`
`be given its ordinary and customary meaning in the art. And as admitted by the
`
`Patent Owner, certain solid supports were known in the art to be non-porous. For
`
`example, the ’197 patent states that a polynucleotide can be fixed “to a non-porous
`
`solid support, such as a conventional microtiter well . . . .” Ex. 1001, 12:54-61.
`
`Similarly, when arguing that its counterpart Europea