0006675.00329US1
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`___________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`___________
`
`BECTON, DICKINSON AND COMPANY,
`Petitioner
`
`v.
`
`ENZO LIFE SCIENCES, INC.
`Patent Owner
`
`___________
`
`Case IPR2017-00172
`
`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
`
`
`
`
`
`

`
`
`
`TABLE OF CONTENTS
`
`I. 
`Introduction
`Grounds for Standing
`II. 
`III.  Mandatory Notices Under 37 C.F.R. § 42.8(b)
`A. 
`Real Party-In-Interest
`B. 
`Related Matters
`C. 
`Lead and Back-up Counsel; Postal, Hand-Delivery, and
`Electronic Service
`Fee Payment
`D. 
`VI.  Statement of Precise Relief Requested
`A. 
`Claims for Which Review is Requested
`B. 
`Statutory Grounds of Challenge
`C. 
`Level of Ordinary Skill in the Art at the Time of the Claimed
`Invention
`VII.  Prosecution History of the ’197 Patent and the State of the Art
`A.  Hybridizable Nucleic Acids Bound to Solid Supports
`B. 
`Summary of Prosecution History
`C. 
`Specification of the ’197 Patent
`VIII.  Claim Construction
`A. 
`“Non-Porous Solid Support”
`B. 
`“Hybridizable form”
`IX.  The Challenged Claims of the ’197 Patent Are Unpatentable
`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, 193, 194,
`212, 213, 219, 222, 225, 226, 227, 230, 233, and 236 are
`anticipated by Fish.
`1. 
`Independent claims 1, 6, 8, 9, 12, 13, 14, 15, and 27
`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.
`
`Page
`
`1 
`1 
`2 
`2 
`2 
`
`3 
`4 
`4 
`4 
`5 
`
`8 
`9 
`9 
`10 
`11 
`13 
`13 
`15 
`16 
`
`16 
`18 
`
`31 
`
`
`
`i
`
`

`
`35 
`
`39 
`
`41 
`
`41 
`
`47 
`
`53 
`55 
`56 
`57 
`
`57 
`
`59 
`61 
`
`
`
`B. 
`
`C. 
`
`2. 
`
`E. 
`
`F. 
`
`Ground 2: Claims 31, 64, 68, 101, 192, and 195 are obvious
`under 35 U.S.C. § 103(a) in view of Fish
`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.
`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.
`1. 
`The Challenged Claims Are Entitled to a Priority Date No
`Earlier Than the Filing of the CIP Application (Appl. No.
`06/732,374)
`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.
`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.
`1. 
`Claims 16, 222, and 230
`2. 
`Claims 38, 78, and 218
`3. 
`Claims 64, 101, and 195
`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.
`Secondary Considerations, Even if Considered, Fail to Overcome the
`Evidence of Obviousness
`XI.  Conclusion
`
`X. 
`
`
`
`ii
`
`
`
`
`
`

`
`
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Federal Cases
`Ariad Pharm., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) .......................................................................... 43
`
`ButamaxTM Advanced Biofuels LLC v. Gevo, Inc.,
`IPR2013-00539 (P.T.A.B. March 3, 2015) ........................................................ 42
`
`Continental Can Co. v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir.1991) ........................................................................... 17
`
`In re Cruciferous Sprout Litig.,
`301 F.3d 1343 (Fed. Cir. 2002) .......................................................................... 17
`
`Eli Lilly & Co. v. Barr Labs.,
`251 F.3d 955 (Fed. Cir. 2001) ............................................................................ 17
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................ 35
`
`In re Huang,
`100 F.3d 135 (Fed. Cir. 1996) ............................................................................ 60
`
`Institut Pasteur & Universite Pierre et Marie Curie v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) .......................................................................... 60
`
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................................... 60
`
`KSR Int’l Co. v Teleflex Inc.,
`550 U.S. 398 (2007) .....................................................................................passim
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 35
`
`Leapfrog Enterprises Inc. v. Fisher-Price Inc.,
`485 F.3d 1157 (Fed. Cir. 2007) .......................................................................... 61
`
`LizardTech v. Earth Resource Mapping, Inc.,
`424 F.3d 1336 (Fed. Cir. 2005) .......................................................................... 44
`iii
`
`
`
`

`
`
`
`Lockwood v. American Airlines, Inc.,
`107 F.3d 1565 (Fed. Cir. 1997) .......................................................................... 46
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................ 61
`
`In re O’Farrell,
`853 F.2d 894 (Fed. Cir. 1988) ............................................................................ 35
`
`In re Omeprazole Patent Litigation,
`483 F.3d 1364 (Fed. Cir. 2007) .......................................................................... 17
`
`Purdue Pharma LP v. Faulding Inc.,
`230 F.3d 1320 (Fed. Cir. 2013) .......................................................................... 45
`
`Rambus Inc. v. Rea,
`731 F.3d 1248 (Fed. Cir. 2013) .......................................................................... 61
`
`Schering Corp. v. Geneva Pharmaceuticals,
`339 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 30
`
`Technology Licensing Corp. v. Videotek, Inc.,
`545 F.3d 1316 (Fed. Cir. 2008) .................................................................... 42, 46
`
`Trintec Indus., Inc. v. Top-U.S.A. Corp.,
`295 F.3d 1292 (Fed. Cir. 2002) .................................................................... 17, 30
`
`Tronzo v. Biomet,
`156 F.3d 1154 (Fed. Cir. 1998) .......................................................................... 46
`
`Vas-Cath Inc. v. Mahurkar,
`935 F.2d 1555 (Fed. Cir. 1991) .......................................................................... 43
`
`Verizon Services Corp. v. Cox Fibernet Virginia, Inc.,
`602 F.3d 1325 (Fed. Cir. 2010) .......................................................................... 17
`
`In re Wesslau,
`353 F.2d 238 (CCPA 1965) ................................................................................ 35
`
`Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC,
`683 F.3d 1356 (Fed. Cir. 2012) .......................................................................... 61
`
`
`
`iv
`
`

`
`
`
`Federal Statutes
`35 U.S.C. § 102 .................................................................................................passim
`
`35 U.S.C. § 103 .................................................................................................passim
`
`35 U.S.C. § 112 ............................................................................................ 42, 43, 44
`
`35 U.S.C. § 120 ........................................................................................................ 43
`
`35 U.S.C. § 311 .......................................................................................................... 4
`
`35 U.S.C. § 315(c) ..................................................................................................... 2
`
`Regulations
`
`37 C.F.R. § 42.8(b) .................................................................................................... 2
`
`37 C.F.R. § 42.15(a) ................................................................................................... 4
`
`37 C.F.R. § 42.22 ....................................................................................................... 2
`
`37 C.F.R. § 42.100(b) .............................................................................................. 13
`
`37 C.F.R. § 42.103(a) ................................................................................................. 4
`
`37 C.F.R. § 42.104(a) ................................................................................................. 1
`
`37 C.F.R. § 42.104(b)(4) .................................................................................... 13, 16
`
`37 C.F.R. § 42.104(b)(5) .......................................................................................... 16
`
`37 C.F.R. § 42.122(b) ................................................................................................ 2
`
`Other Authorities
`
`M.P.E.P. § 2287(III) ................................................................................................... 4
`
`
`
`
`
`
`
`v
`
`

`
`
`
`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. 06/732,374 (“the ’374 application”).
`Ex. 1006 Falk Fish and Morris Ziff, “A Sensitive Solid Phase Micro-
`radioimmunoassay 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 Hybridization
`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. 3,572,892 (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.
`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 Sept.
`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).
`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).
`
`Ex. 1016
`
`Ex. 1013
`
`
`
`vi
`
`

`
`
`
`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 microarrays 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 ’197 Patent from USPTO assignment
`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 8, 1998).
`Ex. 1032 Webpage of Pat Brown Lab in Stanford University showing
`preparation
`Technical bulletin from Sigma-Aldrich providing information on
`poly-L-lysine (PLL).
`
`Ex. 1033
`
`
`
`vii
`
`

`
`
`
`I.
`
`Introduction
`Petitioner Becton, Dickinson and Company (“BD”) 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 ’197Patent 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 an 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 an IPR; and (3) this Petition is being filed concurrently with a
`
`
`
`1
`
`

`
`
`
`proper Motion for Joinder under 35 U.S.C. § 315(c) and 37 C.F.R. §§ 42.22,
`
`42.122(b).
`
`III. Mandatory Notices Under 37 C.F.R. § 42.8(b)
`
`A. Real Party-In-Interest
`
`Becton, Dickinson and Company is the real party-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
`
`Number
`
`Dist.
`
`Filed
`
`Enzo Life Sciences, Inc. v. Hologic, Inc.
`
`l-15-cv-00271 DED Mar. 27, 2015
`
`Pending
`
`Enzo Life Sciences, Inc. v. Siemens
`
`l-12-cv-00505 DED Apr. 20, 2012
`
`Healthcare Diagnostics, Inc.
`
`Concluded
`
`Enzo Life Sciences, Inc. v. Affymetrix, Inc.
`
`l-12-cv-00433 DED Apr. 6, 2012
`
`Concluded
`
`Enzo Life Sciences, Inc. v. Agilent
`
`l-12-cv-00434 DED Apr. 6, 2012
`
`Technologies Inc.
`
`Concluded
`
`Enzo Life Sciences, Inc. v. Illumina Inc.
`
`l-12-cv-00435 DED Apr. 6, 2012
`
`Concluded
`
`
`
`2
`
`

`
`
`
`Caption
`
`Number
`
`Dist.
`
`Filed
`
`Enzo Life Sciences, Inc. v. Abbott
`
`l-12-cv-00274 DED Mar. 6, 2012
`
`Laboratories et al.
`
`Pending
`
`Enzo Life Sciences, Inc. v. Becton, Dickson
`
`l-12-cv-00275 DED Mar. 6, 2012
`
`and Company et al.
`
`Pending
`
`Enzo Life Sciences, Inc. v. Life Technologies
`
`l-12-cv-00105 DED Jan. 30, 2012
`
`Corporation
`
`Concluded
`
`Enzo Life Sciences, Inc. v. Roche
`
`1-12-CV-00106 DED Jan. 30, 2012
`
`Molecular Systems Inc. et al.
`
`Pending
`
`
`
`Petitioner has requested inter partes review of claims 17, 19, 25, 105, 106,
`
`113, 114, 116, 119, 120, 128, 129, 130, 131, 150, 151, 152, 154, 178, 180, 185, 186,
`
`187, and 189 of the ’197 Patent in another petition (Case No. IPR2017-00181) filed
`
`on November 3, 2016.
`
`Lead and Back-up Counsel; Postal, Hand-Delivery, and Electronic
`C.
`Service
`
`Lead counsel is Jamie T. Wisz (Reg. No. 58,429),
`
`Jamie.Wisz@WilmerHale.com, (tel.) (202) 663-6286, (fax) (202) 663-6363.
`
`Backup counsel is Heather Petruzzi (Reg. No. 71,270),
`
`Heather.Petruzzi@WilmerHale.com, (202) 663-6028, (fax) (202) 663-6363.
`
`Petitioner consents to postal and hand-delivery service of all documents at
`3
`
`
`
`

`
`
`
`WILMER CUTLER PICKERING HALE AND DORR LLP, 1875 Pennsylvania
`
`Ave., NW, Washington, DC 20006. Petitioner consents to electronic service of all
`
`documents.
`
`D.
`
`Fee Payment
`
`The required fees are submitted under 37 C.F.R. §§ 42.103(a) and 42.15(a).
`
`If any additional fees are due during this proceeding, the Office may charge such
`
`fees to Deposit Account No. 08-0219.
`
`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.
`
`
`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
`
`

`
`
`
`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 unpatentability2:
`
`
`
`
`2 Petitioner has included all of the Grounds originally submitted in Hologic Inc. v.
`
`Enzo Life Sciences, Inc., IPR2016-00820 (“the Hologic IPR”) in an effort to
`
`demonstrate that the issues presented herein are the same as those in the Hologic
`
`IPR. As explained further in Petitioner’s Motion for Joinder, filed concurrently
`
`with this Petition, Petitioner is only requesting institution of the Grounds already
`
`instituted in the Hologic IPR: Ground 1 (claims 1, 6, 8, 9, 12-16, 27, 32-34, 41,
`
`61-63, 69, 70, 72–74, 79, 100, 191, 193, 194, 212, 213, 219, 222, 225-227, 230,
`
`233, and 236 as anticipated by Fish (Ex. 1006)); Ground 2 (claims 31, 64, 68, 101,
`
`192, and 195 as obvious over Fish (Ex. 1006)); Ground 3 (claims 38, 78, and 218 as
`
`obvious over Fish (Ex. 1006) and Gilham (Ex. 1019)); Ground 4 (claims 1, 6, 8, 9,
`
`12–15, 27, 31, 32, 34, 61–63, 68–70, 72, 74, 79, 100, 191-193, 194, 213, 219, 226,
`
`227, and 236 as anticipated by VPK (Ex. 1008)); Ground 5 (claims 33, 41, 73, 212,
`
`225, and 233 as obvious over VPK (Ex. 1008) and Metzgar (Ex. 1009)); and Ground
`
`6 (claims 16, 38, 64, 78, 101, 195, 218, 222, and 230 as obvious over Noyes (Ex.
`
`1007), VPK (Ex. 1008), Metzgar (Ex. 1009), and Ramachandran (Ex. 1028)).
`
`
`
`5
`
`

`
`
`
`
`
`
`
`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. 1019).
`
`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. 1007).
`
`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 (1976) (“Ramachandran”) (Ex. 1028).
`
`6
`
`

`
`
`
`
`
`Grounds
`
`Grounds of Unpatentability
`
`1
`
`2
`
`3
`
`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, 41/1, 61/1, 62/1, 63/1, 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, 191, 192,
`
`193, 194, 212/27, 213/27, 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
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`and 236/1 are anticipated under 35 U.S.C. § 102(b) by Fish (Ex. 1006).
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`Claims 31, 64/1, 68, 101/6, 101/9, 192, and 195 are obvious under 35
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`U.S.C. § 103(a) based on Fish.
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`Claims 38/1, 78/6, 78/8, and 218/27 are obvious under 35 U.S.C. §
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`103(a) based on Fish in view of Gilham.
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`Claims 1, 6, 8, 9, 12, 13, 14, 15, 27, 31, 32/1, 34/1, 61/1, 62/1, 63/1, 68,
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`69, 70, 72/6, 72/8, 72/9, 74/6, 74/8, 74/9, 79/6, 79/8, 79/9, 100/6, 100/9,
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`4
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`191, 192, 193, 194, 213/27, 219/27, 226/12, 226/13, 226/14, 226/15,
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`227/8, 227/9, and 236/1 are anticipated under 35 U.S.C. § 102(b) by
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`VPK.
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`Claims 16/1, 16/12, 16/13, 16/14, 16/15, 38/1, 64/1, 78/6, 78/8, 101/6,
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`101/9, 195, 218/27, 222/27, 230/6, 230/8, and 230/9 are obvious under
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`35 U.S.C. § 103(a) based on VPK in view of Noyes and further in view
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`5
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`of Ramachandran.
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`Claims 33/1, 41/1, 73/6, 73/8, 73/9, 212/27, 225/27, 233/6, 233/8, and
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`6
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`233/9 are obvious under 35 U.S.C. § 103(a) based on VPK in view of
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`Metzgar.
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`Level of Ordinary Skill in the Art at the Time of the Claimed
`C.
`Invention
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`The ’197 Patent has a purported effective filing date of January 27, 1983,
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`based on the filing date of Application No. 06/461,469—the earliest application in
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`the priority chain of the ’197 Patent. A continuation-in-part (CIP) application was
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`purportedly filed on May 9, 1985 (the “1985 CIP Application”). As discussed
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`below, none of the claims of the ’197 Patent challenged in this IPR are entitled to the
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`January 27, 1983 filing date. Petitioner, however, in a great abundance of caution,
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`advances separate grounds in view of both of the 1983 and 1985 dates.
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`The application field for the ’197 patent is nucleic acid chemistry, including
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`techniques for attaching nucleic acids to other moieties like solid supports or labels.
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`A person having ordinary skill in this field (POSITA) as of both the 1983 and the
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`1985 filing dates would have (i) possessed or would have been actively pursuing an
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`advanced degree in organic chemistry and/or biochemistry, (ii) attained at least two
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`years of experience in a chemistry or biochemistry laboratory and would have been
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`familiar with nucleic acid chemistry, and (iii) have been knowledgeable of
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`conventional techniques for attaching nucleic acids to other moieties like solid
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`supports or labels. See Ex. 1002, ¶ 21. This level of skill of the POSITA would
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`have applied to all obviousness analyses in this Petition. Furthermore, all
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`conclusions regarding obviousness apply as of the January 27, 1983, and May 9,
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`1985 filing dates, as well as one year prior to each date (January 27, 1982, and May
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`9, 1984).
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`VII. Prosecution History of the ’197 Patent and the State of the Art
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`A. Hybridizable Nucleic Acids Bound to Solid Supports
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`As a POSITA would have known, two strands of nucleic acids hybridize to
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`one another through hydrogen bonding between complementary nucleotides (bases)
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`that naturally pair with one another. Ex. 1002, ¶ 24. Under the Watson-Crick base
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`pairing model, the nucleotide “A” pairs with the nucleotide “T” on the opposite
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`strand, and the nucleotide “C” pairs with the nucleotide “G” on the opposite strand.
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`Id. In RNA molecules, “T” is replaced by “U” to form an “A-U” base pair.
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`More than a year before the January 27, 1983, filing date of the first
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`application, multiple techniques were available to the POSITA for binding single
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`stranded nucleic acids in a hybridizable form to many different types of solid
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`supports. Ex. 1002, ¶ 25. Exemplary uses of hybridizable single-stranded nucleic
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`acids bound to solid supports included identifying biological materials in samples
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`and separating biological materials from samples. Id.
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`B.
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`Summary of Prosecution History
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`During lengthy prosecution of the applications leading up to issuance of the
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`’197 Patent, the Patent Owner apparently realized that it would not obtain claims
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`encompassing porous solid supports in view of the extensive publications involving
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`routine techniques such as dot or blot hybridization, Southern and Northern
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`hybridizations, and nucleic acid affinity columns. See, e.g., Ex. 1005, at 75-82
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`(Office Action in Appl. No. 06/732,374, rejecting claims based on Falkow et al.,
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`which the Examiner argued discloses polynucleotides immobilized on solid
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`supports). Therefore, the Patent Owner amended the claims to require non-porous
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`solid supports to distinguish them from documents that disclosed porous solid
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`supports. Id., pp. 84, 89-91.
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`But after many rounds of claim amendments, the Patent Owner still faced
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`prior art rejections in view of known in-situ hybridization techniques, which were
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`performed on non-porous solid supports such as microscope slides. Ex. 1022, pp.
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`10-12 (Office Action rejecting the claims as anticipated by U.S. Patent No.
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`4,732,847 to Stuart et al.). The in-situ hybridization prior art patent (Stuart) applied
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`by the Examiner did not explicitly state the mechanism that bound the nucleic acids
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`to the non-porous solid supports.
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`The Patent Owner then looked to the exemplary and conventional nucleic acid
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`binding chemistry in its examples to allege that it was the first to use three chemical
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`groups (amines, hydroxyls, or epoxides) on a non-porous solid support to attach
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`hybridizable single-stranded nucleic acids to the solid support. Ex. 1013, p. 4
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`(exemplary claim amendment of claim 3144 to recite that the claimed “non-porous
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`solid support” comprises “one or more amine(s), hydroxyl(s) or epoxide(s) thereon”
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`and that the fixation or immobilization of the nucleic acids is “via said one or more
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`amine(s), hydroxyl(s) or epoxide(s),” and pp. 47, 97-98 where the Patent Owner
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`used that limitation to distinguish the claims over the Stuart patent). Failing to
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`recognize prior art that showed attachment of nucleic acids in a hybridizable form to
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`non-porous solid supports through at least one of those chemical groups, the
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`Examiner allowed the claims. Ex. 1014, p. 3.
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`C.
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`Specification of the ’197 Patent
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`The ’197 Patent describes non-porous solid supports with fixed or
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`immobilized nucleic acids, and systems and arrays comprising such non-porous
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`solid supports. Ex. 1001, at Title and Abstract. The ’197 Patent discusses
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`non-porous solid supports such as “glass, or alternatively, plastic, polystyrene,
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`polyethylene, dextran, polypropylene, and like.” Ex. 1001, at 6:2-6; 12:39-45.
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`The ’197 Patent also identifies conventional microtiter well plates as non-porous
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`solid supports to which nucleic acids can be fixed. Id. at 12:54-58. The patent also
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`discusses glass plates having “an array of depressions or wells” (id. at 8:65-9:5), and
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`polystyrene plates (id. at 11:56-58; 12:7-26) as solid supports to which nucleic acids
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`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,
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`epoxy compounds, and acid solutions to fix or immobilize nucleic acids. Ex. 1011,
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`pp 40-41 (providing citations to the application for support); Ex. 1001 at Abstract
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`(note that the Abstract discussing the three groups was not added until November 8,
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`2005 (Ex. 1024, pp. 50 and 52). The ’197 Patent also explains that polynucleotide
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`analyte sequences fixed or immobilized to the solid supports may be hybridized to
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`complementary polynucleotide or oligonucleotide probes. See, e.g., Ex. 1001, at
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`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
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`signal, and hybridization of the probe to the analyte may be detected or quantified
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`using the soluble signal. Id. at 1:23-32; 6:15-32; 8:65-9:12.
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`This Petition will show that the non-porous solid supports and systems
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`claimed in the ’197 Patent previously had been disclosed in prior art not considered
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`during prosecution of the applications leading to the ’197 Patent. The prior art
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`shows every limitation of the challenged claims, including the limitations added to
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`secure allowance of the patent.
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`VIII. Claim Construction
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`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
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`appears.” 37 C.F.R. § 42.100(b). Unless otherwise noted, Petitioner proposes that
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`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
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`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
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`27, recite the term “non-porous solid support.” Ex. 1001 (claims). This term
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`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.
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`For example, the ’197 patent states that a polynucleotide can be fixed “to a
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`non-porous solid support, such as a conventional microtiter well . . . .” Ex. 1001, at
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`12:54-61. Similarly, when arguing that its counterpart European patent application
`
`disclosed non-porous solid supports—despite failing to mention the word
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`“non-porous”—the Patent Owner repeatedly asserted that containers in which
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`reactions take place in solution, such as the disclosed wells, must be non-porous.
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`Ex. 1016, pp. 6-7.
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`Also, the Patent Owner readily admitted that the prior art technique of in-situ
`
`hybridization was performed on glass slides, which necessarily are non-porous.
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`Ex. 1026, pp. 5, 7 (The Examiner argued that “a transparent non-porous solid
`
`support is embodied by glass slides,” as disclosed by Langer’s in-situ technique (p.
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`5), and the Patent Owner admitted that Langer et al. disclosed an in-situ
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`hybridization method that was performed on “nonporous solid supports that are
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`transparent or translucent.” (p. 7)).
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`And in its Opening Claim Construction Brief in the related litigations, the
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`Patent Owner noted that “non-porous” is a commonly understood term—citing the
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`Examiner’s understanding “that glass slides are ‘reasonably interpreted as the
`
`commonly utilized non-porous microscope type slides which are well known in the
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`art.’” Ex. 1023, pp. 8-9 (citing Ex. 1022 (11-26-2004 Office Action, p. 10)).
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`Thus, the ordinary and customary meaning of “non-porous solid support”
`
`should apply, which includes conventional laboratory equipment such as microtiter
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`wells and glass slides. In the related litigations involving the ’197 Patent, the
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`district court construed the term “non-porous” to mean “having no pores.” Ex.
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`1010, pp. 5-7. If adopted here, that construction would not change the conclusions
`
`in this Petition, because the prior art applied in this Petition shows conventional
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`microtiter wells and glass slides, which the Petitioner admits are encompassed by the
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`claim language “non-porous solid support.”
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`B.
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`“Hybridizable form”
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`The term “hybridizable form” is recited i