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.
`
`Real Party–In–Interest ........................................................................... 2
`
`IV. Related Matters ................................................................................................ 2
`
`V.
`
`Lead and Back-up Counsel; Electronic Service .............................................. 3
`
`VI. Fee Payment ..................................................................................................... 3
`
`VII. 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
`
`VIII. Summary of the Prosecution History of the ’197 Patent and the State
`of the Art .......................................................................................................... 8
`
`A. Hybridizable Nucleic Acids Bound to Solid Supports .......................... 8
`
`B.
`
`C.
`
`Specification of the ’197 Patent ............................................................ 8
`
`Summary of Prosecution History ........................................................10
`
`IX. Claim Construction ........................................................................................11
`
`A.
`
`B.
`
`C.
`
`“Non-Porous Solid Support” ...............................................................11
`
`“Hybridizable form” ............................................................................13
`
`“Array” ................................................................................................14
`
`X.
`
`The Challenged Claims of the ’197 Patent Are Unpatentable ......................14
`i
`
`

`
`A. Ground 1: Claims 17, 19, 25, 105, 106, 114, 116, 119, 128, 129,
`150, 152, 178, 180, 186, and 187 are anticipated by Fish ..................15
`
`1.
`
`2.
`
`Independent claims 17, 19, and 25 ...........................................16
`
`Dependent claims 105, 106, 114, 116, 119, 128, 129,
`150, 152, 178, 180, 186, and 187. .............................................27
`
`B. Ground 2: Claims 130, 131, 151, and 154 are obvious under 35
`U.S.C. § 103(a) in view of Fish. .........................................................30
`
`C. Ground 3: Claims 120 and 189 are obvious under 35 U.S.C.
`§ 103(a) based on Fish in view of Metzgar and further in view
`of Sato. .................................................................................................34
`
`D. Ground 4: Claims 113 and 185 would have been obvious under
`35 U.S.C. § 103(a) based on Fish in view of Gilham. ........................36
`
`E.
`
`Ground 5: Claim 17, 19, 25, 105, 106, 114, 119, 120, 128, 129,
`131, 150, 151, 152, 178, 180, 186, and 189 would have been
`obvious under 35 U.S.C. § 102(b) based on VPK in view of
`Metzgar. ...............................................................................................39
`
`1.
`
`2.
`
`3.
`
`4.
`
`The Challenged Claims Are Entitled to a Priority Date
`No Earlier Than the Filing of the CIP Application (Appl.
`No. 06/732,374) ........................................................................39
`
`The legal requirements for claiming priority ............................40
`
`The original disclosure of the 1983 application does not
`provide written description support for the element “non-
`porous solid support.” ...............................................................41
`
`Claims 17, 19, 25, 105, 106, 114, 119, 120, 128, 129,
`131, 150, 151, 152, 178, 180, 186, and 189 would have
`been obvious based on VPK in view of Metzgar. ....................45
`
`F.
`
`Ground 6: Claims 113, 116, 130, 154, 185, and 187 are obvious
`under 35 U.S.C. § 103(a) based on Noyes in view of VPK and
`further in view of Metzgar and Ramachandran...................................53
`
`XI. SECONDARY CONSIDERATIONS, EVEN IF CONSIDERED,
`FAIL TO OVERCOME THE EVIDENCE OF OBVIOUSNESS ................58
`ii
`
`

`
`XII. Conclusion .....................................................................................................60
`
`XII. Conclusion ................................................................................................... ..6O
`
`
`
`
`
`
`
`iii
`
`iii
`
`

`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Federal 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) ........................................................................... 16
`
`Eli Lilly & Co. v. Barr Labs.,
`251 F.3d 955 (Fed. Cir. 2001) ............................................................................ 16
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................ 30
`
`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) .......................................................................... 31
`
`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
`
`iv
`
`

`
`Lockwood v. American Airlines, Inc.,
`107 F.3d 1565 (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) ............................................................................ 31
`
`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
`
`Rambus Inc. v. Rea,
`731 F.3d 1248 (Fed. Cir. 2013) .......................................................................... 59
`
`In re Robertson,
`169 F.3d 743 (Fed. Cir. 1999) ............................................................................ 16
`
`Schering Corp. v. Geneva Pharmaceuticals,
`339 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 27
`
`Technology Licensing Corp. v. Videotek, Inc.,
`545 F.3d 1316 (Fed. Cir. 2008) .................................................................... 40, 44
`
`Trintec Indus., Inc. v. Top-U.S.A. Corp.,
`295 F.3d 1292 (Fed. Cir. 2002) .................................................................... 16, 27
`
`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
`
`In re Wesslau,
`353 F.2d 238 (CCPA 1965) ................................................................................ 31
`
`v
`
`

`
`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) ............................................................................................. 39, 40
`
`35 U.S.C. § 102(b) ............................................................................................passim
`
`35 U.S.C. § 103 .................................................................................................. 40, 58
`
`35 U.S.C. § 103(a) ............................................................................................passim
`
`35 U.S.C. § 112 ...................................................................................... 10, 11, 40, 41
`
`35 U.S.C. § 112, ¶ .................................................................................................... 10
`
`35 U.S.C. § 112, ¶ 1 ........................................................................................... 40, 42
`
`35 U.S.C. § 120 ........................................................................................................ 41
`
`35 U.S.C. § 311 .......................................................................................................... 4
`
`35 U.S.C. §§ 311-319................................................................................................. 1
`
`Regulations
`
`37 C.F.R. § 42.8(b) .................................................................................................... 2
`
`37 C.F.R. § 42.15(a) ................................................................................................... 3
`
`37 C.F.R. § 42.100(b) .............................................................................................. 11
`
`37 C.F.R. §§ 42.100 et seq. ........................................................................................ 1
`
`37 C.F.R. § 42.103(a) ................................................................................................. 3
`
`37 C.F.R. § 42.104(a) ................................................................................................. 1
`
`37 C.F.R. § 42.104(b)(4) .................................................................................... 11, 15
`
`37 C.F.R. § 42.104(b)(5) .......................................................................................... 15
`
`vi
`
`

`
`M.P.E.P. § 2287(III)................................................................................................... 4
`M.P.E.P. § 2287(1I1) ................................................................................................. ..4
`
`
`
`
`
`vii
`
`Vii
`
`

`
`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
`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).
`
`viii
`
`

`
`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 12, 1998).
`Ex. 1032 Webpage of Pat Brown Lab in Stanford University showing preparation
`of PLL (http://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).
`Ex. 1034 Sato et al., “Cell Surface Charge and Cell Division in Escherichia coli
`after X radiation.” Radiation Research 87, 646-656 (1981) (“Sato”).
`
`ix
`
`

`
`I.
`
`Introduction
`Petitioner Hologic, Inc. (“Hologic”) requests inter partes review (“IPR”) 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 (“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 (USPTO
`
`assignment record.) 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 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
`
`year after Petitioner was served with a complaint alleging infringement of the ’197
`
`Patent.
`
`1
`
`

`
`III. 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.
`
`IV. Related Matters
`Petitioner identifies the following judicial proceedings in which the ’197
`
`Patent has been asserted as related matters. “DED” stands for District of Delaware.
`
`Caption
`Enzo Life Sciences, Inc. v. Hologic, Inc.
`
`Filed
`Dist.
`Number
`1-15-cv-00271 DED Mar. 27, 2015
`
`1-12-cv-00505 DED Apr. 20, 2012
`
`
`
`1-12-cv-00433 DED Apr. 6, 2012
`
`Enzo Life Sciences, Inc. v. Siemens
`
`Healthcare Diagnostics, Inc.
`
`Enzo Life Sciences, Inc. v. Affymetrix,
`
`Inc.
`
`Enzo Life Sciences, Inc. v. Agilent
`
`1-12-cv-00434 DED Apr. 6, 2012
`
`Technologies Inc.
`
`Enzo Life Sciences, Inc. v. Illumina Inc.
`
`1-12-cv-00435 DED Apr. 6, 2012
`
`Enzo Life Sciences, Inc. v. Abbott
`
`1-12-cv-00274 DED Mar. 6, 2012
`
`Laboratories et al.
`
`Enzo Life Sciences, Inc. v. Becton
`
`1-12-cv-00275 DED Mar. 6, 2012
`
`Dickson and Company et al.
`
`Enzo Life Sciences, Inc. v. Life
`
`1-12-cv-00105 DED Jan. 30, 2012
`
`2
`
`

`
`Caption
`Technologies Corporation
`
`Number
`
`Dist.
`
`Filed
`
`Enzo Life Sciences, Inc. v. Roche
`
`1-12-cv-00106 DED Jan. 30, 2012
`
`Molecular Systems Inc. et al.
`
`
`
`Petitioner has requested inter partes review 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 of the ’197 Patent in another petition (Case No. IPR2016-00820) filed on
`
`March 30, 2016.
`
`V.
`
`Lead and Back-up Counsel; Electronic Service
`
`Lead counsel is M. 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.
`
`VI. 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. 06–0916.
`
`3
`
`

`
`VII. Statement of Precise Relief Requested
`A. Claims for Which Review Is Requested1
`Petitioner requests IPR and cancelation of claims 17, 19, 25, 105/17, 105/19,
`
`106/17, 106/19, 113/17, 113/19, 114/17, 114/19, 116/17, 116/19, 119/17, 119/19,
`
`120/17, 120/19, 128/17, 128/19, 129/17, 129/19, 130/17, 130/19, 131/17, 150,
`
`151,152, 154, 178/25, 180/25, 185/25, 186/25, 187/25, and 189/25 of the ’197
`
`Patent under 35 U.S.C. § 311.
`
`Statutory Grounds of Challenge
`
`B.
`The challenged claims are unpatentable and should be canceled in view of
`
`the following prior art references and grounds of unpatentability:
`
`Prior Art References
`
`Ref. 1:
`
`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. 1006).
`
`
`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. 2:
`
`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. 1007).
`
`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. Patent No. 5,572,892 (patented March 30, 1971) (“Metzgar”)
`
`(Ex. 1009)
`
`Ref. 5 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. 1028)
`
`Ref. 6
`
`Sato et al., “Cell Surface Charge and Cell Division in Escherichia coli
`
`after X radiation.” Radiation Research 87, 646-656 (1981) (“Sato”)
`
`5
`
`(Ex. 1034).
`
`
`
`

`
`Ground
`
`Grounds of Unpatentability
`
`1
`
`2
`
`3
`
`4
`
`Claims 17, 19, 25, 105/17, 105/19, 106/17, 106/19, 114/17, 114/19,
`
`116/17, 116/19, 119/17, 119/19, 128/17, 128/19, 129/17, 129/19,
`
`150,152, 178/25, 180/25, 186/25 and 187/25 are anticipated by Fish
`
`under 35 U.S.C. § 102(b).
`
`Claims 130/17, 130/19, 131/17, 151, and 154 are obvious under 35
`
`U.S.C. § 103(a) in view of Fish.
`
`Claims 120/17, 120/19 and 189/25 are obvious under 35 U.S.C.
`
`§ 103(a) based on Fish in view of Metzgar and further in view of Sato.
`
`Claims 113/17, 113/19 and 185/25 would have been obvious under 35
`
`U.S.C. § 103(a) based on Fish in view of Gilham.
`
`Claim 17, 19, 25, 105/17, 105/19, 106/17, 106/19, 114/17, 114/19,
`
`119/17, 119/19, 120/17, 120/19, 128/17, 128/19, 129/17, 129/19,
`
`5
`
`131/17, 150, 151, 152, 178/25, 180/25, 186/25, and 189/25 would have
`
`been obvious under 35 U.S.C. § 103(a) based on VPK in view of
`
`Metzgar.
`
`Claims 113/17, 113/19, 116/17, 116/19, 130/17, 130/19, 154, 185/25,
`
`6
`
`and 187/25 are obvious under 35 U.S.C. § 103(a) based on Noyes in
`
`view of VPK and further in view of Metzgar and Ramachandran.
`
`
`
`6
`
`

`
`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 is 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 (POSITA) 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
`
`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,
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`1983, and May 9, 1985 filing dates, as well as one year prior to each date (January
`
`27, 1983, and May 9, 1984).
`
`VIII. Summary of the Prosecution History of the ’197 Patent and the State of
`the Art
`A. Hybridizable Nucleic Acids Bound to Solid Supports
`As the 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”
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`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
`
`acids bound to solid supports included identifying biological materials in samples
`
`and separating biological materials from samples. Ex. 1002, ¶25.
`
`Specification of the ’197 Patent
`
`B.
`The ’197 Patent describes non-porous solid supports with fixed or
`
`immobilized nucleic acids, and systems and arrays comprising such non-porous
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`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
`
`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). Although not required by any of the challenged claims,
`
`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.
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`This Petition will show that the non-porous solid supports and arrays
`
`claimed in the ’197 Patent previously had been disclosed in prior art not considered
`
`during prosecution of the applications leading to the ’197 Patent, for example, in
`
`Fish (Ex. 1006), Noyes (Ex. 1007), VPK (Ex. 1008), Gilham (Ex. 1019), Metzgar
`
`(Ex. 1009), Ramachandran (Ex. 1028) and Sato (Ex. 1034). Ex. 1002 at ¶25. The
`
`prior art shows every limitation of the challenged claims, including the limitations
`
`added to secure allowance of the patent.
`
`Summary of Prosecution History
`
`C.
`The challenged claims in this Petition (“the array claims”) had a very long
`
`prosecution history. The array claims faced many rounds of office action rejections
`
`under 35 U.S.C. § 112, ¶. See, e.g., Ex. 1022, pp. 6-9; Ex. 1014, pp. 4-8. However,
`
`the array claims did not face prior art based rejections. Id. After Patent Owner
`
`submitted multiple expert declarations to overcame the § 112 rejections, the
`
`Examiner allowed the claims. See, e.g., Ex. 1003, pp. 95-126 (providing
`
`voluminous attorney arguments and referring to expert declaration to overcome
`
`§112 rejections); Ex. 1013 at pp. 79-85 (referring to the Waldrop, Stavrianopoulos,
`
`and Kirtikar declarations for overcoming new matter rejections of the array
`
`claims). The Examiner incorrectly failed to recognize prior art that showed arrays
`
`comprising non-porous solid supports with nucleic acids attached in a hybridizable
`
`form thereto.
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`IX. Claim Construction
`In an IPR, an unexpired patent’s claims 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, 17, 19, and 25, 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 European patent application disclosed
`
`non-porous solid supports—despite failing to mention the word “non-porous”—
`
`Patent Owner repeatedly asserted that containers in which reactions take place in
`
`solution, such as the disclosed wells, must be non-porous. 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. Ex.
`
`1026 at pp. 5 and 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.
`
`5), and the Patent Owner admitted that Langer et al. disclosed an in-situ
`
`hybridization method that was performed on “nonporous solid supports that are
`
`transparent or translucent.” (page 7)). And in its Opening Claim Construction Brief
`
`in the related litigations, the Patent Owner noted that “non-porous” is a commonly
`
`understood term—citing the Examiner’s understanding “that glass slides are
`
`‘reasonably interpreted as the commonly utilized non-porous microscope type
`
`slides which are well known in the art.’” Ex. 1023, pp. 8-9 (citing Ex. 1022 (11-26-
`
`2004 Office Action, p. 10)).
`
`Thus, the ordinary and customary meaning of “non-porous solid support”
`
`should apply, which includes conventional laboratory equipment such as microtiter
`
`wells and glass slides. In the related litigations involving the ’197 Patent, the
`
`district court construed the term “non-porous” to mean “having no pores.” Ex.
`
`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
`
`microtiter wells and glass slides, which the Petitioner admits are encompassed by
`
`the claim language “non-porous solid support.”
`
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`“Hybridizable form”
`
`B.
`The term “hybridizable form” is recited in all of the challenged independent
`
`claims as a property of the fixed or immobilized single strand. This term should be
`
`construed as “capable of binding through Watson-Crick base pairing.” This
`
`construction is supported by the specification of the ’197 Patent, which states that
`
`“[p]olynucleotide sequence-based detection techniques are characterized by a
`
`sequence of steps comprising the non-cov