throbber
NOTE: This disposition is nonprecedential.
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`ENZO LIFE SCIENCES, INC.,
`Appellant
`
`v.
`
`BECTON, DICKINSON AND COMPANY,
`Appellee
`
`UNITED STATES,
`Intervenor
`______________________
`
`2018-1232, 2018-1233
`______________________
`
`Appeals from the United States Patent and Trademark
`Office, Patent Trial and Appeal Board in Nos. IPR2016-
`00820, IPR2016-00822.
`______________________
`
`Decided: August 16, 2019
`______________________
`
`JUSTIN P.D. WILCOX, Desmarais LLP, New York, NY,
`argued for appellant. Also represented by KERRI-ANN
`LIMBEEK, KEVIN KENT MCNISH.
`
` THOMAS SAUNDERS, Wilmer Cutler Pickering Hale and
`Dorr LLP, Washington, DC, argued for appellee. Also rep-
`resented by WILLIAM G. MCELWAIN, HEATHER M. PETRUZZI;
`
`

`

`2
`
`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`NANCY SCHROEDER, Los Angeles, CA; OMAR KHAN, New
`York, NY.
`
` DENNIS FAN, Appellate Staff, Civil Division, United
`States Department of Justice, Washington, DC, argued for
`intervenor. Also represented by KATHERINE TWOMEY
`ALLEN, SCOTT R. MCINTOSH, JOSEPH H. HUNT; THOMAS W.
`KRAUSE, JOSEPH MATAL, FARHEENA YASMEEN RASHEED, Of-
`fice of the Solicitor, United States Patent and Trademark
`Office, Alexandria, VA.
` ______________________
`
`Before LOURIE, O’MALLEY, and CHEN, Circuit Judges.
`LOURIE, Circuit Judge.
`Enzo Life Sciences, Inc. appeals from two final written
`decisions of the United States Patent and Trademark Of-
`fice (“PTO”) Patent Trial and Appeal Board (“the Board”)
`holding various claims of U.S. Patent 7,064,197 (“the ’197
`patent”) unpatentable as anticipated or obvious. See Ho-
`logic, Inc. v. Enzo Life Scis., Inc., No. IPR2016-00820, 2017
`WL 4339646 (P.T.A.B. Sept. 28, 2017) (“’820 Decision”); Ho-
`logic, Inc. v. Enzo Life Scis., Inc., No. IPR2016-00822, 2017
`WL 4407743 (P.T.A.B. Oct. 2, 2017) (“’822 Decision”). The
`PTO intervened to defend the constitutionality challenge
`to inter partes review (“IPR”) proceedings as applied to pa-
`tents issued before the enactment of the America Invents
`Act (“AIA”), Pub. L. No. 112-29, 125 Stat. 284 (2011). For
`the following reasons, we affirm.
`BACKGROUND
`Deoxyribonucleic acid (“DNA”) and ribonucleic acid
`(“RNA”) are nucleic acids made of a series of nucleotides.
`A nucleotide is composed of a sugar, a phosphate, and a
`nitrogenous base. DNA has four nitrogenous bases: ade-
`nine (A), guanine (G), cytosine (C), and thymine (T). RNA
`also has the bases adenine (A), guanine (G), and cyto-
`sine (C), but contains uracil (U) instead of thymine (T). A
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`3
`
`polynucleotide refers to multiple nucleotides linked to-
`gether in a chain. Two strands of polynucleotides can bind
`to one another, i.e., hybridize, through hydrogen bonding
`between complementary nucleotides known as Watson-
`Crick base pairing: bases T or U pair with A, and G pairs
`with C. A strand of nucleotides that is not hybridized to
`another strand is said to be single-stranded, while two
`strands hybridized to each other are said to be double-
`stranded.
`Enzo owns the ’197 patent directed to “the detection of
`genetic material by polynucleotide probes.” ’197 patent
`col. 1 ll. 23–24. The invention leverages hybridization
`techniques to detect the presence of an analyte, which may
`be “a DNA or RNA molecule,” “a molecular complex,” or “a
`biological system containing nucleic acids, such as a virus,
`a cell, or group of cells.” Id. col. 1 ll. 39–42. A polynucleo-
`tide probe that is complementary to a target analyte will
`hybridize with it and is thereby used to detect that ana-
`lyte’s presence. See id. col. 2 ll. 37–63. According to the
`invention, the analytes to be detected are “fixed . . . in hy-
`bridizable form to [a] non-porous solid support.” Id. col. 13
`ll. 63–67; see also id. col. 5 ll. 58–60. The specification also
`discloses that a “technique for improving the fixing or uni-
`formity of the plastic surface for fixing DNA involves treat-
`ment of the surface with polylysine.” Id. col. 11 ll. 37–39.
`Independent claim 1 is representative of the claims
`challenged in IPR2016-00820 (“the ’820 IPR”) and inde-
`pendent claim 17 is representative of the claims challenged
`in IPR2016-00822 (“the ’822 IPR”):
`1. A non-porous solid support comprising one or
`more amine(s), hydroxyl(s) or epoxide(s) thereon,
`wherein at least one single-stranded nucleic acid 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).
`Id. col. 13 ll. 63–67 (emphases added).
`
`

`

`4
`
`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`17. An array comprising various single-stranded
`nucleic acids fixed or immobilized in hybridizable
`form to a non-porous solid support.
`Id. col. 15 ll. 51–53 (emphases added).
`Hologic, Inc. filed two petitions for IPR of the ’197 pa-
`tent. During both proceedings, Becton, Dickinson, & Com-
`pany (“Becton”) moved to join as a co-petitioner, and the
`Board granted the motions. See Joinder Order at 2, Ho-
`logic, Inc. v. Enzo Life Scis., Inc., No. IPR2016-00820
`(P.T.A.B. Mar. 27, 2017), Paper No. 32; Joinder Order at 2,
`Hologic, Inc. v. Enzo Life Scis., Inc., No. IPR2016-00822
`(P.T.A.B. Apr. 5, 2017), Paper No. 31. The Board instituted
`trial on all eight grounds of unpatentability across the two
`IPRs, which all rely on Fish1 or VPK2 as the primary refer-
`ence.
`The Board determined that all the challenged claims
`were unpatentable as anticipated by Fish or rendered ob-
`vious by Fish alone or in combination with other prior art
`references. ’820 Decision, 2017 WL 4339646, at *11–15;
`’822 Decision, 2017 WL 4407743, at *10–15. The Board
`next determined that VPK qualified as a prior art refer-
`ence. ’820 Decision, 2017 WL 4339646, at *15–18; ’822 De-
`cision, 2017 WL 4407743, at *15–18. The Board found that
`the ’197 patent could not claim priority from its original
`parent application’s filing date of January 27, 1983,
`
`
`1 Falk Fish & Morris Ziff, A Sensitive Solid Phase
`Microradioimmunoassay for Anti-Double Stranded DNA
`Antibodies, 24 Arthritis and Rheumatism 534–43 (Mar.
`1981), J.A. 1266–75 (“Fish”).
`2 A.C. van Prooijen-Knegt et al., In Situ Hybridiza-
`tion of DNA Sequences in Human Metaphase Chromosomes
`Visualized by an Indirect Fluorescent Immunocytochemical
`Procedure, 141 Experimental Cell Research 397–407 (Oct.
`1982), J.A. 1288–98 (“VPK”).
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`5
`
`because that application did not provide written descrip-
`tion support for the claimed “non-porous solid support.”
`See, e.g., ’197 patent col. 13 l. 63. Instead, the Board deter-
`mined that the ’197 patent could only claim priority from
`the 1983 application’s child continuation-in-part applica-
`tion, which was filed on May 9, 1985. VPK was publicly
`available as of October 1982, more than a year before the
`critical date of May 9, 1985, and thus qualified as prior art.
`See 35 U.S.C. § 102(b) (2006). The Board then concluded
`that all the challenged claims were anticipated by VPK or
`would have been obvious over VPK in combination with
`other prior art references. ’820 Decision, 2017 WL
`4339646, at *19–24; ’822 Decision, 2017 WL 4407743, at
`*20–23.
`Enzo appeals. The PTO intervened pursuant to 35
`U.S.C. § 143 to defend against Enzo’s constitutionality
`challenge to IPRs as applied to the ’197 patent because it
`issued on June 20, 2006, which is before the enactment of
`the AIA in 2011. Enzo argues that constitutes a violation
`of the Fifth Amendment. Before this case was argued, Ho-
`logic moved to withdraw as a party to this appeal, and this
`court granted the motion. See Enzo Life Scis., Inc. v. Bec-
`ton, Dickinson & Co., Nos. 2018-1232, 2018-1233 (Fed. Cir.
`Apr. 25. 2019), ECF No. 74. Becton remains as appellee.
`We have jurisdiction under 28 U.S.C. § 1295(a)(4)(A).
`DISCUSSION
`We review the Board’s legal determinations de novo,
`and the Board’s factual findings underlying those determi-
`nations for substantial evidence. Belden Inc. v. Berk-Tek
`LLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015). A finding is
`supported by substantial evidence if a reasonable mind
`might accept the evidence to support the finding. Consol.
`Edison Co. v. NLRB, 305 U.S. 197, 229 (1938).
`Anticipation is a question of fact that we review for sub-
`stantial evidence. In re Rambus, Inc., 753 F.3d 1253, 1256
`(Fed. Cir. 2014). A prior art document may anticipate a
`
`

`

`6
`
`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`claim if it describes every element of the claimed invention,
`either expressly or inherently. Husky Injection Molding
`Sys. Ltd. v. Athena Automation Ltd., 838 F.3d 1236, 1248
`(Fed. Cir. 2016). Whether there are inherent teachings in
`a prior art reference is a question of fact. See In re Napier,
`55 F.3d 610, 613 (Fed. Cir. 1995).
`Obviousness is a question of law based on underlying
`factual findings, including “the scope and content of the
`prior art, differences between the prior art and the claims
`at issue, the level of ordinary skill in the pertinent art, and
`any objective indicia of non-obviousness.” Randall Mfg. v.
`Rea, 733 F.3d 1355, 1362 (Fed. Cir. 2013) (citing KSR Int’l
`Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007)).
`I. ANTICIPATION BY FISH
`The Board determined that 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 in the ’820 IPR
`and claims 17, 19, 25, 105, 106, 114, 116, 119, 128, 129,
`150, 152, 178, 180, 186, and 187 in the ’822 IPR were an-
`ticipated by Fish. ’820 Decision, 2017 WL 4339646, at *11–
`12; ’822 Decision, 2017 WL 4407743, at *10–11. Fish
`teaches a microradioimmunoassay for detecting antibodies
`that bind to double-stranded DNA (“dsDNA”). See J.A.
`1266. It further notes the use of poly-L-lysine (“PLL”) “to
`facilitate the binding of pure dsDNA to plastic surfaces.”
`Id. Fish also discloses experiments using single-stranded
`DNA (“ssDNA”) in the form of a mixture of synthetic poly-
`mers deoxyadenosine (“poly-dA”) and deoxycytidine (“poly-
`dC”) or “denatured calf thymus DNA.” J.A. 1268.
`All of the challenged independent claims in both the
`’820 IPR and ’822 IPR require the single-stranded nucleic
`acid to be “fixed or immobilized in hybridizable form” (the
`“hybridizable form limitation”). See, e.g., ’197 patent col.
`13 l. 65, col. 15 l. 52. The Board construed “hybridizable
`form” to mean “capable of binding through Watson-Crick
`base pairing,” adopting
`the parties’ agreed-upon
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`7
`
`construction. ’820 Decision, 2017 WL 4339646, at *5 (em-
`phasis added).3 The Board further clarified the construc-
`tion in its final written decisions to mean that “it has bases
`available for base-pairing.” Id. at *6.
`Based on its construction, the Board found that Fish
`disclosed the hybridizable form limitation. The Board
`found that Fish teaches ssDNA bound to the PLL-coated
`wells. See id. at *8. The Board further found that being
`capable of hybridizing is the inherent result of ssDNA be-
`ing fixed to PLL-treated non-porous solid supports. See id.
`at *10–11. The Board rejected Enzo’s argument that Fish
`failed to disclose hybridization and found that “actual hy-
`bridization is not a requirement of any challenged claim.”
`Id. at *10. The claims only recite “hybridizable form,” and
`the Board noted that the parties’ stipulated construction
`required that the single-stranded nucleic acid be “capable
`of binding through Watson-Crick base pairing” and did not
`require “actual hybridization.” Id. (citations omitted). The
`Board thus concluded that the challenged claims were an-
`ticipated by Fish. Id. at *11–12.
`On appeal, Enzo argues that Fish does not disclose nu-
`cleic acid hybridization, but instead describes “binding ra-
`dioactively-labeled antibodies” to dsDNA. Appellant’s Br.
`24 (emphasis omitted). Moreover, Enzo contends, as it did
`before the Board, that the nucleic acids in Fish did not ac-
`tually hybridize in any of the experiments, and thus the
`finding that Fish discloses hybridization lacks substantial
`evidence. According to its expert, Dr. Buck, the fact that a
`single-stranded nucleic acid exists does not mean it is in
`hybridizable form. For example, Dr. Buck testified that “a
`nucleic acid may be ‘restricted by the bonds formed be-
`tween the nucleic acid and the support’ or inhibited by
`
`3 The claim construction discussions of the two
`Board opinions are identical. Thus, citations regarding the
`Board’s claim construction will only be to the ’820 Decision.
`
`

`

`8
`
`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`‘entanglement of the nucleic acid strands themselves,
`which may form loops and coils, called secondary struc-
`tures, restricting the diffusion of other nucleic acid strands
`available for hybridization.’” Id. at 25 (quoting J.A. 3630–
`31 ¶ 95, 5605–06 ¶ 95). Enzo also argues that Dr. Nelson,
`the petitioners’ expert, failed to apply the modified claim
`construction and thus his testimony cannot constitute sub-
`stantial evidence for the Board’s findings.
`Becton responds that the Board correctly found that
`Fish inherently discloses the hybridizable form limitation.
`Relying on Dr. Nelson’s testimony, Becton argues that the
`positively-charged amines on the surface of the solid sup-
`port coated with PLL, as disclosed in Fish, will bond with
`the negatively-charged phosphate groups in the DNA back-
`bone leaving the bases free to hybridize. Becton criticizes
`Enzo for “deliberately sabotaging the experiment” in order
`to describe a situation where someone using Fish’s PLL
`binding chemistry would not create a hybridizable single-
`stranded nucleic acid. Appellee’s Br. 37. Becton contends
`that inherency cannot be defeated by “interfer[ing] with
`the natural result of a process.” Id. at 38.
`We agree with Becton that Fish’s disclosure of a ssDNA
`bound to a solid support coated with PLL inherently dis-
`closes that the single-stranded nucleic acid is in hybridiza-
`ble form. “A reference includes an inherent characteristic
`if that characteristic is the ‘natural result’ flowing from the
`reference’s explicitly explicated limitations.” Eli Lilly &
`Co. v. Barr Labs., Inc., 251 F.3d 955, 970 (Fed. Cir. 2001)
`(quoting Cont’l Can Co. USA, Inc. v. Monsanto Co., 948
`F.2d 1264, 1269 (Fed. Cir. 1991)).
`Here, substantial evidence supports the Board’s find-
`ing that the single-stranded nucleic acid of Fish is inher-
`ently hybridizable. The Board reasonably relied on
`testimony from both experts that a characteristic of single-
`stranded nucleic acids is that their bases are available to
`pair with complementary bases through Watson-Crick
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`9
`
`pairing. See ’820 Decision, 2017 WL 4339646, at *11 (citing
`J.A. 891 ¶ 64); ’822 Decision, 2017 WL 4407743, at *9; see
`also J.A. 874–75 ¶ 24, 891 ¶ 64 (Dr. Nelson’s testimony);
`J.A. 3705–06 ¶ 189 (Dr. Buck’s testimony). That is what a
`single-stranded nucleic acid does in the presence of comple-
`mentary bases. Unless purposely prohibited, the binding
`capability is inherent in the nature of a single-stranded nu-
`cleic acid. The Board’s finding that Fish’s disclosure of a
`ssDNA fixed to a PLL-treated support inherently teaches
`the hybridizable form limitation is thus based on substan-
`tial evidence.
`Enzo also argues that in the ’822 IPR, the Board erred
`in finding that Fish disclosed an “array” of “single-stranded
`nucleic acids.” See, e.g., ’197 patent col. 15 ll. 51–53. All of
`the challenged independent claims in the ’822 IPR recite
`an “array” of “single-stranded nucleic acids.” See, e.g., id.
`The Board construed “array” to include “an orderly group-
`ing or arrangement of wells or depressions.” ’822 Decision,
`2017 WL 4407743, at *4. The Board then found that Fish
`teaches this limitation because “it discloses microtitration
`trays having wells of ssDNA.” Id. at *7 (citing J.A. 1268).
`Enzo contends that Fish fails to disclose an “array” of
`“single-stranded nucleic acids.” See, e.g., ’197 patent col. 15
`ll. 51–53 (emphasis added). According to Enzo, the Board
`erred in reading the term “array” in isolation from “single-
`stranded nucleic acids,” and thus erred in finding that a
`container with wells or depressions without any nucleic ac-
`ids would meet the claim language.
`Becton responds, and we agree, that the Board’s find-
`ing was supported by substantial evidence. Fish describes
`supports having rows of wells coated with ssDNA. See J.A.
`1268. The Board also credited Dr. Nelson’s testimony that
`Table 1 in Fish provides evidence that the ssDNA bound
`effectively to the PLL-coated wells of the microtitration
`tray. ’822 Decision, 2017 WL 4407743, at *7 (citing J.A.
`1268). That constitutes substantial evidence to support the
`
`

`

`10
`
`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`Board’s finding that Fish teaches an “array” of “single-
`stranded nucleic acids.” See, e.g., ’197 patent col. 15 ll. 51–
`53.
`
`Enzo does not raise any arguments with respect to any
`other claim limitation, nor does it separately argue the de-
`pendent claims. Thus, the dependent claims stand or fall
`together with the independent claims. See In re Kaslow,
`707 F.2d 1366, 1376 (Fed. Cir. 1983). We therefore con-
`clude that the Board did not err in finding that Fish antic-
`ipates 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 in the ’820 IPR and claims 17, 19, 25,
`105, 106, 114, 116, 119, 128, 129, 150, 152, 178, 180, 186,
`and 187 in the ’822 IPR.
`II. OBVIOUSNESS GROUNDS BASED ON FISH
`The Board determined that claims 31, 64, 68, 101, 192,
`and 195 in the ’820 IPR and claims 130, 131, 151, and 154
`in the ’822 IPR would have been obvious over Fish. ’820
`Decision, 2017 WL 4339646, at *12–14; ’822 Decision, 2017
`WL 4407743, at *11–14. Those claims add one of the fol-
`lowing limitations: “wherein said nucleic acid comprises a
`nucleic acid sequence complementary to a nucleic acid se-
`quence of interest sought to be identified, quantified or se-
`quenced,” see, e.g., ’197 patent col. 17 ll. 1–4; or “wherein
`said nucleic acid is RNA,” see, e.g., id. col. 18 ll. 38–39; or
`“wherein said nucleic acids comprise a gene sequence or
`pathogen sequence,” id. col. 22 ll. 42–43. Enzo does not
`separately argue the challenged dependent claims and re-
`lies on the arguments it raised for anticipation by Fish.
`Thus, for the same reasons that Fish anticipates the afore-
`mentioned claims, we also hold that Fish renders obvious
`claims 31, 64, 68, 101, 192, and 195 in the ’820 IPR and
`claims 130, 131, 151, and 154 in the ’822 IPR.
`The Board next determined that claims 38, 78, and 218
`in the ’820 IPR and claims 113 and 185 in the ’822 IPR
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`11
`
`would have been obvious over Fish and Gilham;4 and
`claims 120 and 189 in the ’822 IPR would have been obvi-
`ous over Fish, U.S. Patent 3,572,892 (“Metzgar”), and
`Sato.5 Enzo argues that the Board’s findings of a motiva-
`tion to combine Fish and Gilham, and Fish, Metzgar, and
`Sato, are not based on substantial evidence. We take the
`arguments asserted for each ground in turn.
`A. Obviousness over Fish and Gilham
`The Board determined that claims 38, 78, and 218 in
`the ’820 IPR and claims 113 and 185 in the ’822 IPR would
`have been obvious over Fish and Gilham. ’820 Decision,
`2017 WL 4339646, at *14–15; ’822 Decision, 2017 WL
`4407743, at *14–15. The challenged claims add the limita-
`tion “wherein said fixation or immobilization to said non-
`porous solid support is covalent.” See, e.g., ’197 patent col.
`17 ll. 24–26 (emphasis added). Gilham teaches a method
`of covalently binding RNA to cellulous supports. See J.A.
`1592–93. The Board found that a person of ordinary skill
`in the art would have been motivated, with a reasonable
`expectation of success, to apply Gilham’s method of cova-
`lently binding RNA to Fish’s non-porous supports, such as
`the microtitration plates, “because covalent binding pro-
`vides a stronger linkage between the immobilized nucleic
`acids and the solid substrate.” ’820 Decision, 2017 WL
`4339646, at *15 (internal citation omitted).6
`
`
`4 P.T. Gilham, Immobilized Polynucleotides and Nu-
`cleic Acids, Immobilized Biochemicals and Affinity Chro-
`matography 173–85 (1974), J.A. 1592–1604 (“Gilham”).
`5 Chikako Sato et al., Cell Surface Charge and Cell
`Division in Escherichia coli after X Irradiation, 87 Radia-
`tion Research 646–56 (1981), J.A. 4422–32 (“Sato”).
`6 The analyses of Fish and Gilham are identical in
`the two Board opinions. Thus, citations will only be to the
`’820 Decision.
`
`

`

`12
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`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`Enzo argues that the Board failed to identify why a per-
`son of ordinary skill would have been motivated to use the
`covalent binding method for RNA in Gilham with the pro-
`cedures for using DNA of PLL-coated plates to detect anti-
`bodies described in Fish. Moreover, according to Enzo, not
`only was there insufficient motivation to combine, but
`there would not have been an expectation of success. Enzo
`contends that Gilham teaches away from the use of non-
`porous supports like those in Fish, and that Gilham’s cova-
`lent binding would likely negatively affect the nucleic
`acid’s ability to hybridize.
`Becton responds that the Board’s finding of a motiva-
`tion to combine Fish and Gilham was supported by sub-
`stantial evidence. We agree. Dr. Nelson, whom the Board
`credited, explained that both Fish and Gilham disclose nu-
`cleic acids bound to solid support surfaces with amine
`groups. See id. at *13–14. The Board then found that a
`person of ordinary skill in the art would have been moti-
`vated to use the covalent binding from Gilham on Fish’s
`non-porous solid supports. See id. at *15. We also agree
`with Becton that Enzo’s teaching away arguments improp-
`erly attack the references individually. See In re Merck &
`Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (“Non-obvious-
`ness cannot be established by attacking references individ-
`ually where the rejection is based upon the teachings of a
`combination of references.”). However, as the Board deter-
`mined, it is the combined teachings of Gilham’s chemistry
`for binding RNA in hybridizable form and Fish’s methods
`of attaching nucleic acids to non-porous supports that ren-
`der the claims obvious. See ’820 Decision, 2017 WL
`4339646, at *15. Accordingly, the Board did not err in hold-
`ing that claims 38, 78, and 218 in the ’820 IPR and claims
`113 and 185 in the ’822 IPR would have been obvious over
`Fish and Gilham.
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
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`13
`
`B. Obviousness over Fish, Metzgar, and Sato
`The Board determined that claims 120 and 189 in the
`’822 IPR would have been obvious over Fish, Metzgar, and
`Sato. ’822 Decision, 2017 WL 4407743, at *13–14. The
`challenged claims add the limitation “wherein said non-po-
`rous solid support comprises one or more hydroxyls.” See,
`e.g., ’197 patent col. 21 ll. 10–12 (emphasis added).
`Metzgar teaches a “multiple well tissue culture microscope
`slide” where the microscope slide is “glass or other trans-
`parent material.” Metzgar col. 1 l. 2, col. 2 ll. 28–29. Sato
`discloses treating glass slides with PLL. See J.A. 4423. Dr.
`Nelson testified that “glass necessarily includes hydroxyl
`groups.” ’822 Decision, 2017 WL 4407743, at *14 (citing
`J.A. 5789 ¶ 83 (“The glass slides of . . . Metzgar necessarily
`include hydroxyl groups, because that is a known property
`of glass.”)). The Board determined, based on Dr. Nelson’s
`testimony, that a person of ordinary skill in the art would
`have been motivated to use the glass trays from Metzgar
`“as an alternative to Fish’s polyvinyl trays.” Id. (citing J.A.
`5789 ¶ 83). In combination with Sato’s teaching of treating
`glass slides with PLL, the Board concluded that the chal-
`lenged claims would have been obvious over Fish, Metzgar,
`and Sato. Id.
`Enzo argues that the Board failed to identify why a per-
`son of ordinary skill in the art would have been motivated
`to substitute glass plates for the polyvinyl microtitration
`trays disclosed in Fish. According to Enzo, the Board erred
`in failing to credit Dr. Buck’s uncontested testimony that a
`person of ordinary skill would not combine those references
`because they would not work for their intended purposes.
`Becton responds that substantial evidence supported
`the Board’s finding of a motivation to combine Fish,
`Metzgar, and Sato, and we agree. The Board found that
`glass slides having wells or depressions were well-known
`at the time of the invention. See id. The Board further
`found, based on Dr. Nelson’s testimony, that a person of
`
`

`

`14
`
`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`ordinary skill in the art would have been motivated to im-
`mobilize nucleic acids using the methods described in Fish
`on the glass slides disclosed in Metzgar. See id. Addition-
`ally, the Board found that Sato teaches “treatment of glass
`slides with PLL prior to fixing cells on the slides.” Id. The
`Board ultimately credited Dr. Nelson’s testimony that a
`person of ordinary skill in the art would have been moti-
`vated to perform the nucleic acid immobilization procedure
`disclosed in Fish on the glass slides in Metzgar treated
`with PLL as disclosed in Sato. Id. The Board’s finding of
`a motivation to combine was thus based on substantial ev-
`idence. Accordingly, the Board did not err in determining
`that claims 120 and 189 in the ’822 IPR would have been
`obvious over Fish, Metzgar, and Sato.
`In conclusion, we determine that the Board did not err
`in holding that claims 1, 6, 8, 9, 12–17, 19, 25, 27, 31–34,
`38, 41, 61–64, 68–70, 72–74, 78, 79, 100, 101, 105, 106, 113,
`114, 116, 119, 120, 128–131, 150–152, 154, 178, 180, 185–
`187, 189, 191–195, 212, 213, 218, 219, 222, 225–227, 230,
`233, and 236 of the ’197 patent are invalid as anticipated
`by Fish or obvious over Fish alone or in combination with
`other prior art references.
`III. OTHER ISSUES
`Enzo argues that the Board erred in finding that VPK
`qualifies as prior art, and thus the claims are not unpatent-
`able as anticipated or obvious over grounds that include
`VPK. Because we have determined that the Board did not
`err in concluding that all of the challenged claims are un-
`patentable on grounds based on Fish, we need not reach
`the arguments involving VPK. See Oral Arg. at 12:14–
`12:49, 25:58–26:11, Enzo Life Scis., Inc. v. Becton, Dickin-
`son & Co., Nos. 2018-1232, 2018-1233 (Fed. Cir. July 9,
`2019), http://oralarguments.cafc.uscourts.gov/default.aspx
`?fl=2018-1232.mp3.
`Enzo also argues that the IPR process as applied retro-
`actively to patents that issued before the enactment of the
`
`

`

`ENZO LIFE SCIENCES, INC. v. BECTON, DICKINSON AND
`COMPANY
`
`15
`
`AIA violates the Fifth Amendment. We recently addressed
`this issue in Celgene Corp. v. Peter, No. 18-1167, 2019 WL
`3418549, at *12–16 (Fed. Cir. July 30, 2019), which is now
`precedent that governs this case. Celgene held that “retro-
`active application of IPR proceedings to pre-AIA patents is
`not an unconstitutional taking under the Fifth Amend-
`ment.” Id. at *16. Accordingly, we hold that the retroactive
`application of IPR proceedings to the ’197 patent, which is-
`sued before the enactment of the AIA, is not an unconstitu-
`tional taking under the Fifth Amendment.
`CONCLUSION
`We have considered Enzo’s remaining arguments but
`find them unpersuasive. For the foregoing reasons, we af-
`firm the decisions of the Board.
`AFFIRMED
`
`

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