Enzo Life Sciences, Inc. v. Becton, Dickinson and Company

• Court: Court of Appeals for the Federal Circuit
• Decided: August 16, 2019
• Docket: 18-1232
• Status: Unpublished

Opinion

NOTE: This disposition is nonprecedential.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 3 COMPANY

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 VPK 2 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 5 COMPANY

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 7 COMPANY

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 9 COMPANY

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 11 COMPANY

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 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 13 COMPANY

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 15 COMPANY

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