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` Paper No. 33
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` Filed: March 3, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BUTAMAXTM ADVANCED BIOFUELS LLC,
`Petitioner,
`
`v.
`
`GEVO, INC.,
`Patent Owner.
`____________
`
`Case IPR2013-00539
`Patent 8,273,565 B2
`____________
`
`
`Before RAMA G. ELLURU, CHRISTOPHER L. CRUMBLEY, and
`KERRY BEGLEY, Administrative Patent Judges.
`
`BEGLEY, Administrative Patent Judge.
`
`
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`
`
`ButamaxTM Advanced Biofuels LLC (“Petitioner”) filed a Petition
`
`requesting inter partes review of claims 1–19 of U.S. Patent No. 8,273,565
`
`B2 (Ex. 1001, “the ’565 patent”). Paper 4 (“Pet.”). Pursuant to 35 U.S.C.
`
`§ 314(a), we determined the Petition showed a reasonable likelihood that
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`Petitioner would prevail in establishing the unpatentability of claims 1–9 and
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`11–19 of the ’565 patent, and instituted an inter partes review of these
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`
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`Patent 8,273,565 B2
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`claims on certain asserted grounds of unpatentability. Paper 9 (“Inst. Dec.”).
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`We, however, did not institute review of claim 10 of the ’565 patent,
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`because we determined the Petition did not show a reasonable likelihood that
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`Petitioner would prevail in establishing the claim to be unpatentable. Id. at
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`27–29.
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`Patent Owner Gevo, Inc. (“Patent Owner”) then filed a Patent Owner
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`Response. Paper 19 (“PO Resp.”). Petitioner filed a Reply to Patent
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`Owner’s Response. Paper 21 (“Reply”).
`
`An oral hearing was held on October 28, 2014, pursuant to a request
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`by Petitioner. Paper 32 (“Tr.”); Petitioner Butamax’s Request for Oral
`
`Argument (Paper 23); Order – Trial Hearing (Paper 24), at 1. During the
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`oral hearing, Petitioner presented argument; Patent Owner rested on its
`
`arguments in the Patent Owner Response. Tr. 40:3–13; see id. at 39:7–
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`42:18; Order – Conduct of the Proceeding (Paper 25).
`
`We issue this Final Written Decision pursuant to 35 U.S.C. § 318(a)
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`and 37 C.F.R. § 42.73. For the reasons that follow, we determine Petitioner
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`has shown by a preponderance of the evidence that claims 1–9 and 11–19 of
`
`the ’565 patent are unpatentable.
`
`I. BACKGROUND
`
`A. THE ’565 PATENT
`
`The ’565 patent, titled “Methods of Increasing Dihydroxy Acid
`
`Dehydratase Activity to Improve Production of Fuels, Chemicals, and
`
`Amino Acids,” is directed to recombinant yeast microorganisms with
`
`increased activity of dihydroxy acid dehydratase (“DHAD”). Ex. 1001,
`
`[57], 1:29–2:25. DHAD is an enzyme that catalyzes steps in various
`
`biosynthetic pathways that produce metabolites, such as isobutanol, a
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`2
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`common fuel additive. Id. at [57], 1:46–66, Fig. 1. Increased DHAD
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`activity is favorable for producing these metabolites. Id. at 1:65–2:20,
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`24:31–33. The patent also discloses methods of producing such metabolites
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`by cultivating the disclosed recombinant microorganisms in a culture
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`medium containing a carbon source feedstock. Id. at [57], 8:55–63.
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`The specification of the ’565 patent discloses recombinant
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`microorganisms with increased DHAD activity resulting from alterations in
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`the regulation, expression, or activity of either or both the GRX3 and GRX4
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`genes, which encode the proteins monothiol glutaredoxin-3 (“Grx3”) and
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`monothiol glutaredoxin-4 (“Grx4”), respectively. Id. at 24:36–50; see id. at
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`23:30–57, 24:1–30. For example, in one embodiment, the Grx3 protein, the
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`Grx4 protein, or both the Grx3 and Grx4 proteins are “deleted or
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`attenuated.” Id. at 24:9–11. The specification also discloses recombinant
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`microorganisms with improved DHAD activity resulting from
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`overexpression of either or both the transcriptional activator genes AFT1 and
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`AFT2, which encode activator of ferrous transport (“Aft”) proteins, Aft1 and
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`Aft2, respectively. Id. at 2:9–25, 4:14–26, 15:49–54. The DHAD in these
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`embodiments may be localized in either the cytosol or the mitochondria of
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`the microorganisms. Id. at 3:30–46, 16:33–34, 24:36–45. Further, the
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`recombinant microorganisms may be one of various disclosed yeast genera
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`and species, including Saccharomyces cerevisiae. See id. at 7:49–8:54.
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`B. ILLUSTRATIVE CLAIM
`
`Claim 1, the only independent claim of the ’565 patent, is illustrative
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`of the challenged claims:
`
`1. A recombinant yeast microorganism comprising a
`recombinantly overexpressed polynucleotide encoding a
`dihydroxy acid dehydratase (DHAD),
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`
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`3
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`wherein said recombinant yeast microorganism is
`engineered to comprise at least one inactivated monothiol
`glutaredoxin selected from the group consisting of
`monothiol glutaredoxin-3 (GRX3) and monothiol
`glutaredoxin-4 (GRX4),
`
`and wherein said inactivated monothiol glutaredoxin results
`from the deletion of one or more nucleotides of an
`endogenous gene encoding said monothiol glutaredoxin, the
`insertion of one or more nucleotides into an endogenous
`gene encoding said monothiol glutaredoxin, or combinations
`thereof.
`
`Id. at 91:15–26 (line breaks added).
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`C. INSTITUTED GROUNDS OF UNPATENTABILITY
`
`We instituted inter partes review of the ’565 patent on the following
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`grounds of unpatentability asserted in the Petition. Inst. Dec. 29.
`
`Basis
`Claim[s]
`1–4, 6–8, and 11–19 § 102(e) Flint
`1–4, 6–8, 11, 13, 14,
`§ 103(a) Anthony, Puig, and Ojeda
`and 16–19
`5
`9
`
`§ 103(a) Anthony, Puig, Ojeda, and Li
`§ 103(a) Anthony, Puig, Ojeda, and van Maris
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`Reference[s]
`
`These instituted grounds rely on the following prior art references:
`
`Anthony US 2010/0081179 A1
`Li
`US 2009/0163376 A1
`Flint
`WO 2011/103300 A2
`
`Apr. 1, 2010
`June 25, 2009
`Aug. 25, 2011
`
`Ex. 1005
`Ex. 1015
`Ex. 1003
`
`
`Antonius J. A. van Maris et al., Directed Evolution of Pyruvate
`Decarboxylase-Negative Saccharomyces cerevisiae, Yielding a C2-
`Independent, Glucose-Tolerant, and Pyruvate-Hyperproducing Yeast, 70
`APPLIED & ENVTL. MICROBIOLOGY 159 (2004). (Ex. 1008, “van Maris.”)
`
`Sergi Puig et al., Coordinated Remodeling of Cellular Metabolism During
`Iron Deficiency Through Targeted mRNA Degradation, 120 CELL 99 (2005).
`(Ex. 1006, “Puig.”)
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`Luis Ojeda et al., Role of Glutaredoxin-3 and Glutaredoxin-4 in the Iron
`Regulation of the Aft1 Transcriptional Activator in Saccharomyces
`cerevisiae, 281 J. BIOLOGICAL CHEMISTRY 17661 (2006). (Ex. 1007,
`“Ojeda.”)
`
`II. ANALYSIS
`A. LEVEL OF ORDINARY SKILL IN THE ART
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`
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`We begin our analysis by addressing the level of ordinary skill in the
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`art, which is relevant to the governing standards we apply in the remainder
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`of our analysis. Petitioner proposes a standard for one of ordinary skill in
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`the art. Pet. 6; see Ex. 1002 (Decl. of Dennis J. Thiele, Ph.D.) ¶ 17. Patent
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`Owner has not contested this proposal or proffered an alternative standard.
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`We adopt Petitioner’s proposed standard and, therefore, determine that one
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`of ordinary skill in the art would have had either: (1) “a Ph.D. in the life
`
`sciences or a similar related discipline, and . . . familiarity, training, and
`
`experience in molecular biology, microbial genetics and/or microbial
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`metabolism,” or (2) “a scientific background such as a Bachelor’s degree in
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`the life sciences (e.g., biology, microbiology, molecular biology or
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`biochemistry) or a similar related discipline, and . . . substantial familiarity,
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`training, and experience in molecular biology, microbial genetics and/or
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`microbial metabolism.” Pet. 6; see Ex. 1002 ¶ 17.
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`B. CLAIM INTERPRETATION
`
`We next address the meaning of the claims. The Board interprets
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`claims using the “broadest reasonable construction in light of the
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`specification of the patent in which [they] appear[].” 37 C.F.R. § 42.100(b);
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`see In re Cuozzo Speed Techs., LLC, No. 2014-1301, 2015 WL 448667, at
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`*5–*8 (Fed. Cir. Feb. 4, 2015). We presume a claim term carries its
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`“ordinary and customary meaning,” which is “the meaning that the term
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`would have to a person of ordinary skill in the art in question” at the time of
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`the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
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`2007). This presumption, however, is rebutted when the patentee acts as a
`
`lexicographer by giving the term a particular meaning in the specification
`
`with “reasonable clarity, deliberateness, and precision.” In re Paulsen, 30
`
`F.3d 1475, 1480 (Fed. Cir. 1994).
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`1. “INACTIVATED”
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`Petitioner asserts that “inactivated,” as used in the following limitation
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`of claim 1, “said recombinant yeast microorganism is engineered to
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`comprise at least one inactivated monothiol glutaredoxin selected from the
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`group consisting of monothiol glutaredoxin-3 (GRX3) and monothiol
`
`glutaredoxin-4 (GRX4),” Ex. 1001, 91:17–21 (emphasis added), “should be
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`construed to mean that the GRX3 and/or GRX4 protein lacks all activity and
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`excludes GRX3 and/or GRX4 proteins having reduced, attenuated or partial
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`activities.” Pet. 7. Petitioner supports its argument with statements in an
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`Examiner-Initiated Interview Summary in the prosecution history of the
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`’565 patent in which Patent Owner “noted that the meaning of ‘inactivate’ is
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`to render inactive so that GRX3 and GRX4 protein have no activity thereof,”
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`and the Patent Examiner “agree[d].” Id. at 7; Ex. 1012, Examiner-Initiated
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`Interview Summary (May 17, 2012). Patent Owner has not responded to
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`Petitioner’s assertions regarding the meaning of “inactivated” or proposed a
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`construction for the term. See generally PO Resp.
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`The plain and ordinary meaning of “inactivated” is having destroyed
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`biologic activity; chemically or biologically inert; non-functional. See
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`Ex. 3005 (The American Heritage Medical Dictionary 402 (Rev. ed. 2007))
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`(defining “inactivate” as “[t]o render nonfunctional”); Ex. 3006 (Stedman’s
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`6
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`Medical Dictionary 959 (28th ed., Lippincott Williams & Wilkins 2006))
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`(defining “inactivate” as “[t]o destroy the biologic activity or the effects of
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`an agent or substance”); Ex. 3007 (Merriam-Webster’s Collegiate
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`Dictionary 584 (10th ed. 2000)) (defining “inactivate” as “to make inactive,”
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`and “inactive” as “chemically” or “biologically inert”); Ex. 3008 (Dictionary
`
`of Science and Technology 1092 (Christopher Morris, ed. 1992)) (defining
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`“inactivate” as “to render inactive; destroy the activity of”). This customary
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`meaning, thus, requires a lack of all activity or functionality.
`
`The usage of “inactivated” and related terms in the specification of the
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`’565 patent neither elucidates the meaning of the term nor indicates any
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`deviation from its ordinary and customary meaning. Dependent claims 9
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`and 10 recite the term “inactivate” in a manner similar to “inactivated” in
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`claim 1: “said recombinant yeast microorganism is further engineered to
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`inactivate one or more endogenous pyruvate decarboxylase (PDC)”
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`(claim 9) and “glycerol-3-phosphate dehydrogenase (GPD)” (claim 10).
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`Ex. 1001, 91:58–65 (emphasis added). These claims, therefore, offer no
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`further clarity regarding the meaning of the term. Likewise, references to
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`the term in other portions of the specification do not define or otherwise
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`explicate its meaning. Upon review of the record, we are not persuaded that
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`the inventors of the ’565 patent acted as their own lexicographer to alter the
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`ordinary and customary meaning of the term “inactivated.”
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`Accordingly, to the extent Petitioner’s proposed construction of
`
`“inactivated” requires a “lack[ of] all activity,” we conclude that it is
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`consistent with the plain and ordinary meaning of the term as well as its
`
`usage in the ’565 patent specification. Pet. 7. We, however, reject the
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`remainder of Petitioner’s proffered construction, “exclud[ing] GRX3 and/or
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`7
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`GRX4 proteins having reduced, attenuated or partial activities,” because it is
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`directed to the scope of claim 1, rather than the meaning of the term
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`“inactivated.” Id.
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`For these reasons, we construed “inactivated” to mean lacking all
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`activity or functionality in our Decision to Institute. Inst. Dec. 8–10.
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`Neither party has challenged this construction. See generally PO Resp.;
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`Reply. Having considered whether this construction should be changed in
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`light of the evidence introduced during trial, we are not persuaded any
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`modification is necessary. Therefore, we maintain our construction of
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`“inactivated” as lacking all activity or functionality.
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`2. OTHER CLAIM TERMS
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`Petitioner also proposes a construction for the final limitation of claim
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`1, asserting that the recited inserted or deleted nucleotides could not occur in
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`“regulatory regions associated with the endogenous genes.” Pet. 8–11. In
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`our Decision to Institute, we determined that we need not address
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`Petitioner’s proposed construction, because whether the inserted or deleted
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`nucleotides can occur in regulatory regions does not impact Petitioner’s
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`asserted grounds of unpatentability. Inst. Dec. 10–11. Neither party has
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`challenged this determination. See Reply 1; see generally PO Resp. Having
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`considered the issue in light of the evidence adduced during trial, we are not
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`persuaded that any modification of our determination is necessary.1
`
`
`1 The Petition also argues that claim 1 encompasses at least the yeast genera
`and species recited in dependent claims 17 and 18, and at least DHAD
`localized in either the cytosol or the mitochondria, as recited in dependent
`claims 11 and 12, respectively. Pet. 9–10. Although we agreed with
`Petitioner in our Decision to Institute, this interpretation is not necessary to
`our final decision. See Inst. Dec. 11–12; Pet. 24–25; infra n.5.
`
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`C. INSTITUTED GROUNDS OF UNPATENTABILITY
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`We turn to the merits of the instituted grounds of unpatentability.
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`1. ANTICIPATION BY FLINT — CLAIMS 1–4, 6–8, AND 11–19
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`We begin with the instituted ground asserting that claims 1–4, 6–8,
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`and 11–19 of the ’565 patent are unpatentable under 35 U.S.C. § 102(e)2 as
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`anticipated by Flint. Pet. 12–29; Inst. Dec. 12–18, 29. Flint, PCT
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`Application No. WO 2011/103300 A2, was filed on February 17, 2011, and
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`claims priority to U.S. Provisional Application No. 61/305,333 (“’333
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`provisional” or “Flint ’333 provisional”), filed on February 17, 2010.
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`Ex. 1003, [10], [22], [30], [43]. Therefore, Flint’s earliest claimed effective
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`filing date is February 17, 2010.
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`The ’565 patent was filed on September 27, 2011 as a divisional of
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`U.S. Application Serial Nos. 13/228,342, filed September 8, 2011, and
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`12/953,884, filed November 24, 2010. Ex. 1001, [22], [62], 1:9–12. The
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`’565 patent further claims priority to two provisional applications: U.S.
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`Provisional Application Serial Nos. 61/350,209 (“’209 provisional”), filed
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`June 1, 2010, and 61/263,952 (“’952 provisional”), filed November 24,
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`2009. Id. at [60], 1:12–17.
`
`Thus, Flint—with the benefit of the filing date of the ’333 Flint
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`provisional (February 17, 2010)—is prior art to the ’565 patent under
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`§ 102(e) unless the ’565 patent is entitled to the benefit of the filing date of
`
`the ’952 provisional (November 24, 2009). See 35 U.S.C. § 102(e); Pet. 12.
`
`
`2 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29, 125
`Stat. 284 (2011), revised 35 U.S.C. §§ 102–103, effective March 16, 2013.
`Because the ’565 patent has an effective filing date before March 16, 2013,
`our references and citations to §§ 102–103 in this decision are to their pre-
`AIA version.
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`Accordingly, in addition to arguing that Flint and the ’333 provisional
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`disclose each limitation of claims 1–4, 6–8, and 11–19 of the ’565 patent,
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`the Petition further contends that the ’565 patent claims are not entitled to
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`the benefit of the filing date of either the ’952 provisional or the
`
`’209 provisional, because neither provides written description support for
`
`claim 1, the sole independent claim, of the ’565 patent. Pet. 12–29.
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`In the Response, Patent Owner disputes Petitioner’s assertion that
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`Flint is prior art to the ’565 patent, arguing that the ’565 patent is entitled to
`
`the benefit of the filing date of the ’952 provisional, because both the ’952
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`and ’209 provisionals provide written description support for the ’565 patent
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`claims. PO Resp. 2–3, 5–15. Patent Owner, however, does not contest that
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`Flint and the ’333 provisional disclose each limitation of claims 1–4, 6–8,
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`and 11–19 of the ’565 patent. See id. at 2–3, 15.
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`We consider first whether Flint is prior art to the ’565 patent, then
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`whether Flint’s disclosure is anticipatory.
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`a. PRIOR ART STATUS OF FLINT
`
`In this inter partes review, Petitioner has the burden of persuasion to
`
`establish unpatentability—including “all issues relating to the status of
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`[Flint] as prior art,” Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1576–78
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`(Fed. Cir. 1996)—by a “preponderance of the evidence,” 35 U.S.C. § 316(e).
`
`This burden of persuasion remains with Petitioner, while the burden of
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`production—the burden to come forward with evidence—shifts between the
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`parties. See Tech. Licensing Corp. v. Videotek, Inc., 545 F.3d 1316, 1327–
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`29 (Fed. Cir. 2008); Mahurkar, 79 F.3d at 1576–77; Corning Inc. v. DSM IP
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`Assets B.V., Case IPR2013-00053, slip op. at 6–8 (PTAB May 1, 2014)
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`(Paper 66) (“[T]hough the patent owner bears the burden of production in
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`antedating a reference, the burden of persuasion to prove unpatentability . . .
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`remains with the petitioner.”). Now, “with all of the evidence from both
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`sides before [us]”—the burden of production having shifted back and forth
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`between the parties—Petitioner bears the ultimate burden of persuasion to
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`establish by a preponderance of the evidence that Flint is prior art to the
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`’565 patent, including that the ’565 patent is not entitled to the benefit of the
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`earlier filing date of the ’952 provisional. Tech. Licensing, 545 F.3d at
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`1327–29; Mahurkar, 79 F.3d at 1578. We determine that Petitioner has met
`
`its burden, as we explain below.
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`i. Written Description Support for the ’565 Patent Claims in the
`’952 and ’209 Provisionals
`
`Petitioner argues that claim 1 of the ’565 patent, along with its
`
`dependent claims, is not entitled to the benefit of the filing date of either the
`
`’952 or ’209 provisional based on a lack of written description support for
`
`the following limitations of the claim:
`
`wherein said recombinant yeast microorganism is
`engineered to comprise at least one inactivated monothiol
`glutaredoxin selected from the group consisting of
`monothiol glutaredoxin-3 (GRX3) and monothiol
`glutaredoxin-4 (GRX4),
`
`and wherein said inactivated monothiol glutaredoxin results
`from the deletion of one or more nucleotides of an
`endogenous gene encoding said monothiol glutaredoxin, the
`insertion of one or more nucleotides into an endogenous
`gene encoding said monothiol glutaredoxin, or combinations
`thereof.
`
`Pet. 12–24; Ex. 1001, 91:15–26. Petitioner, with supporting testimony from
`
`its expert, Dr. Dennis J. Thiele, asserts that the provisionals describe, at best,
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`only complete deletion of endogenous GRX3 and GRX4 genes. Pet. 17–24;
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`Ex. 1002 ¶¶ 29–49. According to Petitioner, neither provisional provides
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`11
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`precise definitions—such as the type, location, or size—of the insertions,
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`deletions, or insertion and deletions of nucleotides in these genes that would
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`result in “inactivated” Grx3 and Grx4 proteins. Pet. 17–24; Ex. 1002 ¶¶ 29–
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`49. Petitioner, therefore, urges that the “’952 and ’209 provisional
`
`applications fail to describe adequately the full scope of the broadly claimed
`
`deletions, insertions, or combinations of deletions and insertions in the
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`endogenous GRX3 and GRX4 genes” encompassed by claim 1 of the
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`’565 patent. Pet. 20. In response, Patent Owner “directs [our] attention” to
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`a list of disclosures in the ’952 and ’209 provisionals, which Patent Owner
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`argues demonstrates that the inventors were in possession of the full scope
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`of claimed insertions and deletions of nucleotides in the GRX3 and GRX4
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`genes as of the filing date of each provisional. PO Resp. 7–15. Patent
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`Owner also argues that one of ordinary skill would have been familiar with
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`gene deletions and insertions as techniques for “inactivating a gene” and,
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`thus, Petitioner’s arguments overlook that it is not necessary to disclose in
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`detail what was well known in the art. Id. at 13–15.
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`A claim in a later-filed patent application is entitled to the benefit of
`
`the filing date of an earlier-filed provisional application only if the
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`provisional application, and all applications in the chain leading back to the
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`provisional application, satisfy the written description requirement of
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`35 U.S.C. § 112 for the invention claimed in the later-filed application. New
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`Railhead Mfg., L.L.C. v. Vermeer Mfg. Co., 298 F.3d 1290, 1294–97 (Fed.
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`Cir. 2002); see 35 U.S.C. §§ 119(e)(1), 120; Hollmer v. Harari, 681 F.3d
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`1351, 1355 (Fed. Cir. 2012). This requirement prevents an inventor from
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`“overreaching” in a later-filed application as to the scope of what was
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`invented at the time of the earlier-filed application by requiring that the
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`invention be described in “such detail that . . . future claims can be
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`determined to be encompassed within the . . . original creation.” Vas-Cath
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`Inc. v. Mahurkar, 935 F.2d 1555, 1561 (Fed. Cir. 1991). Specifically, to
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`satisfy the written description requirement, the disclosure of the earlier-filed
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`application must “reasonably convey[]” to one of ordinary skill in the art
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`that, as of the filing date sought, “the inventor had possession” of the subject
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`matter now claimed. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
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`1351–52 (Fed. Cir. 2010); Vas-Cath, 935 F.2d at 1563–64. The test for
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`written description, therefore, requires “an objective inquiry into the four
`
`corners of the specification from the perspective of a person of ordinary skill
`
`in the art” to determine whether the specification “show[s] that the inventor
`
`[had] actually invented,” or possessed, each feature now included as a claim
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`limitation. Ariad Pharm., 598 F.3d at 1351; see New Railhead Mfg., 298
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`F.3d at 1295.
`
`The Federal Circuit has established specific requirements for written
`
`description of genus claims, i.e., claims encompassing two or more
`
`embodiments, that “use functional language to define the[ir] boundaries.”
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`Ariad Pharm., 598 F.3d at 1349–50; see Billups-Rothenberg, Inc. v.
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`Associated Reg’l & Univ. Pathologists, Inc., 642 F.3d 1031, 1037 (Fed. Cir.
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`2011). Claim 1 of the ’565 patent is a functionally-defined genus claim
`
`because it recites the function, or desired or useful result, of “inactivat[ion]”
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`of “at least one” Grx3 and Grx4 proteins, and further recites that this
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`inactivation “results from” any one of a number of different means:
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`“deletion of one or more nucleotides of an endogenous gene encoding” the
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`protein, “insertion of one or more nucleotides into an endogenous gene
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`encoding” the protein, or “combinations thereof.” Ex. 1001, 91:15–26; see
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`Tr. 8:6–7, 11:3–4; Billups-Rothenberg, 642 F.3d at 1037; Ariad Pharm., 598
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`F.3d at 1349–50. We, therefore, must determine whether the ’952 and
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`’209 provisionals meet the governing standards for written description
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`support of this genus claim.
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`Evaluating written description support for genus claims presents the
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`issue of whether the disclosure in the specification demonstrates that the
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`inventor had possession of species sufficient to support a claim to the totality
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`of the functionally-defined genus. Carnegie Mellon Univ. v. Hoffman-La
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`Roche Inc., 541 F.3d 1115, 1126 (Fed. Cir. 2008); Ariad Pharm., 598 F.3d at
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`1349–50. To meet the written description requirement for such claims, the
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`specification must disclose either: (1) “a representative number of species
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`falling within the scope of the genus,” “precise[ly] defin[ed], such as by
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`structure, formula, chemical name, physical properties, or other properties,”
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`or (2) “structural features common to the members of the genus.” Ariad
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`Pharm., 598 F.3d at 1350; Carnegie Mellon, 541 F.3d at 1122–26; Regents
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`of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566–69 (Fed. Cir.
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`1997). A functionally-defined genus claim also can “meet the written
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`description requirement if a reasonable structure-function correlation is
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`established, whether by the inventor as described in the specification or
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`known in the art at the time of the filing date.” AbbVie Deutschland GmbH
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`& Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1301 (Fed. Cir. 2014);
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`see Ariad Pharm., 598 F.3d at 1350. These standards are premised on the
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`basic principle that one of ordinary skill in the art “must be able to ‘visualize
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`or recognize the identity of the members of the genus’” upon reviewing the
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`disclosure. Carnegie Mellon, 541 F.3d at 1124 (quoting Eli Lilly, 119 F.3d
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`at 1569); see Ariad Pharm., 598 F.3d at 1350.
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`Here, the disclosures of the ’952 and ’209 provisionals cited by the
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`parties as relevant to claim 1 of the ’565 patent divide into two categories.
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`One category includes disclosures regarding inserting or deleting nucleotides
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`of genes—not specific to the GRX3 or GRX4 gene. Ex. 1010 ¶¶ 67–68, 213,
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`229, 258–264, 268; Ex. 1011 ¶¶ 73–74, 244, 260, 289–295, 299; see Pet.
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`20–23; PO Resp. 7–12; Reply 2–4. For example, the ’952 and ’209
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`provisionals define “engineer” to include “inserting a polynucleotide and/or
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`polypeptide heterologous to the microorganism and mutating a
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`polynucleotide and/or polypeptide native to the microorganism.” Ex. 1010
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`¶ 67; Ex. 1011 ¶ 73 (emphases added). The provisionals, in turn, define
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`“mutation,” to include, for example, “deletions, or insertions of single or
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`multiple residues in a polynucleotide,” or “an insertion, or a deletion of part
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`or all of a gene.” Ex. 1010 ¶ 68; Ex. 1011 ¶ 74 (emphases added). The
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`provisionals explain that “an engineered or modified microorganism can also
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`include alteration, disruption, deletion, or knocking-out of a gene or
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`polynucleotide.” Ex. 1010 ¶ 213; Ex. 1011 ¶ 244 (emphasis added). The
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`provisionals further refer to “known deletion techniques” and include a
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`section, titled “Genetic insertions and deletions,” which references known
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`techniques to “introduce” or “integrat[e]” genes or “nucleic acid
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`molecule[s]” into yeast and to “remove[]” such “introduced marker genes.”
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`Ex. 1010 ¶¶ 258–263, 268; Ex. 1011 ¶¶ 289–294, 299.
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`The other category includes disclosures specifically referring to
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`deleting, attenuating, or reducing either or both the GRX3 and GRX4 genes.
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`Ex. 1010 ¶¶ 28, 154–58, claim 56; Ex. 1011 ¶¶ 31, 178, 180–82, claim 56;
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`see Pet. 17–24; PO Resp. 7–12; Reply 2–4. For example, the
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`’952 provisional states that the disclosed recombinant microorganism “may
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`be engineered to delete and/or attenuate one or more genes selected from the
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`group consisting of GRX3 and GRX4, or homologs thereof.” Ex. 1010 ¶ 28.
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`The later-filed ’209 provisional adds that these genes may be reduced,
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`specifically disclosing that the microorganism “may be engineered to delete,
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`reduce, and/or attenuate” either or both the GRX3 and GRX4 genes.
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`Ex. 1011 ¶ 31.
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`Petitioner, with supporting testimony from Dr. Thiele, takes the
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`position that one of ordinary skill in the art would understand these
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`disclosures in the ’952 and ’209 provisionals regarding reduction and
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`attenuation of the GRX3 and GRX4 genes to accomplish “less than complete
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`inactivation” of the corresponding protein. Pet. 17–18; Ex. 1002 ¶ 29.
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`Patent Owner does not dispute this testimony or otherwise address the
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`meaning of reduction or attenuation to a person of ordinary skill in the art.
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`See PO Resp. 5–15; Reply 2. We credit Dr. Thiele’s testimony on this point
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`and, therefore, find that the Grx3 and Grx4 proteins in yeast engineered to
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`reduce or attenuate either or both GRX3 and GRX4 genes would not be
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`“inactivated” within the meaning of claim 1 of the ’565 patent. Ex. 1002
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`¶¶ 29–30; see supra Section II.B.1. Accordingly, the disclosed reduced or
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`attenuated GRX3 and GRX4 genes do not fall within the scope of claim 1 of
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`the ’565 patent, and do not provide written description support for the claim.
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`As to the disclosures in the ’952 and ’209 provisionals regarding
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`deletion of the GRX3 and GRX4 genes, Petitioner argues that one of ordinary
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`skill would understand the disclosures directed to deleting either or both the
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`GRX3 and GRX4 genes “to only encompass, at best, a complete deletion of
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`the GRX3 and/or GRX4 genes.” Pet. 18–19; Ex. 1002 ¶ 31. Patent Owner
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`contests Petitioner’s interpretation, citing to the disclosures in the
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`provisionals regarding “a deletion of part or all of a gene.” PO Resp. 9–10,
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`13–14 (emphasis omitted); see Ex. 1010 ¶ 68; Ex. 1011 ¶ 74. We agree with
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`Patent Owner. Petitioner’s proposed interpretation takes an overly narrow
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`view of the relevant disclosures that is unjustified in light of other statements
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`in each provisional. In each, the disclosures that microorganisms may be
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`“engineered to delete” either or both GRX3 and GRX4 genes (Ex. 1010
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`¶¶ 28, 158; Ex. 1011 ¶¶ 31, 182 (emphasis added)) ties to the definitions of
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`“engineer,” which “includes . . . mutati[ons]” (Ex. 1010 ¶ 67; Ex. 1011
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`¶ 73), and “mutation,” which includes “deletions, or insertions of single or
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`multiple residues in a polynucleotide,” or “an insertion, or a deletion of part
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`or all of a gene” (Ex. 1010 ¶ 68; Ex. 1011 ¶ 74). Therefore, based on the
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`express language of the provisionals, we find that one of ordinary skill in the
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`art would understand the references to deleting either or both the GRX3 and
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`GRX4 genes to refer to deleting “all or part” of these genes—more
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`specifically, both complete gene deletion (deletion of all nucleotides of the
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`gene) and partial gene deletion (deletion of only a subset of nucleotides of
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`the gene). Even so, however, the disclosures of the ’952 and ’209
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`provisionals fall short of the required standards for written description, for
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`the reasons we explain below.
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`First, the disclosures in the ’952 and ’209 provisionals do not disclose
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`a representative number of species falling within the scope of the claimed
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`genus and, thus, fail to show that the inventors had “conceived and described
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`sufficient representative species encompassing the breadth of the genus” of
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`insertions, deletions, and combinations of insertions and deletions in either
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`or both the GRX3 or GRX4 genes that inactivate the corresponding protein.
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`AbbVie, 759 F.3d at 1300. Starting with deletions, the ’952 and
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`’209 provisionals do reference both complete and partial deletion of the
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`GRX3 and GRX4 genes, as we noted above. Complete deletion of the GRX3
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`or GRX4 genes results in non-expression of the corresponding protein,
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`making the protein “inactive,” as recited in claim 1. See Ex. 1002 ¶¶ 31–32.
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`Based on the disclosures in the ’952 and ’209 provisionals regarding
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`“eliminat[ion]” of genes according to “known deletion techniques” and
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`specifically regarding “delet[ion]” of either or both GRX3 and GRX4 genes,
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`together with Petitioner’s acknowledgement that complete deletion of the
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`GRX3 and GRX4 genes was known in the art when the provisionals were
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`filed, we find that the provisionals sufficiently disclose species involving
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`complete deletion of the GRX3 gene, the GRX4 gene, and the GRX3 and
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`GRX4 genes, which fall within the scope of claim 1. See Ex. 1010 ¶¶ 28,
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`154–158, 268; Ex. 1011 ¶¶ 31, 178–182, 299; Ex. 1002 ¶¶ 31–32, 37, 40–
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`