Trials@uspto.gov
`571-272-7822
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`Paper 9
`Entered: March 4, 2014
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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.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`

`

`Case IPR2013-00539
`Patent 8,273,565 B2
`
`
`ButamaxTM Advanced Biofuels LLC (“Butamax”) filed a Petition to institute
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`an inter partes review of claims 1-19 of U.S. Patent No. 8,273,565 B2 (“the ’565
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`patent”) pursuant to 35 U.S.C. §§ 311-319. Paper 4 (“Pet.”). Patent Owner
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`Gevo, Inc. (“Gevo”) did not file a preliminary response to the Petition. We have
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`jurisdiction under 35 U.S.C. § 314. For the reasons that follow, the Board has
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`determined to institute an inter partes review of claims 1-9 and 11-19.
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`
`
`I. BACKGROUND
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`The standard for instituting an inter partes review is set forth in 35 U.S.C.
`
`§ 314(a):
`
`THRESHOLD – The Director may not authorize an inter partes
`review to be instituted unless the Director determines that the
`information presented in the petition filed under section 311 and any
`response filed under section 313 shows that there is a reasonable
`likelihood that the petitioner would prevail with respect to at least 1 of
`the claims challenged in the petition.
`
`In its Petition, Butamax challenges claims 1-19 of the ’565 patent as unpatentable,
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`asserting that claims 1-8 and 11-19 are anticipated under 35 U.S.C. § 102(e) and
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`claims 1-19 would have been obvious under 35 U.S.C. § 103(a). Pet. 11-58. Upon
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`consideration of the Petition, we conclude that there is a reasonable likelihood
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`Butamax will prevail in establishing that claims 1-4, 6-8, and 11-19 are anticipated,
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`and claims 1-9, 11, 13, 14, and 16-19 would have been obvious. Accordingly, we
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`grant the Petition to institute inter partes review as to claims 1-9 and 11-19, but
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`deny the Petition as to claim 10.
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`A. District Court Proceedings Involving the ’565 Patent
`
`Butamax informs us that the ’565 patent was previously the subject of two
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`actions between Butamax and Gevo before the U.S. District Court for the District
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`of Delaware. Id. at 3-4. According to the Petition, both actions were filed on
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`
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`2
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`Case IPR2013-00539
`Patent 8,273,565 B2
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`September 25, 2011, which, if correct, would bar inter partes review under 35
`
`U.S.C. § 315(b). See Pet. 3; Part II.A below. Based on our independent review of
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`the filings, however, the cases were filed on September 25, 2012. See Ex. 3001
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`(Compl. for Declaratory J. of Non-Infringement, and Invalidity, ButamaxTM
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`Advanced Biofuels LLC v. Gevo, Inc., No. 12-1201 (SLR) (D. Del. Sept. 25,
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`2012)); Ex. 3002 (Compl., Gevo, Inc. v. ButamaxTM Advanced Biofuels LLC, No.
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`12-1202 (SLR) (D. Del. Sept. 25, 2012)).
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`Specifically, on September 25, 2012, Butamax filed suit against Gevo for
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`declaratory judgment of invalidity of the claims of the ’565 patent, ButamaxTM
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`Advanced Biofuels LLC v. Gevo, Inc., No. 12-1201 (SLR) (“First District Court
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`Action”). Ex. 3001. On November 5, 2012, Gevo filed an answer asserting
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`counterclaims of infringement of one or more claims of the ’565 patent.1 Ex. 3003
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`(Answer to Compl. for Declaratory J. of Non-Infringement and Invalidity, and
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`Countercl., ButamaxTM Advanced Biofuels LLC v. Gevo, Inc., No. 12-1201 (SLR)
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`(D. Del. Nov. 5, 2012)).
`
`On September 25, 2012, the same day Butamax filed the First District Court
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`Action, Gevo filed suit against Butamax alleging infringement of one or more
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`claims of the ’565 patent, Gevo, Inc. v. ButamaxTM Advanced Biofuels LLC, No.
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`12-1202 (SLR) (“Second District Court Action”). Ex. 3002.
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`On August 9, 2013, pursuant to a joint stipulation filed by the parties, the
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`court dismissed, without prejudice, Butamax’s claims and counterclaims against
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`Gevo and dismissed, with prejudice, Gevo’s claims and counterclaims against
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`Butamax in the First and Second District Court Actions. See Pet. 3.
`
`
`1 We note that Butamax’s Petition does not include relevant details of the First
`District Court Action, specifically, that the answer featured counterclaims alleging
`infringement of the ’565 patent.
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`
`
`
`3
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`

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`Case IPR2013-00539
`Patent 8,273,565 B2
`
`
`B. The ’565 Patent (Ex. 1001)
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`The ’565 patent, titled “Methods of Increasing Dihydroxy Acid Dehydratase
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`Activity to Improve Production of Fuels, Chemicals, and Amino Acids,” is
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`directed to recombinant yeast microorganisms with increased activity of dihydroxy
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`acid dehydratase (“DHAD”). Ex. 1001, Abstract, col. 1, l. 29–col. 2, l. 25. DHAD
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`is an enzyme that catalyzes steps in various biosynthetic pathways that produce
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`metabolites, such as isobutanol, a common fuel additive. Id. at Abstract, col. 1, ll.
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`46-66, Fig. 1. Increased DHAD activity is favorable for production of these
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`metabolites. Id. at col. 1, l. 65–col. 2, l. 20, col. 24, ll. 31-33. In addition, the
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`patent is directed to methods of producing such metabolites by cultivating the
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`recombinant microorganisms in a culture medium containing a feedstock providing
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`a carbon source. Id. at Abstract, col. 8, ll. 55-63.
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`The specification of the ’565 patent discloses various embodiments,
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`including recombinant microorganisms with increased DHAD activity resulting
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`from alterations in the regulation, expression, and activity of proteins monothiol
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`glutaredoxin-3 (“GRX3”), monothiol glutaredoxin-4 (“GRX4”), or both GRX3 and
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`GRX4. Id. at col. 24, ll. 36-45; see id. at col. 24, ll. 1-30. The specification also
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`discloses recombinant microorganisms with improved DHAD activity resulting
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`from overexpression of one or more nucleotides encoding activator of ferrous
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`transport (“Aft”) proteins, Aft1 and Aft2, or constitutively active Aft proteins. Id.
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`at col. 2, ll. 9-25, col. 4, ll. 14-26, col. 15, ll. 49-54. The DHAD in these
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`embodiments may be localized in either the cytosol or the mitochondria of the
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`microorganisms. Id. at col. 3, ll. 30-46, col. 16, ll. 33-34, col. 24, ll. 36-45.
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`Further, the recombinant microorganisms may be one of various disclosed yeast
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`genera and species, including Saccharomyces cerevisiae. See id. at col. 7, l. 49–
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`col. 8, l. 54.
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`4
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`Case IPR2013-00539
`Patent 8,273,565 B2
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`
`C. Illustrative Claim
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`Claim 1, the only independent claim of the ’565 patent, is illustrative of the
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`challenged claims:
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`1. A recombinant yeast microorganism comprising a recombinantly
`overexpressed polynucleotide encoding a dihydroxy acid
`dehydratase (DHAD),
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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 col. 91, ll. 15-26 (line breaks added).
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`Butamax relies on the following prior art:
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`D. The Prior Art
`
`Anthony US 2010/0081179 A1
`Li
`US 2009/0163376 A1
`Flint
`WO 2011/103300 A2
`
`Apr. 1, 2010
`June 25, 2009
`Aug. 25, 2011
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`
`
`
`
`Ex. 1005
`Ex. 1015
`Ex. 1003
`
`
`Karin M. Overkamp et al., Metabolic Engineering of Glycerol Production in
`Saccharomyces cerevisiae, 68 APPLIED & ENVTL. MICROBIOLOGY 2814 (2002).
`(Ex. 1009.)
`
`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.)
`
`Sergi Puig et al., Coordinated Remodeling of Cellular Metabolism During Iron
`Deficiency Through Targeted mRNA Degradation, 120 CELL 99 (2005). (Ex.
`1006.)
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`
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`5
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`Case IPR2013-00539
`Patent 8,273,565 B2
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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.)
`
`
`E. The Asserted Grounds
`
`Butamax challenges the claims of the ’565 patent on the following grounds:
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`Challenged Claims Basis
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`Reference[s]
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`1-8 and 11-19
`1-4, 6-8, and 11-19
`5
`9
`10
`
`
`§ 102(e) Flint
`§ 103(a) Anthony, Puig, and Ojeda
`§ 103(a) Anthony, Puig, Ojeda, and Li
`§ 103(a) Anthony, Puig, Ojeda, and van Maris
`§ 103(a) Anthony, Puig, Ojeda, and Overkamp
`
`II. ANALYSIS
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`A. Statutory Bar Under 35 U.S.C. § 315
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`We first address whether the two previous district court actions between
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`Butamax and Gevo concerning the ’565 patent bar inter partes review pursuant to
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`35 U.S.C. § 315. We determine that neither action presents a statutory bar.
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`First, we agree with Butamax that its challenge to the validity of claims of
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`the ’565 patent in the First District Court Action does not prohibit institution of
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`inter partes review under 35 U.S.C. § 315(a)(1), because Butamax voluntarily
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`dismissed its invalidity claim without prejudice. Pet. 3-4. Section 315(a)(1)
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`provides:
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`An inter partes review may not be instituted if, before the date on
`which the petition for such a review is filed, the petitioner or real
`party in interest filed a civil action challenging the validity of a claim
`of the patent.
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`35 U.S.C. § 315(a)(1). We have held that actions dismissed without prejudice
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`“do[] not trigger th[is] statutory bar.” Cyanotech Corp. v. Bd. of Trs. of the Univ.
`
`of Ill., IPR2013-00401, slip op. at 11-12 (PTAB Dec. 19, 2013) (Paper 17); see
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`6
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`Patent 8,273,565 B2
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`Invue Sec. Prods., Inc. v. Merchandising Techs., Inc., IPR2013-00122, slip op. at
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`8-10 (PTAB June 27, 2013) (Paper 17). Our interpretation of § 315(a) is guided by
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`precedent from the Federal Circuit and the reasoning of other federal courts
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`treating an action dismissed without prejudice as a nullity that leaves the parties as
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`if the action never had been brought. Cyanotech, slip op. at 9-10; Invue, slip op. at
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`9-10; see Bonneville Assocs., Ltd. P’ship v. Barram, 165 F.3d 1360, 1364 (Fed.
`
`Cir. 1999) (“The rule in the federal courts is that [t]he effect of a voluntary
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`dismissal without prejudice pursuant to Rule 41(a) is to render the proceedings a
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`nullity and leave the parties as if the action had never been brought.”) (internal
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`quotations omitted). It is also consistent with legislative intent that inter partes
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`review be an alternative to civil litigation. Cyanotech, slip op. at 11 (reasoning that
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`an alternative interpretation of § 315(a) would “frustrate the Congressional intent
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`of creating an adjudicative process as an alternative to civil litigation, and would
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`lead to the unjustified scenario where a party could challenge a patent in civil
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`litigation but not in inter partes review”). Accordingly, Butamax’s complaint in
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`the First District Court Action does not invoke the statutory bar of § 315(a).
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`Second, we determine that Gevo’s prior allegations of infringement of
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`claims of the ’565 patent against Butamax in the First and Second District Court
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`Actions are not a statutory bar to institution of inter partes review pursuant to 35
`
`U.S.C. § 315(b). Section 315(b) states:
`
`An inter partes review may not be instituted if the petition requesting
`the proceeding is filed more than 1 year after the date on which the
`petitioner, real party in interest, or privy of the petitioner is served
`with a complaint alleging infringement of the patent.
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`35 U.S.C. § 315(b). Here, on September 28, 2012, Gevo served Butamax with its
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`first complaint alleging infringement of the ’565 patent, which triggered the one-
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`year period of § 315(b)—even though Gevo’s claims later were dismissed with
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`
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`7
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`Patent 8,273,565 B2
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`prejudice. See St. Jude Med., Cardiology Div., Inc. v. Volcano Corp., IPR2013-
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`00258, 2013 WL 5947710, at *5 (PTAB Oct. 16, 2013) (“Service of a complaint
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`alleging infringement triggers applicability of § 315(b), even if that complaint is
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`later dismissed with prejudice.”); Ex. 3004 (Summons in a Civil Action, Gevo, Inc.
`
`v. ButamaxTM Advanced Biofuels LLC, No. 12-1202 (SLR) (D. Del. Sept. 28,
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`2012)). Yet because Butamax filed its Petition less than one year later, on August
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`30, 2013, the Petition was filed timely under § 315(b). See Paper 5.
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`B. Claim Interpretation
`
`Consistent with the statute and legislative history of the Leahy-Smith
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`America Invents Act, Pub. L. No. 112-29 (2011), the Board interprets claims using
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`the “broadest reasonable construction in light of the specification of the patent in
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`which [they] appear[].” 37 C.F.R. § 42.100(b); see also Office Patent Trial
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`Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14, 2012). We afford a
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`presumption that a claim term carries its “ordinary and customary meaning,” which
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`is “the meaning that the term would have to a person of ordinary skill in the art in
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`question” at the time of the invention. In re Translogic Tech., Inc., 504 F.3d 1249,
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`1257 (Fed. Cir. 2007). This presumption, however, is rebutted when the patentee
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`acts as his own lexicographer, giving the term a particular meaning in the
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`specification with “reasonable clarity, deliberateness, and precision.” In re
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`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). We interpret the following claim
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`terms of the challenged claims as part of our analysis.
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`1. “Inactivated”
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`Butamax asserts that “inactivated,” as used in the following phrase of
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`claim 1, “said recombinant yeast microorganism is engineered to comprise at least
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`one inactivated monothiol glutaredoxin,” Ex. 1001, col. 91, ll. 17-19 (emphasis
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`added), “should be construed to mean that the GRX3 and/or GRX4 protein lacks
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`
`
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`8
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`

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`Case IPR2013-00539
`Patent 8,273,565 B2
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`all activity and excludes GRX3 and/or GRX4 proteins having reduced, attenuated
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`or partial activities.” Pet. 7. Butamax supports its argument with statements in an
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`Examiner-Initiated Interview Summary in the prosecution history of the ’565
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`patent in which Gevo “noted that the meaning of ‘inactivate’ is to render inactive
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`so that GRX3 and GRX4 proteins have no activity thereof,” and the Patent
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`Examiner “agree[d].” Id. at 7; Ex. 1012, Examiner-Initiated Interview Summary
`
`(May 17, 2012). Butamax contends Gevo has foregone its opportunity to
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`challenge and, thus, has acquiesced to the Examiner’s claim construction. Pet. 7-8
`
`& n.1.
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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 Ex. 3005
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`(THE AMERICAN HERITAGE MEDICAL DICTIONARY 402 (Rev. ed. 2007)) (defining
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`“inactivate” as “[t]o render nonfunctional”); Ex. 3006 (STEDMAN’S MEDICAL
`
`DICTIONARY 959 (28th ed., Lippincott Williams & Wilkins 2006)) (defining
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`“inactivate” as “[t]o destroy the biologic activity or the effects of an agent or
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`substance”); Ex. 3007 (MERRIAM-WEBSTER’S COLLEGIATE DICTIONARY 584 (10th
`
`ed. 2000)) (defining “inactivate” as “to make inactive,” and “inactive” as
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`“chemically” or “biologically inert”); Ex. 3008 (DICTIONARY OF SCIENCE AND
`
`TECHNOLOGY 1092 (Christopher Morris, ed. 1992)) (defining “inactivate” as “to
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`render inactive; destroy the activity of”). This customary meaning, thus, requires a
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`lack of all activity or functionality.
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`The usage of “inactivated” and related terms in the specification of the ’565
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`patent neither elucidates the meaning of the term nor indicates any deviation from
`
`its ordinary and customary meaning. Dependent claims 9 and 10 recite the term
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`“inactivate” in a manner similar to “inactivated” in claim 1: “said recombinant
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`yeast microorganism is further engineered to inactivate one or more endogenous
`
`
`
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`9
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`Case IPR2013-00539
`Patent 8,273,565 B2
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`pyruvate decarboxylase (PDC)” (claim 9) and “glycerol-3-phosphate
`
`dehydrogenase (GPD)” (claim 10). Ex. 1001, col. 91, ll. 58-65 (emphasis added).
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`These claims, therefore, offer no further clarity regarding the meaning of the term.
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`References to the term in other portions of the specification likewise do not define
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`or otherwise explicate its meaning. Upon review of the record, we are not
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`persuaded that the inventors of the ’565 patent acted as their own lexicographer to
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`alter the ordinary and customary meaning of the term “inactivated.”
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`Accordingly, to the extent Butamax’s proposed construction of “inactivated”
`
`requires a “lack[ of] all activity,” Pet. 7, we conclude that it is consistent with the
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`plain and ordinary meaning of the term as well as usage of the term in the
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`specification of the ’565 patent. We, however, reject the remainder of Butamax’s
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`proffered construction, “exclud[ing] GRX3 and/or GRX4 proteins having reduced,
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`attenuated or partial activities,” id., because it is directed to the scope of claim 1,
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`rather than the meaning of the term “inactivated.” Pet. 7. We, therefore, construe
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`“inactivated” to mean lacking all activity or functionality.
`
`2. “[W]herein 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”
`
`Butamax further requests a construction of the last limitation of claim 1:
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`“[W]herein said inactivated monothiol glutaredoxin results from the deletion of one
`
`or more nucleotides of an endogenous gene encoding said monothiol glutaredoxin,
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`the insertion of one or more nucleotides into an endogenous gene encoding said
`
`monothiol glutaredoxin, or combinations thereof.” Pet. 8-10. Butamax asserts
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`there is no limitation on the nucleotides that can be inserted or deleted to produce
`
`an inactivated GRX3 or GRX4 protein, with one exception resulting from an
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`amendment in the prosecution history of the ’565 patent. Id. at 8-9. Specifically,
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`10
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`Butamax argues the inserted or deleted nucleotides cannot occur in the regulatory
`
`regions associated with the endogenous genes, because Gevo deleted the phrase
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`“or regulatory region thereof” from claim 1 in response to a rejection by the
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`Examiner. See id. at 9; Ex. 1012, Amendment Under 37 CFR § 1.116, at 2, 6 (May
`
`8, 2012). Butamax, therefore, proposes that the claim limitation encompasses:
`
`any deletion of one or more nucleotides, any insertion of one or more
`nucleotides, or any combination of any deletion and any insertion of
`one or more nucleotides in an endogenous yeast GRX3 and/or GRX4
`gene that results in any “inactivated” GRX3 and/or GRX4 protein, . . .
`so long as the deletions [or] insertions . . . do not occur in the
`regulatory regions associated with the endogenous genes.
`
`Pet. 9-10.
`
`Butamax’s asserted grounds of unpatentability in its Petition, however, are
`
`unaffected by whether the recited inserted or deleted nucleotides can occur in
`
`regulatory regions associated with the genes. See id. at 11-59. We, therefore,
`
`conclude that whether the inserted or deleted nucleotides recited in claim 1 can
`
`occur in regulatory regions is not determinative of whether Butamax will establish
`
`that the prior art anticipates or renders obvious the claims of the ’565 patent.
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`Accordingly, we need not construe the limitation at this stage of the proceeding.
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`3. Yeast Genera and Species
`
`Butamax argues claims 1-16 and 19, which do not specify the genus or
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`species of the recited yeast microorganism, must encompass at least the genera and
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`species recited in claims 17 and 18. See id. at 10. “Under the doctrine of claim
`
`differentiation, dependent claims are presumed to be of narrower scope than the
`
`independent claims from which they depend” and, thus, independent claims are
`
`presumed to be “at least as broad as the claims that depend from them.” AK Steel
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`Corp. v. Sollac, 344 F.3d 1234, 1242 (Fed. Cir. 2003) (holding that because
`
`dependent claims recited aluminum with “‘up to about 10% silicon,’” the
`
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`11
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`independent claims from which the claims depend “must also encompass
`
`aluminum with up to about 10% silicon”); see Alcon Research, Ltd. v. Apotex Inc.,
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`687 F.3d 1362, 1367 (Fed. Cir. 2012) (holding that where a dependent claim
`
`recited a specific range of concentrations, the independent claim “must cover at
`
`least that range”). This presumption applies and has not been rebutted. Therefore,
`
`we agree with Butamax that independent claim 1 must encompass at least the yeast
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`genera and species recited in dependent claims 17 and 18. Further, because claims
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`2-16 and 19, which depend from claim 1, do not limit the genera or species of
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`yeast, these claims also cover at least the yeast genera and species recited in claims
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`17 and 18.
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`4. Localization of DHAD
`
`
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`Similar to its argument regarding yeast genera and species above, Butamax
`
`contends that independent claim 1 must encompass yeast with DHAD localized in
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`either the cytosol or the mitochondria. Pet. 10-11. For support, Butamax notes
`
`that claim 1 does not limit where DHAD is localized, but dependent claims 11 and
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`12 specify that the recited DHAD is “localized” in the “cytosol” and the
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`“mitochondria,” respectively. Id.; Ex. 1001, col. 92, ll. 14-18. Again, we agree
`
`that the presumption that independent claims are at least as broad as their
`
`dependent claims applies and has not been rebutted. We, thus, conclude that
`
`claim 1 covers at least DHAD localized in the cytosol and the mitochondria. We
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`likewise determine that claims 2-10 and 13-19, which depend from claim 1 and do
`
`not specify where the recited DHAD is localized, encompass at least DHAD
`
`localized in the cytosol and the mitochondria.
`
`C. Asserted Grounds of Unpatentability
`
`We turn now to Butamax’s asserted grounds of unpatentability to determine
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`whether Butamax has met the threshold standard of 35 U.S.C. § 314(a).
`
`
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`12
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`Case IPR2013-00539
`Patent 8,273,565 B2
`
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`1. Anticipation of Claims 1-8 and 11-19 by Flint (Ex. 1003)
`
`Butamax first asserts that claims 1-8 and 11-19 of the ’565 patent are
`
`unpatentable under 35 U.S.C. § 102(e) as anticipated by Flint. Pet. 12-29. Flint,
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`PCT Application No. WO 2011/103300 A2, was filed on February 17, 2011 and
`
`claims priority to U.S. Provisional Application No. 61/305,333 (“Flint ’333
`
`provisional”), filed on February 17, 2010. Ex. 1003, [10], [22], [30], [43]. Flint’s
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`earliest claimed priority date is, therefore, February 17, 2010.
`
`The ’565 patent, however, was filed on September 27, 2011 as a divisional
`
`of 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, [62], col. 1, ll. 9-12. The ’565
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`patent further claims priority to two provisional applications: U.S. Provisional
`
`Application Serial Nos. (1) 61/350,209 (“’209 provisional”), filed June 1, 2010,
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`and (2) 61/263,952 (“’952 provisional”), filed November 24, 2009. Id. at [60],
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`col. 1, ll. 12-17. The earliest claimed priority date of the ’565 patent is, therefore,
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`November 24, 2009—before that of Flint.
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`Accordingly, as a threshold to its argument that Flint anticipates the ’565
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`patent, Butamax contends the ’565 patent is not entitled to priority to the ’952 and
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`’209 provisionals. If this argument succeeds, the ’565 patent would have an
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`effective filing date of no earlier than November 24, 2010 and Flint—with priority
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`to the filing date of the Flint ’333 provisional, February 17, 2010—would be prior
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`art under § 102(e). We address Butamax’s arguments regarding the effective filing
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`date of the ’565 patent before turning to its assertions regarding Flint’s anticipatory
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`disclosure.
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`a. Effective Filing Date of the ’565 Patent
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`Butamax makes several arguments that the ’952 and ’209 provisionals do
`
`not provide written description support for the ’565 patent claims, and thus, the
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`claims are not entitled to priority to either application. See Pet. 12-25; Chiron
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`Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 (Fed. Cir. 2004) (“[T]he ’56[5]
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`patent may only claim priority to an earlier application if the earlier application
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`fulfills the requirements of § 112, first paragraph[, which] requires, in part, that the
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`application ‘shall contain a written description of the invention . . . .’”).
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`For example, Butamax argues that the ’952 and ’209 provisionals do not
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`describe the full scope of either the inactivated GRX3 or GRX4 proteins, or the
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`deleted nucleotides, inserted nucleotides, or combination of deleted and inserted
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`nucleotides of genes resulting in inactivated GRX3 or GRX4 proteins recited in
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`claim 1 of the ’565 patent. Pet. 12-23. Butamax identifies two categories of
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`relevant disclosures in the provisionals—which, according to Butamax, are
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`insufficient to convey the full scope of the invention recited in claim 1.
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`First, Butamax addresses references in the ’952 and ’209 provisionals to
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`“delet[ing],” “attenuat[ing],” or “reduc[ing]” GRX3 or GRX4 genes. Ex. 1010
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`¶¶ 0028, 0154-0158; Ex. 1011 ¶¶ 0031, 00178-00182; see Pet.16-19; Ex. 1002
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`¶¶ 29-33. With respect to the disclosures regarding reducing or attenuating GRX3
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`or GRX4 genes, Butamax cites to the declaration of Dr. Dennis J. Thiele, Ph.D.,
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`who declares a person of ordinary skill in the art would understand reduction and
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`attenuation of GRX3 or GRX4 genes to accomplish less than complete inactivation
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`of the corresponding proteins. Ex. 1002 ¶ 29. Therefore, the GRX3 and GRX4
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`proteins would not be “inactivated” as recited in claim 1. Id. ¶¶ 29-30; see supra
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`Part II.B.1. As to the disclosures regarding deletion of GRX3 or GRX4 genes,
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`Dr. Thiele declares that one of ordinary skill would understand deletion of GRX3
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`or GRX4 genes to encompass only complete deletion of the gene, resulting in non-
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`expression of the corresponding protein. Ex. 1002 ¶ 31. Thus, at best, these
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`disclosures provide written description support for inactivated GRX3 or GRX4
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`proteins resulting from complete deletion of the corresponding gene. The ’952 and
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`’209 provisionals do not describe inactivated GRX3 or GRX4 proteins resulting
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`from partial deletion of the corresponding gene, i.e., deletion of one or more, but
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`less than all, nucleotides. Id. ¶¶ 32, 37. Nor do they describe inactivated GRX3 or
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`GRX4 proteins resulting from inserted nucleotides, or a combination of inserted
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`and deleted nucleotides.
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`Second, Butamax addresses disclosures regarding inserted or deleted
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`nucleotides of genes, not specific to the GRX3 or GRX4 gene. See id. ¶¶ 39-44;
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`Pet. 20-23. Specifically, both the ’952 and ’209 provisionals define “engineer” as
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`“any manipulation of a microorganism that results in a detectable change in the
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`microorganism,” including “but . . . not limited to inserting a polynucleotide
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`and/or polypeptide heterologous to the microorganism and mutating a
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`polynucleotide and/or polypeptide native to the microorganism.” Ex. 1010 ¶ 0067
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`(emphases added); Ex. 1011 ¶ 0073 (emphases added). “Mutation,” in turn, is
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`defined to “indicate[] any modification of a nucleic acid and/or polypeptide which
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`results in an altered nucleic acid or polypeptide,” including, “for example, point
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`mutations, deletions, or insertions of single or multiple residues in a
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`polynucleotide.” Ex. 1010 ¶ 0068 (emphasis added); Ex. 1011 ¶ 0074 (emphasis
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`added). Dr. Thiele declares that one of ordinary skill would not understand these
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`disclosures to provide any description of the type, location, or size of a deletion,
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`insertion, or combination of deletion and insertion of nucleotides that would result
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`in an inactivated GRX3 or GRX4 protein as recited in claim 1. Ex. 1002 ¶¶ 39-44.
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`On this uncontested record, Butamax has made a sufficient showing that the
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`’952 and ’209 provisionals would not convey, with reasonable clarity, to one of
`
`ordinary skill that the inventors had invented or were in possession of yeast with
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`inactivated GRX3 or GRX4 proteins resulting from insertions, deletions, or
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`combinations of insertions and deletions of nucleotides of the corresponding
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`gene—with the exception of complete gene deletion. See Centocor Ortho Biotech,
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`Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed. Cir. 2011) (“To satisfy the written
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`description requirement, the [specification] must convey with reasonable clarity to
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`those skilled in the art that, as of the filing date sought, [the inventor] was in
`
`possession of the invention, and . . . show that the inventor actually invented the
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`invention claimed.”) (internal quotations omitted). Thus, we are persuaded that the
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`provisionals do not provide written description support for claim 1 and its
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`dependent claims 2-19 and that the claims are not entitled to priority to these
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`applications, making the effective filing date of the ’565 patent no earlier than
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`November 24, 2010.2
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`b. Comparison of Flint’s Teachings to Claims 1-8 and 11-19
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`We now turn to Butamax’s arguments regarding the allegedly anticipatory
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`disclosure of Flint. Flint and the Flint ’333 provisional disclose “increased specific
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`activity of [DHAD]” in recombinant yeast cells of various genera and species,
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`including Saccharomyces cerevisiae. Ex. 1003, Abstract, ¶¶ 0003, 0009, 0012,
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`0025, 0103-0116, 0129, 0229-0233; Ex. 1004 ¶¶ 0001, 0008, 0011, 0024, 0098-
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`0111, 0144-0148. The applications teach that the specific activity of DHAD in
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`these recombinant yeast cells is increased by “delet[ing], mutat[ing], express[ing],
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`up-regulat[ing], or down-regulat[ing]” Fe-S cluster genes, including the GRX3 and
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`GRX4 genes. Ex. 1003 ¶ 0123, Table 8; Ex. 1004 ¶ 0163, Table 8; see Ex. 1003
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`¶¶ 240-242; Ex. 1004 ¶¶ 154-155. Such increased DHAD activity enhances
`
`
`2 Butamax makes alternative arguments regarding a lack of written description
`support in the ’952 and ’209 provisionals for the ’565 patent claims, but these
`arguments do not apply to all claims. See Pet. 24-25. Having found Butamax’s
`arguments applicable to all claims persuasive at this stage of the proceeding, we
`need not address Butamax’s other arguments.
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`production of products from biosynthetic pathways that include DHAD, such as
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`isobutanol. Ex. 1003 ¶¶ 0005-0006, 0138-0145; Ex. 1004 ¶¶ 0003-0004, 0111-
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`0116. Both applications further teach methods of making isobutanol by providing
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`a recombinant host cell and putting the cell in contact with a fermentable carbon
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`source substrate. Ex. 1003 ¶ 0016; Ex. 1004 ¶ 0015.
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`In support of its assertion that Flint anticipates claims 1-8 and 11-19,
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`Butamax sets forth teachings of Flint and the Flint ’333 provisional that it contends
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`meet each claim limitation and a detailed claim chart in the declaration of
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`Dr. Thiele. See Pet. 26-29; Ex. 1002, 26-40. For example, for claim 1, Flint and
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`the Flint ’333 provisional teach overexpressed DHAD in recombinant yeast cells—
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`which Butamax contends meets “[a] recombinant yeast microorganism comprising
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`a recombinantly overexpressed polynucleotide encoding . . . DHAD” as recited in
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`claim 1. Ex. 1002, 27-30; Ex. 1003 ¶¶ 0103-0116, 0229-0233; Ex. 1004 ¶¶ 0098-
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`0111, 0144-0148. Further, with respect to the inactivated GRX3 or GRX4 protein
`
`resulting from inserted or deleted nucleotides of the corresponding endogenous
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`gene, Butamax points to disclosures in Flint and the Flint ’333 provisional that
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`“delet[ing]” Fe-S cluster genes—including the GRX3 and GRX4 genes—increases
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`the specific activity of DHAD in such recombinant yeast cells. Ex. 1002, 27-30;
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`Ex. 1003 ¶ 0123, Table 8; Ex. 1004 ¶ 0163, Table 8. Butamax also notes that the
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`applications specifically detail th