UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`
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`BUTAMAXTM ADVANCED BIOFUELS LLC
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`Petitioner
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`V.
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`GEVO, INC.
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`Patent Owner
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`
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`CASE IPR: Unassigned
`
`
`PETITION FOR INTER PARTES REVIEW OF US. PATENT NO.
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`8,273,565 B2 UNDER 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-
`.123
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`Mail Stop "PA TENTBGARD"
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`Patent Trial and Appeal Board
`US. Patent and Trademark Office
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`PO. Box 1450
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`Alexandria, VA 22313-1450
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`

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`TABLE OF CONTENTS
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`II.
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`III.
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`IV.
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`VI.
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`INTRODUCTION .......................................................................................... 1
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`OVERVIEW ................................................................................................... 1
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`MANDATORY NOTICES ............................................................................ 2
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`GROUNDS FOR STANDING (37 CPR. § 42.104(a)) ................................ 5
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`PROCEDURAL STATEMENTS ................................................................... 5
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 CPR. § 42.104(b)) ......................................... 5
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`A. The '565 patent ........................................................................................ 5
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`B. Person of ordinary skill in the art ............................................................ 6
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`C. Claim construction .................................................................................. 6
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`l. "Inactivated" ....................................................................................... 7
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`2. "Engineered" recombinant yeast microorganisms comprising
`inactivated GRX3 and/or GRX4 protein that "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' ............................................. 8
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`3. Yeast genera/species ........................................................................ 10
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`4. DHAD localization .......................................................................... 10
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`Identification of Challenge (37 C.F.R. § 42.104(b)) ............................ ll
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`1. Ground 1: claims 1-8 and 11-19 are anticipated by Flint ................ 12
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`(a) None of claims 1-19 is entitled to the benefit of the filing
`dates of the '952 or '209 provisional applications .................... 12
`
`(i) The provisional applications do not describe the full
`scope of inactivated GRX3 and/or GRX4 of claims 1—
`19 ofthe '565 patent ......................................................... 13
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`(ii) The provisional applications do not describe the full
`genus of nucleotide deletions, insertions, or
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`ii
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`

`

`combinations of deletions and insertions into
`
`endogenous GRX3 and/or GRX4 genes .......................... 19
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`(iii) The provisional applications do not describe the broad
`scope of yeast genera or species of claims 1—16 and
`18-19 of the '565 patent, as acknowledged by the PTO... 24
`
`(iv) The provisional applications do not describe
`expressing mitochondrial1y-localized DHAD, as
`acknowledged by the PTO ............................................... 25
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`(b) Flint anticipates claims 1-8 and 11-19 ..................................... 2e
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`2. Ground 2: claims 1-4, 6-8 and 11—19 would have been obvious over
`
`Anthony in View of Puig and Ojeda ................................................ 29
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`(a) The knowledge of a POSA prior to the '565 patent ................. 30
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`(b) Claims 1—4, 6-8 and 11-19 would have been obvious over
`Anthony in View of Puig and Oj eda......................................... 34
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`(c) The art does not teach away from modifying a yeast
`containing recombinantly overexpressed DHAD .................... 43
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`3. Ground 3: claim 5 would have been obvious over Anthony in View
`of Puig and Ojeda, and further in view of the '3 76 publication ....... 47
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`4. Ground 4: claim 9 would have been obvious over Anthony in view
`of Puig and Ojeda, and further in view of van Maris ...................... 49
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`5. Ground 5: claim 10 would have been obvious over Anthony in View
`of Puig and Oj eda, and further in view of Overkamp ..................... 51
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`6. Gevo's alleged unexpected results do not rebut the primafacz'e
`obviousness ...................................................................................... 53
`
`(a)
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`Increased activity of recombinant overexpressed DHAD in
`yeast lacking GRX would have been expected........................ 54
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`(b) Gevo's proffered evidence of unexpected results is not
`reasonably commensurate with the scope of the claims .......... 56
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`VII. THERE IS A REASONABLE LIKELIHOOD THAT PETITIONER WILL
`
`PREVAIL WITH RESPECT TO AT LEAST ONE OF THE
`
`CHALLENGED CLAIMS ........................................................................... 59
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`VIII. CONCLUSION ............................................................................................. 59
`
`iii
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`1
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`I.
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`INTRGDUCTION
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`BUTAMAXTM ADVANCED BIOFUELS LLC's ("Petitioner") Petition for Inter
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`Partes Review ("Petition") seeks cancellation of claims 1-19 of US. Patent No.
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`8,273,565 ("the '565 patent") (BMXlOOl).
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`31' OVERvenw
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`Inter partes Review ("IPR") was established to improve patent quality and,
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`if warranted, cancel unpatentable claims. IPR is warranted, presently, because the
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`challenged claims should never have issued in View of the prior art. The limited
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`disclosure in its provisional applications does not support the '565 patent's claim
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`for priority benefit, and claims 1—8 and 11-19 are anticipated by intervening prior
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`art. In addition, the combinations of art identified herein — none of which were
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`before the original Examiner — show that a person of ordinary skill in the art
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`("POSA") had a reason, and the know-how, to arrive at the recombinant yeast and
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`method, claimed in the '565 patent, with a reasonable expectation of success,
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`regardless of the priority date to which the claims are entitled.
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`During original prosecution, patent owner Gevo, Inc., ("Gevo") overcame
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`prior art rejections by arguing that (i) the art taught away from the claimed yeast,
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`and (ii) the claimed yeast had some alleged unexpected property. But, as shown
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`herein, Gevo's arguments in both respects were directed, not to a recombinant
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`yeast as claimed, but instead to a native yeast. As explained in detail below and
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`supported by the accompanying declaration of Dr. Dennis J. Thiele, ("Thiele
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`Dec." BMX1002), the art would not have dissuaded a POSA from arriving at the
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`claimed recombinant yeast. Moreover, a POSA would have expected such a
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`recombinant yeast to act in line with Gevo's alleged unexpected property. Thus,
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`Gevo's arguments in favor of patentability made during original prosecution
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`should be accorded no weight.
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`In sum, a further review of the '565 patent claims is necessary because (i)
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`the art presented in the Petition demonstrates that the claims of the '565 patent
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`were either taught in the art or would have been obvious in view of the art
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`combinations presented herein; and (ii) Gevo's alleged teaching away and
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`unexpected property asserted do not relate to the claimed recombinant yeast, but
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`instead relate only to native yeast. There is a reasonable likelihood that Petitioner
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`will prevail with respect to at least one of the challenged claims in View of the
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`prior art discussed herein. IPR of the '565 patent is warranted.
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`IH. MANDATGDRY NOTICES
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`Real party-in—interest (37 GER. § 42.8(b)(1)): BUTAMAxTM ADVANCED
`
`BIOFUELS LLC (”Petitioner") is the real party-in-interest.
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`Related matters (37 C.F.R. § 42.8(b)(2)): Administrative Matters: US.
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`Patent No. 8,273,565 issued from US. Patent Appl. No. 13/246,693,
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`filed
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`September 27, 2011. The '693 application is a division of US. Patent Appl. No.
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`l3/228,342, filed September 8, 2011, now US. Patent No. 8,071,358; and of US.
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`Patent Appl. No. 12/953,884, filed November 24, 2010, now US. Patent No.
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`8,017,376. The '376 patent
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`is currently under Inter Partes Reexamination as
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`Control No. 95/001,870.
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`Judicial Matters: Gevo asserted the '376 patent against Butamax in Gevo,
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`Inc. v. ButamaxTM Advanced Biofuels LLC, et al., No. 11-54(SLR)(D. Del. Aug.
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`11, 2011). Final judgment was entered on August 8, 2013 in that case. Gevo
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`asserted the '565 patent against Butamax in Gevo, Inc. v. ButamaxTM Advanced
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`Biofuels LLC, et al., No. 12-1202(SLR)(D. Del. Sept. 25, 2011). In addition,
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`Butamax filed for declaratory judgment of invalidity of the '565 patent
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`in
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`ButamaxTM Advanced Biofuels LLC, et al. v. Gevo, Inc., No. 12-1201(SLF:)(D.
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`Del. Sept. 25, 2011). Gevo moved to voluntarily dismiss with prejudice all claims
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`by Gevo against Butamax and DuPont in the 12—1202 and 12-1201 actions on
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`August 7, 2013. On the same day, ButamaX moved to voluntarily dismiss without
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`prejudice all claims, defenses and counterclaims of Butamax and DuPont against
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`Gevo in the 12-1202 and 12-1201 actions. The court closed both actions on
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`August 9, 2013.
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`The Federal Circuit has consistently interpreted the effect of voluntary
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`dismissal without as leaving the parties as though the action has never been
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`brought. Graves v. Principz', 294 F.3d 1350, 1356 (Fed. Cir. 2002) ("The dismissal
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`of an action without prejudice leaves the parties as though the action had never
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`been brought"); Bonneville Associates, Ltd. Partnership v. Baram, 165 F.3d 1360,
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`1364 (Fed. Cir. 1999); accord, Wright, Miller, Kane, and Marcus, 9 Federal Prac.
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`& Proc. Civ. § 2367 (3d. ed.) ("[A]s numerous federal courts have made clear, a
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`voluntary dismissal without prejudice under Rule 41(a) leaves the situation as if
`
`the action never had been filed") (footnote omitted). Accordingly, Butamax’s
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`voluntary dismissal without prejudice of the earlier 12-1202 and 12-1201 actions
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`nullifies the effect of Petitioner’s request for declaratory judgment of invalidity.
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`See, e. g, IPR2013-00122, Paper No. 17 at 10 (“we conclude the dismissal of the
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`declaratory judgment [of invalidity] action without prejudice
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`does not trigger
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`the statutory bar prohibiting under 35 U.S.C. § 315(a) [petitioner] from filing a
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`petition for an inter partes review”). As such, Petitioner is not barred or estopped
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`from requesting [PR of any claim of the '565 patent.
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`Designation of lead and back-up counsel (37 C.F.R. § 42.8(b)(3)):
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`
`Lead Counsei
`I
`Back-Up Counsel
`
`Deborah A. Sterling (Reg. No. 62,732)
`Peter A. Jackman (Reg. No. 45,986)
`STERNE, KESSLER, GOLDSTEIN & Fox
`STERNE, KESSLER, GOLDSTEIN & Fox
`P.L.L.C.
`P.L.L.C.
`
`
`
`1 100 New York Avenue, NW
`Washington, DC 20005
`202.772.8582 (telephone)
`202.371.2540 (facsimile)
`pj ackman—PTAB@skgf.com
`
`
`
`1100 New York Avenue, NW
`I Washington, DC 20005
`202.772.8501 (telephone)
`202.371.2540 (facsimile)
`dsterlin-PTABngkgfcom
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`Notice of service (37 C.F.E. § 42.8(b)(4)): Please direct all correspondence
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`to lead counsel at the above address. Petitioner consents to email service at:
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`dsterlin—PTAB @skgficom and pj ackman—PTAB@skgf.com.
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`iV. GROUNES FOR STANBING (37 C.F.R. § 423049))
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`Petitioner certifies that (1) the '565 patent is available for IPR; and (2)
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`Petitioner is not barred or estopped from requesting IPR of any claim of the '565
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`patent on the grounds identified in this Petition.
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`V.
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`PROCEDURAL STATEMENTS
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`This Petition is
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`filed in accordance with 37 C.F.R.
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`§ 42.106(a).
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`Concurrently filed are a Power of Attorney and Exhibit List under 37 C.F.R.
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`§ 42.10(b) and § 42.63(e), respectively. The required fee is paid through online
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`credit card payment. The USPTO is authorized to charge any fee deficiency, or
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`credit any overpayment, to Deposit Acct. No. 19-003 6.
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`v1.
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`STATEMENT OF THE PRECISE RELIEF REQUESTEB AND THE
`REASONS THEREFQR (37 C.F.R. § 42.104(b))
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`Petitioner respectfully requests IPR under 35 U.S.C. §§ 311-319 and 37
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`CPR. §§ 42.1-.80 and 42100-42123, and the cancellation of claims 1-19 of the
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`'565 patent as unpatentable under 35 U.S.C. §§ 102 and 103, as set forth herein.
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`A.
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`The '565 patent
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`The '565 patent issued on September 25, 2012, and asserts its earliest
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`priority claim to November 24, 2009. According to the PTO's electronic-
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`assignment records, Gevo owns the '565 patent by assignment. The '565 patent
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`specification is generally directed towards
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`"recombinant microorganisms
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`comprising
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`one
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`or more
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`dihydroxyacid
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`dehydratase
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`(DHAD)—requiring
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`biosynthetic pathways and methods of using said recombinant microorganisms to
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`produce beneficial metabolites derived from said DHAD-requiring biosynthetic
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`pathways." (BMXIOOl , Abstract.)
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`B.
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`Person of ordinary skill in the art
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`A POSA is presumed to be aware of all pertinent art,
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`thinks along
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`conventional wisdom in the art, and is a person of ordinary creativity. With
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`respect to the '565 patent, a POSA typically would have a PhD.
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`in the life
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`sciences or a similar related discipline, and have familiarity,
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`training, and
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`experience in molecular biology, microbial genetics and/or microbial metabolism.
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`Alternatively, a POSA typically would have at least a scientific background such
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`as a Bachelor's degree in the life sciences (e.g., biology, microbiology, molecular
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`biology or biochemistry) or a similar related discipline, and have substantial
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`familiarity,
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`training, and experience in molecular biology, microbial genetics
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`and/or microbial metabolism.
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`C.
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`Claim construction
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`Unless otherwise construed herein, the terms of claims 1-19 are to be given
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`their broadest reasonable interpretation, as understood by a POSA in view of the
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`'565 patent's specification. See 37 C.F.R. § 42.100(b).
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`1.
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`"Inactivated"
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`Claim 1 recites a "recombinant yeast microorganism .
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`.
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`. engineered to
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`comprise at least one inactivated monothiol glutaredoxin .
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`.
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`.
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`." BMXlOOl 91:15-
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`26. The term "inactivated" is not defined in the '565 patent specification.
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`However, the Examiner-Initiated Interview Summary dated May 17, 2012 in the
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`'693 application indicates that "[t]he Applicants noted that
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`the meaning of
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`'inactivate' is to render inactive so that GRX3 and GRX4 protein have no activity
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`thereof" in contrast
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`to partially functional GRX3 and GRX4 proteins. File
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`Wrapper for the '693 application, Examiner-Initiated Interview Summary dated
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`May 17, 2012 (BMX1012). As such, "inactivated" in View of the Interview
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`Summary should be construed to mean that the GRX3 and/or GRX4 protein lacks
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`all activity and excludes GRX3 and/or GRX4 proteins having reduced, attenuated
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`or partial activities.1 BMXIOOZ at ‘30 Furthermore, the inactivated GRX3 and/or
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`
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`1 A patent owner is deemed to acquiesce to an Examiner's claim construction
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`when the patentee fails to comment on the construction and that construction
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`simply repeats arguments made by the patent owner during prosecution. See, e.g.,
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`ACCO Brands, Inc. v. Micro Security Devices, Inc, 346 F.3d 1075 (Fed. Cir.
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`2003). Here, Gevo has not challenged the PTO's claim construction of the term
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`

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`GRX4 protein is not restricted in the claims by any use or function associated with
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`the claimed yeast. Accordingly, given the broadest reasonable construction, any
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`inactivated GRX3 and/or GRX4 protein is encompassed by the claims regardless
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`of whether the inactivation has any effect or not, as long as the inactivated GRX3
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`and/or GRX4 result from the one or more nucleotide deletions,
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`insertions, or
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`combinations of deletions and insertions in the corresponding endogenous gene as
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`recited in claim 1 of the '565 patent.
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`2.
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`"Engineered" recombinant yeast microorganisms comprising
`inactivated GRX3 and/or GRX4 protein that "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"
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`No claim in the '565 patent specifies which, if any, nucleotides may be
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`deleted from or
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`inserted into an endogenous gene encoding a monothiol
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`glutaredoxin in order to produce inactivated GRX3 and/or GRX4 proteins. Given
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`their broadest reasonable interpretation, then, the claims encompass any deletion
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`of one or more nucleotides, any insertion of one or more nucleotides, or any
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`"inactivated", nor can it. The PTO's claim construction mirrors that which Gevo
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`proposed in an Examiner Interview. Now that the '5 65 patent has issued, Gevo has
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`foregone its opportunity to challenge the Examiner's construction. See ACCO, 346
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`F.3d 1078-79. Thus, Gevo has acquiesced to the Examiner's claim construction.
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`combination of any deletion and any insertion of one or more nucleotides in an
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`endogenous yeast GRX3 and/or GRX4 gene that results in any "inactivated"
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`GRX3 and/or GRX4 protein, in which the protein is not expressed or is expressed
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`in a completely non—fianctional form.
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`In the second Office Action in the '693 application dated May 1, 2012, the
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`Examiner rejected claims reciting deletions, insertions and combinations thereof in
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`regulatory regions as lacking written description and enablement under 35 U.S.C.
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`§ 112, $11. See File Wrapper for the '693 application (BMX1012), Office Action
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`dated May 1, 2012 at pp. 37. In Applicants' response dated May 8, 2012,
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`recitation of regulatory regions was deleted. See BMX1012, Amendment under 37
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`CFR§ 1.116 dated May 8, 2012 at p. 2.
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`Thus, while the claimed deletions, insertions, or combinations of deletions
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`and insertions that result in inactivation of GRX3 and/or GRX4 protein do not
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`occur in the regulatory regions associated with the endogenous genes, they are not
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`otherwise limited by the '565 patent claims to any portion of the coding regions of
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`the endogenous GRX3 and/or GRX4 genes. As such, given their broadest
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`reasonable construction in light of the specification and prosecution history, the
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`claims encompass any deletion of one or more nucleotides, any insertion of one or
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`more nucleotides, or any combination of any deletion and any insertion of one or
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`more nucleotides in an endogenous yeast GRX3 and/or GRX4 gene that results in
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`any "inactivated" GRX3 and/or GRX4 protein, such that
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`the protein is not
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`expressed or is expressed in a completely non-functional form, so long as the
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`deletions, insertions, or combinations of deletions and insertions that result in
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`inactivation of GRX3 and/or GRX4 protein do not occur in the regulatory regions
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`associated with the endogenous genes. BMX1002 at i.127.
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`3.
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`Yeast genera/species
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`Claim 1 of the '565 patent does not specify a genera of recombinant yeast
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`and thus encompasses every yeast genera. Dependent claims 2—16 and 19 also
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`must be construed to encompass every yeast genera since they depend directly or
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`indirectly from claim 1 and do not specify a genera of recombinant yeast. Only
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`claims 17 (yeast genera) and 18 (yeast species) further limit the origin of the
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`recombinant yeast. Claims 1-16 and 19 must therefore encompass at least these
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`yeast genera and species. 35 U.S.C. § 112, fourth para; and Fromson v. Anitec
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`Printing Plates, Inc., 132 F.3d 1437, 1445 (Fed. Cir. 1997) overruled on other
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`grounds by Cybor Corp. v. Fas Techs., 138 F.3d 1448, 1456 (Fed. Cir. 1998).
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`4.
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`DHAD localization
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`Independent claim 1, from which claims 2-19 depend directly or indirectly,
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`generically recites "dihydroxy acid dehydratase (DHAD)" without specifying
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`Where in the cell the DHAD is localized. Dependent claims 11 and 12 specify that
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`the DHAD is localized in the cytosol and in the mitochondria, respectively. Thus,
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`independent claim 1 must be construed to encompass yeast overexpressing a
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`DHAD that is generic with respect to the DHAD's location in the cell (e.g.,
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`including a DHAD that may be localized in either
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`the cytosol or
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`the
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`mitochondria). See 35 U.S.C. § 112, fourth para. and Fromson, 132 F.3d at 1445.
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`D.
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`Identification of Challenge (37 C.F.R. § 42.E04E(b))
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`IPR of the challenged claims of the '565 patent is requested on the grounds
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`for unpatentability listed in the index below. Per 37 CPR. § 42.6(d), copies of the
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`references
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`are
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`filed herewith.
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`In support of the proposed grounds
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`for
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`unpatentability, this Petition is accompanied by the declaration of Dr. Dennis J.
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`Thiele (BMXIOOZ), an expert
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`in the fields of molecular biology and yeast
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`genetics, which explains what the art would have conveyed to a POSA.
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`
`Index of References
`Claims
`35 U.S.C.
`Ground
`
`F—
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`1
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`§102(e)
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`1-8 and
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`1149
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`
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`
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`Flint BMX1003
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`(
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`)
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`
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`1-4, 6-8 Anthony (BMX1005) in View of Puig
`§103(a)2 and11—19 (BMX1006)andOjeda(Bl\/IX1007)
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`
`
`
`
`Anthony (BMX1005) in View of Puig
`(BMX1006), Ojeda (BMX1007) and further
`5
`§ 103(a)
`3
`in View of the '3 76 publication (BMX1015)
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`Anthony (BMX1005) in View of Puig
`(BMX1006) and Ojeda (BMX1007) and
`9
`§ 103(a)
`4
`further in View of van Maris (BMXl 008)
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`5
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`§ 103(a)
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`10
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`Anthony (BMX1005) in View of Puig
`(BMX1006) and Ojeda (BMX1007) and
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`
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`further in View of Overkamp (BMX1009)
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`1.
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`Ground 1: claims 1—8 and 11-19 are anticipated by Flint
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`As discussed below, the '565 patent claims are not entitled to claim priority
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`benefit prior to November 24, 2010. PCT Appl. Publ. No. WO 201 1/ 1033000 A2
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`("Flint") (BMX1003) was filed by another on February 17, 2011, published in
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`English under Article 21(2) on August 25, 2011, designates the U.S., and claims
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`priority to U.S. Prov. Appl. No. 61/305,333 ("the '333 application") (BMXlOO4),
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`filed February 17, 2010. Flint and the '333 application disclose each and every
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`limitation of claims 1-8 and 11-19 of the ’565 patent. Thus, Flint qualifies as prior
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`art to the claims of the '565 patent under 35 U.S.C. § 102(e) as of the '333
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`application's February 17, 2010 filing date. Because Flint anticipates claims 1-8
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`and 11-19, it is reasonably likely that Petitioner will prevail with regard to at least
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`one challenged claim on the basis of Ground 1.
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`(a) None of claims 1-19 is entitled to the benefit of the filing dates of
`the '952 or '209 provisional applications
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`Claims 1—19 of the '565 patent are not entitled to the benefit of the filing
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`dates of U.S. Prov. Appl. Nos. 61/263,952 or 61/350,209 ("the '952 and '209
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`provisional applications") (BMXlOlO and BMXlOl 1, respectively) because each
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`provisional application fails to describe the recombinant yeast claimed in the '565
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`patent as required by 35 U.S.C. § 112, first para. See 35 U.S.C. § 112, first para.
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`and 35 U.S.C. § 119(e). For example, the '952 and '209 provisional applications
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`fail to adequately describe the full scope of claim 1, which as discussed in Vl.C.,
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`broadly encompasses any yeast microorganism comprising a recombinantly
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`overexpressed polynucleotide encoding any DHAD and engineered to comprise
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`any inactivated GRX3 and/er GRX4 protein, and which further broadly
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`encompasses: ( 1) any deletion of one or more nucleotides in the coding region of
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`an endogenous GRX3 and/or GRX4 gene, or (2) any insertion of one or more
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`nucleotides into the coding region of an endogenous GRX3 and/or GRX4 gene, or
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`(3) any combination of such deletions and insertions, that result in the inactivated
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`protein, as discussed below. Because claims 1-19 are not entitled to a priority date
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`prior to November 24, 2010, intervening art such as Flint, discussed below with
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`regard to anticipation, is available as prior art under 35 U.S.C. § 102(e).
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`(i)
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`The provisional applications do not describe the full scope of
`inactivated GRX3 and/or GRX4 of claims 1-19 of the '565 patent
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`As discussed in VI.C.2, each of claims 1-19 of the '565 patent is broadly
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`directed to recombinant yeast microorganisms or a method of using a recombinant
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`yeast microorganism that,
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`inter alia, has been engineered to comprise an
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`"inactivated" GRX3 and/or GRX4 protein. Yet, strikingly, the bulk of the '952 and
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`'209 provisional applications is directed n_ot to inactivation of GRX3 and/or GRX4
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`in order to increase overexpressed DHAD activity.
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`Instead,
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`the provisional
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`applications are noticeably directed to expression and overexpression of GRX3
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`and/or GRX4 in order to increase DHAD activity.2 For example, i§[‘l][00155] and
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`[00156] of the '952 application and ‘[‘][00179] and [00180] of the '209 provisional
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`application, which are under the sections describing ways to enhance DHAD
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`activity, discuss alleged knowledge regarding GRX3 and GRX4 in yeast and list
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`nine specific "embodiments" associated with GRX3 and/or GRX4 expression. But
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`eight of those nine embodiments are directed to overexpression of GRX3 and/or
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`GRX4.3 Indeed, the header of the section including these GRX3/4 embodiments in
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`2 See, e.g, BMX1010,
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`‘,[‘1[[0023] and [00116] and BMX1011, 11'] [0023] and
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`[00122], disclosing GRX3 and GRX4 as a "chaperone protein" that when
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`expressed can assist the folding of a cytosolically active DHAD; BMX1010 and
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`BMX1011, [[0028], disclosing overexpression of one or more genes including
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`GRX3 and GRX4 as leading to increased iron levels in the cytosol and
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`mitochondria for availability in producing F e—S cluster-containing proteins in the
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`cytosol, which BMX1010 further discloses includes cytosolic DHAD; BMX1010,
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`if [0030] and [00189] and BMX1011, fi[0033] and [00212], disclosing over—
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`expression of GRX4 for increasing glutathione levels in the cytosol. See also,
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`BMX1010 at ‘Jfi[00154]-[00156], [00158], claims 33, 55, and 66, and BMX1011
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`at ‘flI[00178]-[00182], claims 33, 55, and 66.
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`3 (1) "er3 is overexpressed," (2) "er4 is overexpressed,” (3) "er3 and er4
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`the '209 provisional application — the later-filed of the two provisional
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`applications —— is entitled "Enhancing DHAD Activity by Increased GRX3/GRX4
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`Activity and/or Expression." So, even at
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`the later priority date of the '209
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`provisional application, the Applicants considered increasing GRX3 and GRX4
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`expression to be the focus of any change in GRX3 and GRX4 activity, and not
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`deletion or "inactivation." See BMX1002 at fl25.
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`Furthermore, 11[00156] of the '952 provisional application and ‘l[00180] of
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`the '209 provisional application state that the embodiments disclosed in those
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`paragraphs "can also be combined with increases in the exteacellular
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`iron
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`concentration to provide increased iron in the cytosol or mitochondria of the cell."
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`As such, ‘fl[00156] of the '952 application and ‘fi[00180] of the '209 application
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`confusingly describe achieving the same effect of increased iron in the cytosol or
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`mitochondria as a result of either "overexpression" or "deletion or attenuation" of
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`GRX3 and/or GRX4. This perplexing disclosure makes clear that the Applicants
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`are overexpressed," (4) "er3, er4, or er3 and er4 are deleted or attenuated,"
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`(5) "er3 and Aftl are overexpressed," (6) "er4 and Aftl are overexpressed,"
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`(7) "er3 and Aft2 are overexpressed," (8) "er4 and Aft2 are overexpressed,"
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`and (9) "One or both of: Aftl, Aft2 is overexpressed either alone or
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`in
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`combination with: er3 or er4." BMXlOlO at ‘fl[00156]; BMXlOll at f([00180].
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`had not yet settled on what was believed to be their invention when filing the
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`provisional applications. BMXlOOZ at 1126.
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`Indeed,
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`there are no examples,
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`working or otherwise,
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`to elucidate whether
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`the Applicants considered (1)
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`"overexpression" of GRX3 and/or GRX4, or (ii) "deletion or attenuation" of
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`GRX3 and/or GRX4 to be the invention here. In this case, the law is clear, "[a]
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`'mere wish or plan' for obtaining the claimed invention is not adequate written
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`description." Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353, 1362
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`(Fed. Cir. 2011)(citing Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d
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`1341, 1348 (Fed. Cir. 2011)).
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`In sum, the provisional applications indicate a lack of possession of the
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`subject matter of the '565 patent claims, because the Applicants appeared to lack
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`an understanding of the effects of GRX3 and/or GRX4 activity and were simply
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`attempting to encompass all possible effects in the disclosure. Even if Applicants
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`had shown any indication that they possessed a method of using a recombinant
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`yeast microorganism that,
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`inter alia, has been engineered to comprise an
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`"inactivated" GRX3 and/0r GRX4 protein, which they did not,
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`there is no
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`evidence that Applicants possessed the full scope of possible "inactivated" GRX3
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`and/or GRX4 proteins encompassed by the '5 65 patent claims.
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`As discussed in VI.C.1, a yeast comprising an "inactivated" GRX3 and/or
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`GRX4 protein in claims 1-19 of the '565 patent would include: (1) a yeast in
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`which the GRX3 and/or GRX4 proteins are not expressed, (2) a yeast in which
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`GRX3 and/or GRX4 proteins are expressed in completely non-functional forms,
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`and (3) a yeast in which one of GRX3 or GRX4 protein is not expressed, while the
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`other is expressed in a completely non-functional form. See Bl‘va1002 at ‘J27. Yet
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`the '952 and '209 provisional applications fail to adequately describe this genus.
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`For example,
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`the term "inactivated" is not defined in the provisional
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`applications, and expression of GRX3 and/or GRX4 proteins in completely non-
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`functional forms is not described. See BMX1002 at {1129- There are no working
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`examples of recombinant yeast in which GRX3 and/or GRX4 are deleted. Id. At
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`best,
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`the '952 provisional application sparsely discloses that yeast may be
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`engineered to "delete" or "attenuate" GRX3 and/or GRX4 genes, while the '209
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`provisional application sparsely discloses that yeast may be engineered to "delete,"
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`"reduce," or "attenuate" GRX3 and/or GRX4 genes.4 Id. Because "inactivated" in
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`the '565 patent claims must be construed as absence of all GRX3 and/or GRX4
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`activity in view of the Examiner-Initiated Interview Summary dated May 17, 2012
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`4 BMX1010 at fl[0028],
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`[00154]-[00158], and claim 56, and BMX1011 at
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`fl[00178], [00180]—[00182], and claim 56, generically disclose deletion and/or
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`attenuation of GRX3 and/or GRX4 genes. BMX1010 at ifi[0031] also generically
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`discloses deletion, reduction, and/or attenuation of GRX3 and/or GRX4.
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`in the File Wrapper of the '693 application (BMX1012), disclosure regarding yeast
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`that have been engineered to "reduce" or "attenuate" genes would not support the
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`scope of the claims, because such reductions and attenuations would be
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`understood to accomplish less than complete inactivation of all GRX3 and/or
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`GRX4 activities. See BMX1002 at EH30.
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`Furthermore, generic disclosure of yeast engineered to "delete" GRX3
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`and/or GRX4 genes would be understood by a POSA to only encompass, at best, a
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`complete deletion of the GRX3 and/or GRX4 genes, such that the corresponding
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`proteins are not expressed. See BMX1002 at {31. For example,
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`the '952
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`provisional application at
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`‘fl[00268] and the '209 provisional application at
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`{[00299] disclose that "when expression is to be repressed or eliminated, the gene
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`for the relevant enzyme, protein or RNA can be eliminated by known deletion
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`techniques." As such, the '952 and '209 provisional applications, at best, disclose
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`absence of GRX3 and/or GRX4 protein expression by complete deletion of the
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`endogenous genes. However, the claims of the '5 65 are not so limited, and the '952
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`and '209 provisional applications do not disclose expression of GRX3 and/or
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`GRX4 proteins that are non-functional as a result of partial deletions of the
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`endogenous genes. See BMX1002 at ifJ32.
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`Given the complete absence of any specific disclosure in the '952 and '209
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`provisional applications for
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`inactivated GRX3 and/or GRX4 resulting from
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`anything less than complete deletion of the genes and given the clear focus of the
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`provisional applications on overexpression of GRX3 and/or GRX4, a POSA
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`would not have understood the Applicants to be in possession of the broadly
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`claimed inactivated GRX3 and/or GRX4 proteins. See BMX1002 at $732 and 33.
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`Thus, in accordance with cases such as Boston Scientific and Centocor, the mere
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`wish or plan set forth in the '952 and '209 provisional applications does not
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`provide written description support
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`for claims 1-19 of the '565 patent.
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`Accordingly, claims 1-19 are not entitled to priority ben