throbber
Trials@uspto.gov
`571.272.7822
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Paper No. 33
`
` Filed: March 3, 2015
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BUTAMAXTM ADVANCED BIOFUELS LLC,
`Petitioner,
`
`v.
`
`GEVO, INC.,
`Patent Owner.
`____________
`
`Case IPR2013-00539
`Patent 8,273,565 B2
`____________
`
`
`Before RAMA G. ELLURU, CHRISTOPHER L. CRUMBLEY, and
`KERRY BEGLEY, Administrative Patent Judges.
`
`BEGLEY, Administrative Patent Judge.
`
`
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`
`
`ButamaxTM Advanced Biofuels LLC (“Petitioner”) filed a Petition
`
`requesting inter partes review of claims 1–19 of U.S. Patent No. 8,273,565
`
`B2 (Ex. 1001, “the ’565 patent”). Paper 4 (“Pet.”). Pursuant to 35 U.S.C.
`
`§ 314(a), we determined the Petition showed a reasonable likelihood that
`
`Petitioner would prevail in establishing the unpatentability of claims 1–9 and
`
`11–19 of the ’565 patent, and instituted an inter partes review of these
`
`
`
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`claims on certain asserted grounds of unpatentability. Paper 9 (“Inst. Dec.”).
`
`We, however, did not institute review of claim 10 of the ’565 patent,
`
`because we determined the Petition did not show a reasonable likelihood that
`
`Petitioner would prevail in establishing the claim to be unpatentable. Id. at
`
`27–29.
`
`Patent Owner Gevo, Inc. (“Patent Owner”) then filed a Patent Owner
`
`Response. Paper 19 (“PO Resp.”). Petitioner filed a Reply to Patent
`
`Owner’s Response. Paper 21 (“Reply”).
`
`An oral hearing was held on October 28, 2014, pursuant to a request
`
`by Petitioner. Paper 32 (“Tr.”); Petitioner Butamax’s Request for Oral
`
`Argument (Paper 23); Order – Trial Hearing (Paper 24), at 1. During the
`
`oral hearing, Petitioner presented argument; Patent Owner rested on its
`
`arguments in the Patent Owner Response. Tr. 40:3–13; see id. at 39:7–
`
`42:18; Order – Conduct of the Proceeding (Paper 25).
`
`We issue this Final Written Decision pursuant to 35 U.S.C. § 318(a)
`
`and 37 C.F.R. § 42.73. For the reasons that follow, we determine Petitioner
`
`has shown by a preponderance of the evidence that claims 1–9 and 11–19 of
`
`the ’565 patent are unpatentable.
`
`I. BACKGROUND
`
`A. THE ’565 PATENT
`
`The ’565 patent, titled “Methods of Increasing Dihydroxy Acid
`
`Dehydratase Activity to Improve Production of Fuels, Chemicals, and
`
`Amino Acids,” is directed to recombinant yeast microorganisms with
`
`increased activity of dihydroxy acid dehydratase (“DHAD”). Ex. 1001,
`
`[57], 1:29–2:25. DHAD is an enzyme that catalyzes steps in various
`
`biosynthetic pathways that produce metabolites, such as isobutanol, a
`
`
`
`2
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`common fuel additive. Id. at [57], 1:46–66, Fig. 1. Increased DHAD
`
`activity is favorable for producing these metabolites. Id. at 1:65–2:20,
`
`24:31–33. The patent also discloses methods of producing such metabolites
`
`by cultivating the disclosed recombinant microorganisms in a culture
`
`medium containing a carbon source feedstock. Id. at [57], 8:55–63.
`
`The specification of the ’565 patent discloses recombinant
`
`microorganisms with increased DHAD activity resulting from alterations in
`
`the regulation, expression, or activity of either or both the GRX3 and GRX4
`
`genes, which encode the proteins monothiol glutaredoxin-3 (“Grx3”) and
`
`monothiol glutaredoxin-4 (“Grx4”), respectively. Id. at 24:36–50; see id. at
`
`23:30–57, 24:1–30. For example, in one embodiment, the Grx3 protein, the
`
`Grx4 protein, or both the Grx3 and Grx4 proteins are “deleted or
`
`attenuated.” Id. at 24:9–11. The specification also discloses recombinant
`
`microorganisms with improved DHAD activity resulting from
`
`overexpression of either or both the transcriptional activator genes AFT1 and
`
`AFT2, which encode activator of ferrous transport (“Aft”) proteins, Aft1 and
`
`Aft2, respectively. Id. at 2:9–25, 4:14–26, 15:49–54. The DHAD in these
`
`embodiments may be localized in either the cytosol or the mitochondria of
`
`the microorganisms. Id. at 3:30–46, 16:33–34, 24:36–45. Further, the
`
`recombinant microorganisms may be one of various disclosed yeast genera
`
`and species, including Saccharomyces cerevisiae. See id. at 7:49–8:54.
`
`B. ILLUSTRATIVE CLAIM
`
`Claim 1, the only independent claim of the ’565 patent, is illustrative
`
`of the challenged claims:
`
`1. A recombinant yeast microorganism comprising a
`recombinantly overexpressed polynucleotide encoding a
`dihydroxy acid dehydratase (DHAD),
`
`
`
`3
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`
`wherein said recombinant yeast microorganism is
`engineered to comprise at least one inactivated monothiol
`glutaredoxin selected from the group consisting of
`monothiol glutaredoxin-3 (GRX3) and monothiol
`glutaredoxin-4 (GRX4),
`
`and wherein said inactivated monothiol glutaredoxin results
`from the deletion of one or more nucleotides of an
`endogenous gene encoding said monothiol glutaredoxin, the
`insertion of one or more nucleotides into an endogenous
`gene encoding said monothiol glutaredoxin, or combinations
`thereof.
`
`Id. at 91:15–26 (line breaks added).
`
`C. INSTITUTED GROUNDS OF UNPATENTABILITY
`
`We instituted inter partes review of the ’565 patent on the following
`
`grounds of unpatentability asserted in the Petition. Inst. Dec. 29.
`
`Basis
`Claim[s]
`1–4, 6–8, and 11–19 § 102(e) Flint
`1–4, 6–8, 11, 13, 14,
`§ 103(a) Anthony, Puig, and Ojeda
`and 16–19
`5
`9
`
`§ 103(a) Anthony, Puig, Ojeda, and Li
`§ 103(a) Anthony, Puig, Ojeda, and van Maris
`
`Reference[s]
`
`These instituted grounds rely on the following prior art references:
`
`Anthony US 2010/0081179 A1
`Li
`US 2009/0163376 A1
`Flint
`WO 2011/103300 A2
`
`Apr. 1, 2010
`June 25, 2009
`Aug. 25, 2011
`
`Ex. 1005
`Ex. 1015
`Ex. 1003
`
`
`Antonius J. A. van Maris et al., Directed Evolution of Pyruvate
`Decarboxylase-Negative Saccharomyces cerevisiae, Yielding a C2-
`Independent, Glucose-Tolerant, and Pyruvate-Hyperproducing Yeast, 70
`APPLIED & ENVTL. MICROBIOLOGY 159 (2004). (Ex. 1008, “van Maris.”)
`
`Sergi Puig et al., Coordinated Remodeling of Cellular Metabolism During
`Iron Deficiency Through Targeted mRNA Degradation, 120 CELL 99 (2005).
`(Ex. 1006, “Puig.”)
`
`
`
`
`4
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`Luis Ojeda et al., Role of Glutaredoxin-3 and Glutaredoxin-4 in the Iron
`Regulation of the Aft1 Transcriptional Activator in Saccharomyces
`cerevisiae, 281 J. BIOLOGICAL CHEMISTRY 17661 (2006). (Ex. 1007,
`“Ojeda.”)
`
`II. ANALYSIS
`A. LEVEL OF ORDINARY SKILL IN THE ART
`
`
`
`We begin our analysis by addressing the level of ordinary skill in the
`
`art, which is relevant to the governing standards we apply in the remainder
`
`of our analysis. Petitioner proposes a standard for one of ordinary skill in
`
`the art. Pet. 6; see Ex. 1002 (Decl. of Dennis J. Thiele, Ph.D.) ¶ 17. Patent
`
`Owner has not contested this proposal or proffered an alternative standard.
`
`We adopt Petitioner’s proposed standard and, therefore, determine that one
`
`of ordinary skill in the art would have had either: (1) “a Ph.D. in the life
`
`sciences or a similar related discipline, and . . . familiarity, training, and
`
`experience in molecular biology, microbial genetics and/or microbial
`
`metabolism,” or (2) “a scientific background such as a Bachelor’s degree in
`
`the life sciences (e.g., biology, microbiology, molecular biology or
`
`biochemistry) or a similar related discipline, and . . . substantial familiarity,
`
`training, and experience in molecular biology, microbial genetics and/or
`
`microbial metabolism.” Pet. 6; see Ex. 1002 ¶ 17.
`
`B. CLAIM INTERPRETATION
`
`We next address the meaning of the claims. The Board interprets
`
`claims using the “broadest reasonable construction in light of the
`
`specification of the patent in which [they] appear[].” 37 C.F.R. § 42.100(b);
`
`see In re Cuozzo Speed Techs., LLC, No. 2014-1301, 2015 WL 448667, at
`
`*5–*8 (Fed. Cir. Feb. 4, 2015). We presume a claim term carries its
`
`“ordinary and customary meaning,” which is “the meaning that the term
`
`
`
`5
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`would have to a person of ordinary skill in the art in question” at the time of
`
`the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
`
`2007). This presumption, however, is rebutted when the patentee acts as a
`
`lexicographer by giving the term a particular meaning in the specification
`
`with “reasonable clarity, deliberateness, and precision.” In re Paulsen, 30
`
`F.3d 1475, 1480 (Fed. Cir. 1994).
`
`1. “INACTIVATED”
`
`Petitioner asserts that “inactivated,” as used in the following limitation
`
`of claim 1, “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),” Ex. 1001, 91:17–21 (emphasis added), “should be
`
`construed to mean that the GRX3 and/or GRX4 protein lacks all activity and
`
`excludes GRX3 and/or GRX4 proteins having reduced, attenuated or partial
`
`activities.” Pet. 7. Petitioner supports its argument with statements in an
`
`Examiner-Initiated Interview Summary in the prosecution history of the
`
`’565 patent in which Patent Owner “noted that the meaning of ‘inactivate’ is
`
`to render inactive so that GRX3 and GRX4 protein have no activity thereof,”
`
`and the Patent Examiner “agree[d].” Id. at 7; Ex. 1012, Examiner-Initiated
`
`Interview Summary (May 17, 2012). Patent Owner has not responded to
`
`Petitioner’s assertions regarding the meaning of “inactivated” or proposed a
`
`construction for the term. See generally PO Resp.
`
`The plain and ordinary meaning of “inactivated” is having destroyed
`
`biologic activity; chemically or biologically inert; non-functional. See
`
`Ex. 3005 (The American Heritage Medical Dictionary 402 (Rev. ed. 2007))
`
`(defining “inactivate” as “[t]o render nonfunctional”); Ex. 3006 (Stedman’s
`
`
`
`6
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`Medical Dictionary 959 (28th ed., Lippincott Williams & Wilkins 2006))
`
`(defining “inactivate” as “[t]o destroy the biologic activity or the effects of
`
`an agent or substance”); Ex. 3007 (Merriam-Webster’s Collegiate
`
`Dictionary 584 (10th ed. 2000)) (defining “inactivate” as “to make inactive,”
`
`and “inactive” as “chemically” or “biologically inert”); Ex. 3008 (Dictionary
`
`of Science and Technology 1092 (Christopher Morris, ed. 1992)) (defining
`
`“inactivate” as “to render inactive; destroy the activity of”). This customary
`
`meaning, thus, requires a lack of all activity or functionality.
`
`The usage of “inactivated” and related terms in the specification of the
`
`’565 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 “inactivate” in a manner similar to “inactivated” in
`
`claim 1: “said recombinant yeast microorganism is further engineered to
`
`inactivate one or more endogenous pyruvate decarboxylase (PDC)”
`
`(claim 9) and “glycerol-3-phosphate dehydrogenase (GPD)” (claim 10).
`
`Ex. 1001, 91:58–65 (emphasis added). These claims, therefore, offer no
`
`further clarity regarding the meaning of the term. Likewise, references to
`
`the term in other portions of the specification do not define or otherwise
`
`explicate its meaning. Upon review of the record, we are not persuaded that
`
`the inventors of the ’565 patent acted as their own lexicographer to alter the
`
`ordinary and customary meaning of the term “inactivated.”
`
`Accordingly, to the extent Petitioner’s proposed construction of
`
`“inactivated” requires a “lack[ of] all activity,” we conclude that it is
`
`consistent with the plain and ordinary meaning of the term as well as its
`
`usage in the ’565 patent specification. Pet. 7. We, however, reject the
`
`remainder of Petitioner’s proffered construction, “exclud[ing] GRX3 and/or
`
`
`
`7
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`GRX4 proteins having reduced, attenuated or partial activities,” because it is
`
`directed to the scope of claim 1, rather than the meaning of the term
`
`“inactivated.” Id.
`
`For these reasons, we construed “inactivated” to mean lacking all
`
`activity or functionality in our Decision to Institute. Inst. Dec. 8–10.
`
`Neither party has challenged this construction. See generally PO Resp.;
`
`Reply. Having considered whether this construction should be changed in
`
`light of the evidence introduced during trial, we are not persuaded any
`
`modification is necessary. Therefore, we maintain our construction of
`
`“inactivated” as lacking all activity or functionality.
`
`2. OTHER CLAIM TERMS
`
`Petitioner also proposes a construction for the final limitation of claim
`
`1, asserting that the recited inserted or deleted nucleotides could not occur in
`
`“regulatory regions associated with the endogenous genes.” Pet. 8–11. In
`
`our Decision to Institute, we determined that we need not address
`
`Petitioner’s proposed construction, because whether the inserted or deleted
`
`nucleotides can occur in regulatory regions does not impact Petitioner’s
`
`asserted grounds of unpatentability. Inst. Dec. 10–11. Neither party has
`
`challenged this determination. See Reply 1; see generally PO Resp. Having
`
`considered the issue in light of the evidence adduced during trial, we are not
`
`persuaded that any modification of our determination is necessary.1
`
`
`1 The Petition also argues that claim 1 encompasses at least the yeast genera
`and species recited in dependent claims 17 and 18, and at least DHAD
`localized in either the cytosol or the mitochondria, as recited in dependent
`claims 11 and 12, respectively. Pet. 9–10. Although we agreed with
`Petitioner in our Decision to Institute, this interpretation is not necessary to
`our final decision. See Inst. Dec. 11–12; Pet. 24–25; infra n.5.
`
`
`
`8
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`
`C. INSTITUTED GROUNDS OF UNPATENTABILITY
`
`We turn to the merits of the instituted grounds of unpatentability.
`
`1. ANTICIPATION BY FLINT — CLAIMS 1–4, 6–8, AND 11–19
`
`We begin with the instituted ground asserting that claims 1–4, 6–8,
`
`and 11–19 of the ’565 patent are unpatentable under 35 U.S.C. § 102(e)2 as
`
`anticipated by Flint. Pet. 12–29; Inst. Dec. 12–18, 29. Flint, 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 (“’333
`
`provisional” or “Flint ’333 provisional”), filed on February 17, 2010.
`
`Ex. 1003, [10], [22], [30], [43]. Therefore, Flint’s earliest claimed effective
`
`filing date is February 17, 2010.
`
`The ’565 patent was filed on September 27, 2011 as a divisional of
`
`U.S. Application Serial Nos. 13/228,342, filed September 8, 2011, and
`
`12/953,884, filed November 24, 2010. Ex. 1001, [22], [62], 1:9–12. The
`
`’565 patent further claims priority to two provisional applications: U.S.
`
`Provisional Application Serial Nos. 61/350,209 (“’209 provisional”), filed
`
`June 1, 2010, and 61/263,952 (“’952 provisional”), filed November 24,
`
`2009. Id. at [60], 1:12–17.
`
`Thus, Flint—with the benefit of the filing date of the ’333 Flint
`
`provisional (February 17, 2010)—is prior art to the ’565 patent under
`
`§ 102(e) unless the ’565 patent is entitled to the benefit of the filing date of
`
`the ’952 provisional (November 24, 2009). See 35 U.S.C. § 102(e); Pet. 12.
`
`
`2 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29, 125
`Stat. 284 (2011), revised 35 U.S.C. §§ 102–103, effective March 16, 2013.
`Because the ’565 patent has an effective filing date before March 16, 2013,
`our references and citations to §§ 102–103 in this decision are to their pre-
`AIA version.
`
`
`
`9
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`Accordingly, in addition to arguing that Flint and the ’333 provisional
`
`disclose each limitation of claims 1–4, 6–8, and 11–19 of the ’565 patent,
`
`the Petition further contends that the ’565 patent claims are not entitled to
`
`the benefit of the filing date of either the ’952 provisional or the
`
`’209 provisional, because neither provides written description support for
`
`claim 1, the sole independent claim, of the ’565 patent. Pet. 12–29.
`
`In the Response, Patent Owner disputes Petitioner’s assertion that
`
`Flint is prior art to the ’565 patent, arguing that the ’565 patent is entitled to
`
`the benefit of the filing date of the ’952 provisional, because both the ’952
`
`and ’209 provisionals provide written description support for the ’565 patent
`
`claims. PO Resp. 2–3, 5–15. Patent Owner, however, does not contest that
`
`Flint and the ’333 provisional disclose each limitation of claims 1–4, 6–8,
`
`and 11–19 of the ’565 patent. See id. at 2–3, 15.
`
`We consider first whether Flint is prior art to the ’565 patent, then
`
`whether Flint’s disclosure is anticipatory.
`
`a. PRIOR ART STATUS OF FLINT
`
`In this inter partes review, Petitioner has the burden of persuasion to
`
`establish unpatentability—including “all issues relating to the status of
`
`[Flint] as prior art,” Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1576–78
`
`(Fed. Cir. 1996)—by a “preponderance of the evidence,” 35 U.S.C. § 316(e).
`
`This burden of persuasion remains with Petitioner, while the burden of
`
`production—the burden to come forward with evidence—shifts between the
`
`parties. See Tech. Licensing Corp. v. Videotek, Inc., 545 F.3d 1316, 1327–
`
`29 (Fed. Cir. 2008); Mahurkar, 79 F.3d at 1576–77; Corning Inc. v. DSM IP
`
`Assets B.V., Case IPR2013-00053, slip op. at 6–8 (PTAB May 1, 2014)
`
`(Paper 66) (“[T]hough the patent owner bears the burden of production in
`
`
`
`10
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`antedating a reference, the burden of persuasion to prove unpatentability . . .
`
`remains with the petitioner.”). Now, “with all of the evidence from both
`
`sides before [us]”—the burden of production having shifted back and forth
`
`between the parties—Petitioner bears the ultimate burden of persuasion to
`
`establish by a preponderance of the evidence that Flint is prior art to the
`
`’565 patent, including that the ’565 patent is not entitled to the benefit of the
`
`earlier filing date of the ’952 provisional. Tech. Licensing, 545 F.3d at
`
`1327–29; Mahurkar, 79 F.3d at 1578. We determine that Petitioner has met
`
`its burden, as we explain below.
`
`i. Written Description Support for the ’565 Patent Claims in the
`’952 and ’209 Provisionals
`
`Petitioner argues that claim 1 of the ’565 patent, along with its
`
`dependent claims, is not entitled to the benefit of the filing date of either the
`
`’952 or ’209 provisional based on a lack of written description support for
`
`the following limitations of the claim:
`
`wherein said recombinant yeast microorganism is
`engineered to comprise at least one inactivated monothiol
`glutaredoxin selected from the group consisting of
`monothiol glutaredoxin-3 (GRX3) and monothiol
`glutaredoxin-4 (GRX4),
`
`and wherein said inactivated monothiol glutaredoxin results
`from the deletion of one or more nucleotides of an
`endogenous gene encoding said monothiol glutaredoxin, the
`insertion of one or more nucleotides into an endogenous
`gene encoding said monothiol glutaredoxin, or combinations
`thereof.
`
`Pet. 12–24; Ex. 1001, 91:15–26. Petitioner, with supporting testimony from
`
`its expert, Dr. Dennis J. Thiele, asserts that the provisionals describe, at best,
`
`only complete deletion of endogenous GRX3 and GRX4 genes. Pet. 17–24;
`
`Ex. 1002 ¶¶ 29–49. According to Petitioner, neither provisional provides
`
`
`
`11
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`precise definitions—such as the type, location, or size—of the insertions,
`
`deletions, or insertion and deletions of nucleotides in these genes that would
`
`result in “inactivated” Grx3 and Grx4 proteins. Pet. 17–24; Ex. 1002 ¶¶ 29–
`
`49. Petitioner, therefore, urges that the “’952 and ’209 provisional
`
`applications fail to describe adequately the full scope of the broadly claimed
`
`deletions, insertions, or combinations of deletions and insertions in the
`
`endogenous GRX3 and GRX4 genes” encompassed by claim 1 of the
`
`’565 patent. Pet. 20. In response, Patent Owner “directs [our] attention” to
`
`a list of disclosures in the ’952 and ’209 provisionals, which Patent Owner
`
`argues demonstrates that the inventors were in possession of the full scope
`
`of claimed insertions and deletions of nucleotides in the GRX3 and GRX4
`
`genes as of the filing date of each provisional. PO Resp. 7–15. Patent
`
`Owner also argues that one of ordinary skill would have been familiar with
`
`gene deletions and insertions as techniques for “inactivating a gene” and,
`
`thus, Petitioner’s arguments overlook that it is not necessary to disclose in
`
`detail what was well known in the art. Id. at 13–15.
`
`A claim in a later-filed patent application is entitled to the benefit of
`
`the filing date of an earlier-filed provisional application only if the
`
`provisional application, and all applications in the chain leading back to the
`
`provisional application, satisfy the written description requirement of
`
`35 U.S.C. § 112 for the invention claimed in the later-filed application. New
`
`Railhead Mfg., L.L.C. v. Vermeer Mfg. Co., 298 F.3d 1290, 1294–97 (Fed.
`
`Cir. 2002); see 35 U.S.C. §§ 119(e)(1), 120; Hollmer v. Harari, 681 F.3d
`
`1351, 1355 (Fed. Cir. 2012). This requirement prevents an inventor from
`
`“overreaching” in a later-filed application as to the scope of what was
`
`invented at the time of the earlier-filed application by requiring that the
`
`
`
`12
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`invention be described in “such detail that . . . future claims can be
`
`determined to be encompassed within the . . . original creation.” Vas-Cath
`
`Inc. v. Mahurkar, 935 F.2d 1555, 1561 (Fed. Cir. 1991). Specifically, to
`
`satisfy the written description requirement, the disclosure of the earlier-filed
`
`application must “reasonably convey[]” to one of ordinary skill in the art
`
`that, as of the filing date sought, “the inventor had possession” of the subject
`
`matter now claimed. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
`
`1351–52 (Fed. Cir. 2010); Vas-Cath, 935 F.2d at 1563–64. The test for
`
`written description, therefore, requires “an objective inquiry into the four
`
`corners of the specification from the perspective of a person of ordinary skill
`
`in the art” to determine whether the specification “show[s] that the inventor
`
`[had] actually invented,” or possessed, each feature now included as a claim
`
`limitation. Ariad Pharm., 598 F.3d at 1351; see New Railhead Mfg., 298
`
`F.3d at 1295.
`
`The Federal Circuit has established specific requirements for written
`
`description of genus claims, i.e., claims encompassing two or more
`
`embodiments, that “use functional language to define the[ir] boundaries.”
`
`Ariad Pharm., 598 F.3d at 1349–50; see Billups-Rothenberg, Inc. v.
`
`Associated Reg’l & Univ. Pathologists, Inc., 642 F.3d 1031, 1037 (Fed. Cir.
`
`2011). Claim 1 of the ’565 patent is a functionally-defined genus claim
`
`because it recites the function, or desired or useful result, of “inactivat[ion]”
`
`of “at least one” Grx3 and Grx4 proteins, and further recites that this
`
`inactivation “results from” any one of a number of different means:
`
`“deletion of one or more nucleotides of an endogenous gene encoding” the
`
`protein, “insertion of one or more nucleotides into an endogenous gene
`
`encoding” the protein, or “combinations thereof.” Ex. 1001, 91:15–26; see
`
`
`
`13
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`Tr. 8:6–7, 11:3–4; Billups-Rothenberg, 642 F.3d at 1037; Ariad Pharm., 598
`
`F.3d at 1349–50. We, therefore, must determine whether the ’952 and
`
`’209 provisionals meet the governing standards for written description
`
`support of this genus claim.
`
`Evaluating written description support for genus claims presents the
`
`issue of whether the disclosure in the specification demonstrates that the
`
`inventor had possession of species sufficient to support a claim to the totality
`
`of the functionally-defined genus. Carnegie Mellon Univ. v. Hoffman-La
`
`Roche Inc., 541 F.3d 1115, 1126 (Fed. Cir. 2008); Ariad Pharm., 598 F.3d at
`
`1349–50. To meet the written description requirement for such claims, the
`
`specification must disclose either: (1) “a representative number of species
`
`falling within the scope of the genus,” “precise[ly] defin[ed], such as by
`
`structure, formula, chemical name, physical properties, or other properties,”
`
`or (2) “structural features common to the members of the genus.” Ariad
`
`Pharm., 598 F.3d at 1350; Carnegie Mellon, 541 F.3d at 1122–26; Regents
`
`of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566–69 (Fed. Cir.
`
`1997). A functionally-defined genus claim also can “meet the written
`
`description requirement if a reasonable structure-function correlation is
`
`established, whether by the inventor as described in the specification or
`
`known in the art at the time of the filing date.” AbbVie Deutschland GmbH
`
`& Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1301 (Fed. Cir. 2014);
`
`see Ariad Pharm., 598 F.3d at 1350. These standards are premised on the
`
`basic principle that one of ordinary skill in the art “must be able to ‘visualize
`
`or recognize the identity of the members of the genus’” upon reviewing the
`
`disclosure. Carnegie Mellon, 541 F.3d at 1124 (quoting Eli Lilly, 119 F.3d
`
`at 1569); see Ariad Pharm., 598 F.3d at 1350.
`
`
`
`14
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`
`Here, the disclosures of the ’952 and ’209 provisionals cited by the
`
`parties as relevant to claim 1 of the ’565 patent divide into two categories.
`
`One category includes disclosures regarding inserting or deleting nucleotides
`
`of genes—not specific to the GRX3 or GRX4 gene. Ex. 1010 ¶¶ 67–68, 213,
`
`229, 258–264, 268; Ex. 1011 ¶¶ 73–74, 244, 260, 289–295, 299; see Pet.
`
`20–23; PO Resp. 7–12; Reply 2–4. For example, the ’952 and ’209
`
`provisionals define “engineer” to include “inserting a polynucleotide and/or
`
`polypeptide heterologous to the microorganism and mutating a
`
`polynucleotide and/or polypeptide native to the microorganism.” Ex. 1010
`
`¶ 67; Ex. 1011 ¶ 73 (emphases added). The provisionals, in turn, define
`
`“mutation,” to include, for example, “deletions, or insertions of single or
`
`multiple residues in a polynucleotide,” or “an insertion, or a deletion of part
`
`or all of a gene.” Ex. 1010 ¶ 68; Ex. 1011 ¶ 74 (emphases added). The
`
`provisionals explain that “an engineered or modified microorganism can also
`
`include alteration, disruption, deletion, or knocking-out of a gene or
`
`polynucleotide.” Ex. 1010 ¶ 213; Ex. 1011 ¶ 244 (emphasis added). The
`
`provisionals further refer to “known deletion techniques” and include a
`
`section, titled “Genetic insertions and deletions,” which references known
`
`techniques to “introduce” or “integrat[e]” genes or “nucleic acid
`
`molecule[s]” into yeast and to “remove[]” such “introduced marker genes.”
`
`Ex. 1010 ¶¶ 258–263, 268; Ex. 1011 ¶¶ 289–294, 299.
`
`The other category includes disclosures specifically referring to
`
`deleting, attenuating, or reducing either or both the GRX3 and GRX4 genes.
`
`Ex. 1010 ¶¶ 28, 154–58, claim 56; Ex. 1011 ¶¶ 31, 178, 180–82, claim 56;
`
`see Pet. 17–24; PO Resp. 7–12; Reply 2–4. For example, the
`
`’952 provisional states that the disclosed recombinant microorganism “may
`
`
`
`15
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`be engineered to delete and/or attenuate one or more genes selected from the
`
`group consisting of GRX3 and GRX4, or homologs thereof.” Ex. 1010 ¶ 28.
`
`The later-filed ’209 provisional adds that these genes may be reduced,
`
`specifically disclosing that the microorganism “may be engineered to delete,
`
`reduce, and/or attenuate” either or both the GRX3 and GRX4 genes.
`
`Ex. 1011 ¶ 31.
`
`Petitioner, with supporting testimony from Dr. Thiele, takes the
`
`position that one of ordinary skill in the art would understand these
`
`disclosures in the ’952 and ’209 provisionals regarding reduction and
`
`attenuation of the GRX3 and GRX4 genes to accomplish “less than complete
`
`inactivation” of the corresponding protein. Pet. 17–18; Ex. 1002 ¶ 29.
`
`Patent Owner does not dispute this testimony or otherwise address the
`
`meaning of reduction or attenuation to a person of ordinary skill in the art.
`
`See PO Resp. 5–15; Reply 2. We credit Dr. Thiele’s testimony on this point
`
`and, therefore, find that the Grx3 and Grx4 proteins in yeast engineered to
`
`reduce or attenuate either or both GRX3 and GRX4 genes would not be
`
`“inactivated” within the meaning of claim 1 of the ’565 patent. Ex. 1002
`
`¶¶ 29–30; see supra Section II.B.1. Accordingly, the disclosed reduced or
`
`attenuated GRX3 and GRX4 genes do not fall within the scope of claim 1 of
`
`the ’565 patent, and do not provide written description support for the claim.
`
`As to the disclosures in the ’952 and ’209 provisionals regarding
`
`deletion of the GRX3 and GRX4 genes, Petitioner argues that one of ordinary
`
`skill would understand the disclosures directed to deleting either or both the
`
`GRX3 and GRX4 genes “to only encompass, at best, a complete deletion of
`
`the GRX3 and/or GRX4 genes.” Pet. 18–19; Ex. 1002 ¶ 31. Patent Owner
`
`contests Petitioner’s interpretation, citing to the disclosures in the
`
`
`
`16
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`provisionals regarding “a deletion of part or all of a gene.” PO Resp. 9–10,
`
`13–14 (emphasis omitted); see Ex. 1010 ¶ 68; Ex. 1011 ¶ 74. We agree with
`
`Patent Owner. Petitioner’s proposed interpretation takes an overly narrow
`
`view of the relevant disclosures that is unjustified in light of other statements
`
`in each provisional. In each, the disclosures that microorganisms may be
`
`“engineered to delete” either or both GRX3 and GRX4 genes (Ex. 1010
`
`¶¶ 28, 158; Ex. 1011 ¶¶ 31, 182 (emphasis added)) ties to the definitions of
`
`“engineer,” which “includes . . . mutati[ons]” (Ex. 1010 ¶ 67; Ex. 1011
`
`¶ 73), and “mutation,” which includes “deletions, or insertions of single or
`
`multiple residues in a polynucleotide,” or “an insertion, or a deletion of part
`
`or all of a gene” (Ex. 1010 ¶ 68; Ex. 1011 ¶ 74). Therefore, based on the
`
`express language of the provisionals, we find that one of ordinary skill in the
`
`art would understand the references to deleting either or both the GRX3 and
`
`GRX4 genes to refer to deleting “all or part” of these genes—more
`
`specifically, both complete gene deletion (deletion of all nucleotides of the
`
`gene) and partial gene deletion (deletion of only a subset of nucleotides of
`
`the gene). Even so, however, the disclosures of the ’952 and ’209
`
`provisionals fall short of the required standards for written description, for
`
`the reasons we explain below.
`
`First, the disclosures in the ’952 and ’209 provisionals do not disclose
`
`a representative number of species falling within the scope of the claimed
`
`genus and, thus, fail to show that the inventors had “conceived and described
`
`sufficient representative species encompassing the breadth of the genus” of
`
`insertions, deletions, and combinations of insertions and deletions in either
`
`or both the GRX3 or GRX4 genes that inactivate the corresponding protein.
`
`AbbVie, 759 F.3d at 1300. Starting with deletions, the ’952 and
`
`
`
`17
`
`

`

`IPR2013-00539
`Patent 8,273,565 B2
`
`’209 provisionals do reference both complete and partial deletion of the
`
`GRX3 and GRX4 genes, as we noted above. Complete deletion of the GRX3
`
`or GRX4 genes results in non-expression of the corresponding protein,
`
`making the protein “inactive,” as recited in claim 1. See Ex. 1002 ¶¶ 31–32.
`
`Based on the disclosures in the ’952 and ’209 provisionals regarding
`
`“eliminat[ion]” of genes according to “known deletion techniques” and
`
`specifically regarding “delet[ion]” of either or both GRX3 and GRX4 genes,
`
`together with Petitioner’s acknowledgement that complete deletion of the
`
`GRX3 and GRX4 genes was known in the art when the provisionals were
`
`filed, we find that the provisionals sufficiently disclose species involving
`
`complete deletion of the GRX3 gene, the GRX4 gene, and the GRX3 and
`
`GRX4 genes, which fall within the scope of claim 1. See Ex. 1010 ¶¶ 28,
`
`154–158, 268; Ex. 1011 ¶¶ 31, 178–182, 299; Ex. 1002 ¶¶ 31–32, 37, 40–
`
`

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket