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`Paper No. 32
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`Entered: February 4, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`BUTAMAX ADVANCED BIOFUELS LLC,
`Petitioner,
`v.
`GEVO, INC.,
`Patent Owner.
`
`____________
`
`Case IPR2013-00539
`Patent 8,273,565 B2
`____________
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`Held: October 28, 2014
`____________
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`
`
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`BEFORE: RAMA G. ELLURU, CHRISTOPHER L. CRUMBLEY,
`and KERRY BEGLEY, Administrative Patent Judges.
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`APPEARANCES:
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`ON BEHALF OF THE PETITIONER:
`
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`DEBORAH STERLING, ESQ., Ph.D.
`
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`PETER JACKMAN, ESQ.
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`Sterne, Kessler, Goldstein & Fox P.L.L.C.
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`1100 New York Avenue, N.W.
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`Washington, D.C. 20005
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`Case IPR2013-00539
`Patent 8,273,565 B2
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`ON BEHALF OF PATENT OWNER:
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`BRETT LUND, ESQ., MBA
`
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`Gevo, Inc.
`
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`345 Inverness Drive South
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`Building C, Suite 310
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`Englewood, Colorado 80112
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`
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`The above-entitled matter came on for hearing on Tuesday,
`October 28, 2014, commencing at 9:06 a.m., at the U.S. Patent and
`Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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` P R O C E E D I N G S
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`JUDGE CRUMBLEY: Have a seat, everyone.
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`Good morning, everyone. I appreciate the patience. This
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`morning we have our final hearing in IPR2013-00539, Butamax
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`Biofuels versus Gevo. I'm Judge Crumbley and to my right is Judge
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`Elluru, to my left is Judge Begley.
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`We will get appearances, for the Petitioner, please?
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`MS. STERLING: Good morning, my name is Deborah
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`Sterling from Sterne, Kessler, Goldstein & Fox, and this is Peter
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`Jackman with me, who is lead back-up counsel for Petitioner.
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`JUDGE CRUMBLEY: Good morning. Who do we have
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`from the Patent Owner?
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`MR. LUND: Good morning, Your Honors, Brett Lund,
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`lead counsel for Gevo.
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`JUDGE CRUMBLEY: We put this in our trial order just
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`so everybody is on the same page, everybody will have an hour,
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`Petitioner may reserve time for rebuttal at the beginning of the
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`argument. Gevo will then have an opportunity to present any
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`argument in response, and then the rebuttal time. I'm notoriously bad
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`at setting the clock with the lights up here, so unless either party
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`objects, I will use the clock on the wall and I will try to give you a
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`five-minute warning when you get close to your time. Is that all right
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`with everyone?
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`COUNSEL: Fine.
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`JUDGE CRUMBLEY: So, if nothing else, you may
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`begin when you're ready, Ms. Sterling. Are you reserving any time?
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`MS. STERLING: I will, I will reserve 20 minutes,
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`please.
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`JUDGE CRUMBLEY: Twenty?
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`MS. STERLING: Twenty, please. I brought hard copies
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`of the slides. May I approach?
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`JUDGE CRUMBLEY: Absolutely.
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`MS. STERLING: May it please the Board, really there
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`are a few issues of contention here this morning. For start, the
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`contention of priority as to whether Gevo's claims in the '565 patent
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`are entitled to claim the benefit of priority of the provisional
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`applications. Secondly, whether the art used in the combination for
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`the 103 ground teaches away from the claims, and whether there are
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`secondary considerations commensurate in scope with the claims that
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`would weigh in favor of the patentability.
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`So, we plan to talk about the three contentious issues.
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`We also understand that the Board has questions, and issues from our
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`phone conference, so we're also happy to address any of the Board's
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`questions that they have.
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`JUDGE CRUMBLEY: We always have questions.
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`MS. STERLING: So, if we can get started, go to slide 3,
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`please. If we start with ground 1, and this is the anticipation ground
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`where claims 1 to 4, 6 to 8 and 11 to 19 are anticipated by the Flint
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`reference. And Gevo doesn't contend that Flint teaches each and
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`every limitation of these claims, but the contention here lies around
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`priority date, because if Gevo was entitled to claim the benefit of the
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`provisional applications, Flint is not prior art.
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`So, if we look at the prior art, of course, lies with the
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`claims, so the next slide, this is claim 1.
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`JUDGE BEGLEY: Before we get into the priority, just
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`on the anticipatory disclosure, I have a question about claim 12. I
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`understand that you've cited paragraph 6 of Flint for that, specifically
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`a disclosure that "native yeast DHAD is located in the mitochondria."
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`Can you explain how that discloses the recombinantly overexpressed
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`DHAD being localized and located in the mitochondria?
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`MS. STERLING: Sure. Bear with me for a second.
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`JUDGE BEGLEY: Page 35 of the expert declaration.
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`It's the claim chart where paragraph 6 of Flint is cited, and I'm just
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`wondering if you could elaborate on that and explain how it discloses
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`the claim limitation.
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`MS. STERLING: Yes, I see that, and it says that native
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`yeast DHAD is localized in the mitochondria, and I guess your
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`question is would that be a recombinant yeast microorganism that's
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`recombinantly overexpressing DHAD. Is that your question?
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`JUDGE BEGLEY: Yes.
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`MS. STERLING: So, as cited in the petition, we also
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`cite to other paragraphs of the Flint reference, if I can just look at
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`those. So, here, in Flint, it talks about using yeast host cells and
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`overexpressing a yeast DHAD enzyme. This is, for example, at
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`paragraph 25 in Flint, a yeast enzyme is natively targeted to the
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`mitochondria, so expressing a yeast DHAD within a yeast
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`microorganism, it would be natively or it would be expressed in the
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`mitochondria, unless one expressed it without a mitochondrial
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`targeting sequence, but there's no indication in Flint in certain of these
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`paragraphs, example 25, for example, that the mitochondrial targeting
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`sequence was removed.
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`Does that answer your question?
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`JUDGE BEGLEY: So, if there's no indication that the
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`mitochondrial target was removed, but that doesn't teach that -- it
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`doesn't teach the opposite, I guess, is what I'm --
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`MS. STERLING: Well, DHAD is natively localized in
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`the mitochondria in yeast.
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`JUDGE BEGLEY: Yes.
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`MS. STERLING: So, if a yeast is expressing a yeast
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`DHAD, that DHAD would be targeted to the mitochondria.
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`Does that answer your question?
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`JUDGE BEGLEY: Yes.
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`MS. STERLING: Thank you. So, I'll return to priority,
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`and if we look at the claim, and we've just discussed one part of it, the
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`claim is to recombinant yeast microorganism comprising a
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`recombinantly overexpressed polynucleotide encoding a dihydroxy
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`acid dehydratase, which we will call DHAD, and then a yeast enzyme,
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`a GRX3 protein, a GRX3 or GRX4, and inactivation, which we have
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`all agreed based on claim construction is an absence of activity,
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`results from the deletion of one or more nucleotides of a gene
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`encoding of the GRX3 or 4, the insertion of one or more nucleotides
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`into that gene, or combinations thereof.
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`Looking at the provisional applications to which the '565
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`claims priority benefit, there is no disclosure of which, if any -- I'm
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`sorry, go back a slide -- which, if any, nucleotides would be inserted
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`or deleted from the gene. At best, there's one sentence that talks
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`about -- discloses that GRX3 or 4 may be deleted or attenuated. Aside
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`from that, there's other language in the specification generally related
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`to engineering, and that language -- slide 4, please -- is the language
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`that Gevo relies upon to allege their support in provisional
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`applications.
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`And we've taken the language from their -- that they've
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`quoted from the provisional applications, and this is simple language
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`just saying that engineering is mutating polynucleotide, and those
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`mutations include deletions or insertions of single or multiple
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`residues, alternating disrupting or deleting or deleting all or part of a
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`gene, but there is no indication --
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`JUDGE CRUMBLEY: Well, counsel, I just want to
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`make sure I'm clear on this. So, you don't dispute that they have
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`support for inactivating GRX3/4 by deleting one or more nucleotides?
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`MS. STERLING: The words are there.
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`JUDGE CRUMBLEY: Right.
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`MS. STERLING: I would say that does not provide
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`written description support for the full breadth of that --
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`JUDGE CRUMBLEY: So, I thought your argument was
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`that they didn't support inserting or attenuating but rather deleting is
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`disclosed. Am I mistaken on that?
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`MS. STERLING: We would say at best, deletion of all
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`of a gene would inactivate activity. And there are the words "deleting
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`all or part of a gene."
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`JUDGE CRUMBLEY: Right.
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`MS. STERLING: But the claim is much broader than
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`that, it includes inserting one nucleotide or more.
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`JUDGE CRUMBLEY: Well, once I've targeted the gene
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`for deletion, how is a person of ordinary skill in the art not also in
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`possession of inserting into that gene for inactivation purposes?
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`You've identified the gene for deletion, so I mean, a person of
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`ordinary skill would know that that gene is the target for doing other
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`things as well. And there's disclosure in the provisionals about
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`mutations, and viewpoint insertions, but I guess I'm trying to see why
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`a person of ordinary skill isn't going to make that step.
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`MS. STERLING: The -- I think maybe Eli Lilly speaks
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`to this, where the actual words themselves, deletion or insertion, even
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`if you know a gene or a protein, is not enough. Here there's a function
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`related here, it's inactivation, and there's no correlation between the
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`structure of the gene and that function that inactivation of the gene or
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`lack of activity of the gene beyond, at best, a complete gene deletion.
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`That would, of course, delete activity and there would be an inactive
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`gene protein, but as to, you know, which one or two, or more,
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`nucleotides could be inserted, deleted or both, there's no disclosure in
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`the patent that would correlate a structure-function relationship.
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`There's no discussion of similarities between GRX3s across different
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`species, there's no discussion of a, you know, an active site or a
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`binding site that may be somewhere where a person might start to
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`envision possession of these species across the full breadth of the
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`genus. And in this case --
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`JUDGE ELLURU: So, is it your position that the
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`disclosure would have to identify the specific nucleotides that have to
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`be deleted or inserted into the DHAD gene?
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`MS. STERLING: I think it would have to give it at least
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`more than what it has, you know, give it some guidance towards the
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`structure-function correlation as to where a person might start.
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`JUDGE ELLURU: And you don't think a person of
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`ordinary skill in the art would have that knowledge that if they knew
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`they were trying to delete or insert a nucleotide to inactivate the gene,
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`that they would be able to have the knowledge to figure that out?
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`MS. STERLING: Well, the knowledge to figure it out, in
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`our opinion, goes more to enablement. We're not saying that the
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`person couldn't sit down and start screening through nucleotides at a
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`time and working through techniques that were known in the art, but
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`just because someone can take this teaching and go and then start
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`screening and may be able to arrive at a deleted or an attenuated
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`GRX3 that would involve deleting or inserting one or more
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`nucleotides, and maybe they could get there without undue
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`experimentation, but that's the point here is whether the inventors had
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`possession, it's a written description issue that we see here.
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`JUDGE ELLURU: That's my point. That is my point. I
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`mean, it does -- the disclosure does discuss inactivating via insertions
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`and deletions.
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`MS. STERLING: With no guidance as to where those
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`insertions or deletions may be, and the art of record and the art that
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`was available, yes, the sequence was available, but the only teachings
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`of attenuating GRX3 or GRX4 activity known at the time in the art
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`was a complete gene deletion.
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`JUDGE CRUMBLEY: It sounds to me, to go off my
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`colleague's question here, it sounds to me like you're making the
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`enablement argument, you're saying a person of ordinary skill doesn't
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`know how to implement insertion because you don't tell them, you
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`know, what particular gene to insert it into.
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`MS. STERLING: I'm saying that the inventors didn't
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`know a specific insertion or deletion that could be made. If you think
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`of the myriad combinations here, these proteins have about 750 to 800
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`amino acids or nucleotides. So, if you think of a combination of
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`inserting one or more is 1 to 700 or 800, deleting is 1 to 700 or 800,
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`and a combination of both. I can't do that math on the spot, but
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`that's -- it's a myriad combination, and it's a very broad claim with no
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`disclosure of even where the inventors thought these nucleotides
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`might exist or what nucleotides they thought might be inserted or
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`deleted or where that might be.
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`JUDGE BEGLEY: Are you disputing that it was well
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`known how to delete or insert nucleotides to inactivate a protein?
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`MS. STERLING: I'm not asserting that it was well
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`known, I'm saying with regard to these proteins in particular, the only
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`thing that was known at that time was a complete gene deletion.
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`JUDGE BEGLEY: Is there something different about
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`GRX3 or GRX4 that would make it harder than other proteins in the
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`art?
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`MS. STERLING: No, but again, I think that goes to
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`enablement as to whether a person could take this teaching and use
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`known techniques to start to screen. Whether that would, you know,
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`take undue experimentation to activate a gene by inserting one or
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`more nucleotides or deleting or both. I mean, we haven't argued that,
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`and I'm not saying those techniques weren't well known. What I'm
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`saying is, the disclosure of the words, deletion, insertion, without
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`more, without a structure-function correlation, and here there is a
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`function of inactivating a gene, the case law is clear, that's not enough
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`for a written description.
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`JUDGE CRUMBLEY: Go ahead.
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`MS. STERLING: You looked like you had another
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`question, I didn't want to interrupt.
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`JUDGE CRUMBLEY: I was thinking it through, but I
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`MS. STERLING: So, based on the disclosure of just the
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`words, without more, there's no structure-function correlation, in Eli
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`Lilly and other cases indicated that this is not enough for written
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`description support. So, based on that, the '565 patent is not entitled
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`to a priority benefit date earlier than its own filing date and Flint does
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`become prior art.
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`And then in that case, as we mentioned, Patent Owner
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`has not contended that Flint teaches all the limitations of the claims.
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`So that's really all we had to say about ground 1, if you don't have any
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`other questions.
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`JUDGE CRUMBLEY: Well, before you move on.
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`MS. STERLING: Of course.
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`JUDGE CRUMBLEY: That's one -- one rationale that
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`were some others, that we didn't really reach, but since I have you
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`MS. STERLING: Okay.
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`JUDGE CRUMBLEY: I can't remember how many
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`there were, I think it might have been four and I think the last two had
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`to do with the dependent claims, what was disclosed in the dependent
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`claims, I think one of them was the genera and species of a particular
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`yeast.
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`MS. STERLING: Um-hmm.
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`argument, because it seems to say that if you don't support the added
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`limitation of a dependent claim, then your broadest claim from which
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`it depends also lacks written description support?
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`MS. STERLING: For the full scope of that claim, yes,
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`but there may be -- I mean, I'm not saying, there's case law I know
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`that says that if you disclose sufficient species, you may disclose a
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`genus, but in this case, given that the actually claimed species, you
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`know, weren't supported in the specification, I think it's --
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`JUDGE CRUMBLEY: Yeah, I guess I'm just -- do you
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`have any case you can cite me where they've said -- where any court
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`has said that the broadest independent claim is -- lacks written
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`description support if any of its dependent claims lack written
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`description support? I mean, that just seems backwards to me.
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`MS. STERLING: Well, if you think about it, think of
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`ICU Medical, or Gentry Gallery, for example, and I think this speaks
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`more to the other dependent claim, which was mitochondrially
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`localized and cytosolically localized. So, if you think of that, that
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`depending from claim 1, you know, a dependent claim, the
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`independent claim must always be broader than the dependent claim.
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`That's settled law.
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`So, if you think about claim 1, claim 1 must encompass a
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`recombinant produced yeast where the DHAD is in the mitochondria,
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`or in the cytosol, so it's either there in place A or place B, and if the
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`specification only discloses it being in place A, there is basically no
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`written description for half of that claim, and that's essentially like
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`ICU Medical, where there was the needle, which was either spiked or
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`spikeless, but only disclosure for one of those -- it was like a generic
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`claim for a needle, but the disclosures were different.
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`So, that's the case law that we think along those lines.
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`JUDGE BEGLEY: What if there was no dependent
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`claim talking about DHAD localized in the cytosol or the
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`mitochondria? I mean, basically the way I understand your argument
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`is because they've included dependent claims, they need to cover --
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`the written description support for -- the independent claim needs to
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`cover all the dependent claims, but if they hadn't included those
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`dependent claims, the written description wouldn't have been
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`required?
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`MS. STERLING: It might have been a different story --
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`without having those hypothetical claims in front of me, it might have
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`been a different story, but here the patentee chose to claim in a way
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`that indicate claim 1 is broader than what it had support for, based
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`on --
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`JUDGE CRUMBLEY: But that doesn't make sense to
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`me because now you're saying that if they went back and deleted the
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`dependent claim, then they've solved their written description problem
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`with the broader claim, which, again, I just don't logically follow that.
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`I mean, it's almost as if you're saying -- I mean, the scope of the
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`independent claim is not going to change; you agree with me there?
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`MS. STERLING: I'm sorry, I'm nodding, yes, I agree
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`with you.
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`JUDGE CRUMBLEY: Say yes or no. So, I guess it's
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`baffling to me that the argument would turn on whether a dependent
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`claim was crafted or not.
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`MS. STERLING: I would agree with you, and I, too,
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`have had a similar issue with the same case law when the Patent
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`Owner has an opportunity to later change its claims, generally this
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`case law comes up in the Federal Circuit, we're already in District
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`Court and the patentee can no longer change its claims.
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`So, there it makes more sense, the patentee is locked in,
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`but I agree with you, in a position where the patentee can go back and
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`change claims, it does seem to lose logical sense, but we're bound by
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`the case law that's out there, and that's the rationale that was followed.
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`JUDGE CRUMBLEY: Okay.
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`MS. STERLING: Okay?
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`JUDGE BEGLEY: I have a question about the last
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`theory of written description. So, I think that shares the same like
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`legal premise about the dependent claims and the independent claim
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`written description, but for that one, you've stated that the PTO has
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`already held that the provisionals don't describe DHAD localized in
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`the mitochondria.
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`MS. STERLING: That's correct.
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`JUDGE BEGLEY: So, are you affirmatively
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`representing that the DHAD -- that the provisionals don't have that
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`disclosure, or just that we've -- the office has previously held that?
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`MS. STERLING: Both. So, to put it in context, the
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`parent application is in re-examination, where the same argument was
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`made, and there the patent office, the CRU, found no disclosure for
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`the DHAD.
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`JUDGE BEGLEY: So, I guess the problem I have with
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`that is that if there's a whole section in the 209 provisional that's titled
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`Mitochondrially Localized DHAD for Isobutanol Production. So, if
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`you don't have any discussion of that and how it doesn't disclose the
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`claim language, how can we find in your favor for that theory of lack
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`of written description?
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`MS. STERLING: I'm sorry, you said the provisionals
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`have?
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`JUDGE BEGLEY: The provisionals have disclosures of
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`DHAD localized in the mitochondria, and a whole section talking
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`about DHAD localized in the mitochondria. So, if you haven't
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`addressed that in this proceeding, how can we find in your favor?
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`MS. STERLING: I guess it's hard for you to do so.
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`JUDGE BEGLEY: Okay.
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`JUDGE CRUMBLEY: Okay.
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`MS. STERLING: Okay? So, for ground 2, slide 7,
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`please. I'm sorry, slide 6.
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`Ground 2 is an obviousness ground, where claims 1 to 4,
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`6 to 8 and 11 to 19 would have been obvious in view of Anthony,
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`Puig and Ojeda. And Gevo hasn't contested that these references are
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`prior art, nor has it contested some of the teachings in these
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`references, that Anthony teaches recombinant yeast overexpressing
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`DHAD and reduced activity of iron-sulfur cluster proteins. Puig
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`teaches that Aft induces expression of the iron regulon, including
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`Cth2, and the Cth2 is responsible for downregulating iron-sulfur
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`cluster genes. And this is not contested that Ojeda teaches that
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`deleting GRX3/4 decreases enzymatic activity of the iron-sulfur
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`cluster proteins.
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`What is contested, next slide, please, on slide 7, is the
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`first argument is that Anthony does not teach inactivating GRX3/4,
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`but this is a combination of prior art that renders this claim
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`warrantless.
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`The second argument is that Anthony and Puig teach
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`against overexpressed DHAD, but this argument ignores that Puig
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`teaches downregulation of endogenous DHAD, and there's a
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`difference there. And this similarly goes with Ojeda, Ojeda
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`apparently teaches away from the claims, but Ojeda, again, is related
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`to endogenous iron-sulfur proteins, not heterogeneously expressed or
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`exogenous iron-sulfur proteins like the claim requires.
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`So, if we go to the last slide, for example. If I can
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`explain, this is a figure from Flint, this is really the background
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`discussion that's presented in the petition, here's a cell, and we see, we
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`have this complex here, so there's Aft with GRX3/4 and Fra2, and it's
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`localized in the mitochondria, and depending on whether iron
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`conditions are high or low, this complex will stay in the mitochondria,
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`or in low-iron conditions, it disassociates and the Aft translates into
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`the nucleus. Aft is a transcription factor.
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`So, what activates the cell and tells the cell to make the
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`iron proteins that is needed, whether it's involved in iron-sulfur cluster
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`formation, iron uptake, scaffolding building, whatever the cell needs
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`the iron for, these genes are upregulated. And one of these is to make
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`iron-sulfur cluster proteins.
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`Certain enzymes and cells, DHAD being one of them,
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`uses iron-sulfur cluster as a cofactor, so it needs the iron-sulfur
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`clusters to work.
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`So, this was all well known in the art, and Anthony
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`teaches a pathway for making isobutanol from pyruvate that includes
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`overexpressing this DHAD enzyme, which is known to require
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`iron-sulfur cluster proteins. Anthony teaches deleting other proteins
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`in the cell that would use these iron-sulfur cluster proteins in order to
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`delete or get rid of the competition for the iron-sulfur clusters, and a
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`person of ordinary skill in the art would understand that's one way of
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`achieving more iron-sulfur clusters, as a cofactor for your DHAD, but
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`in view of the teaching of Ojeda and Puig, and there were other ways
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`available.
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`So, if we go back to the slide 11. So, this is recreating
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`basically what Puig has in words, and this is from the expert
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`declaration in the petition. Here, again, there's the iron complex that
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`we talked about in high-iron conditions, that's localized in the cytosol,
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`and then in low-iron conditions, there's disassociation and the Aft
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`translocates to the nucleus, where we start seeing these genes being
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`made, and these genes go to iron uptake, iron-sulfur cluster
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`formulation, and assembly.
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`There's also this Cth2 gene, and Ojeda shows that
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`deleting GRX3 or 4 activates Aft. The Cth2 gene, Puig identifies the
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`Cth2 gene downregulates endogenous iron-sulfur cluster proteins and
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`it does so through targeting an area in the 3' untranslated region.
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`So, in this case, overexpressing Aft, you would make
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`more iron-sulfur clusters, and get rid of the iron iron-sulfur cluster
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`proteins that are endogenously made in the cell. So, this would give
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`you like a one-two punch if you think about it, you're getting rid of
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`your competitors, and you're making more cofactor.
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`Now, the teaching away argument is that Cth2
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`downregulates native DHAD, but the art does not teach away from
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`exogenous or heterogeneously expressed or exogenous DHAD, and
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`that's because a person of ordinary skill in the art knowing of the
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`teachings and where the target is in the 3' untranslated region that
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`Cth2 targets has a reason to use a promoter, which does not have these
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`targets in it, and those promoters were well known in the art, there's a
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`textbook cited Sambrook in the record that gives a lot of promoters
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`that do not have these targets that the Cth would essentially target and
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`chew up the mRNA, so these proteins aren't being made.
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`So, if you're overexpressing an exogenous mRNA,
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`you've got a reason to do it with like targets, so it would not get
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`degraded by the Cth2. So, you would have the one-two punch of
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`deleting the competitors, increasing your cofactor while not targeting
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`the overexpressed DHAD, and it's only when you think of the art in
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`context with Anthony, Puig and Ojeda, in the context of Anthony,
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`where it tells you to overexpress an exogenous DHAD that you see
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`this teaching away as irrelevant, because you have regulated the Cth2
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`regulation and indeed you've got a reason to accommodate it.
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`JUDGE CRUMBLEY: I want to ask you about
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`Sambrook, because that was submitted with your reply brief.
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`MS. STERLING: Um-hmm.
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`JUDGE CRUMBLEY: And isn't the teaching of
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`Sambrook necessary for your prima facie case because it's making that
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`step that your expert discussed in his declaration, but to actually
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`provide some support for that, where your expert in his declaration
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`just said it as his say-so. I guess I worry that we're allowing you to
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`make your prima facie case as part of your reply brief.
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`MS. STERLING: Well, we would submit that Sambrook
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`was not required, as you know, Dr. Thiele's testimony was unrebutted
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`by another expert, it was merely rebutted by attorney argument, and it
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`was attorney argument that said, well, a person wouldn't have known
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`that these, you know, you may have these 3' untranslated regions that
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`don't have this target for Cth2, but you may not, and a person of
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`ordinary skill in the art may not have known that, and Dr. Thiele cites
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`nothing. Dr. Thiele is a person of ordinary skill in the art and brought
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`his knowledge to -- of well-known promoters to the documents that he
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`was reading.
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`So, when things are well known, like promoters that don't
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`have, you know, there's a wealth of promoters well known in the art,
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`that's the sort of thing that a POSA can bring, their own knowledge,
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`you can't ignore the knowledge that a POSA brings to reading the art.
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`So, we cited Sambrook, not that we felt we needed to to
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`support our prima facie case, but more to refute the attorney argument
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`that Dr. Thiele, you know, maybe wasn't an expert or this wasn't well
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`known in the art.
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`JUDGE CRUMBLEY: Well, I guess my concern is that,
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`you know, the statute says that these IPRs have to be based on patents
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`and printed publications. So, we can't just let an expert come in and
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`say this was obvious and tell us to basically create the prima facie
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`case on his own testimony.
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`MS. STERLING: Um-hmm.
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`JUDGE CRUMBLEY: But I also know that experts are
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`allowed to fill in gaps, and so part of my worry about this case is
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`where do we draw that line?
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`MS. STERLING: Um-hmm.
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`JUDGE CRUMBLEY: And do we allow your expert to
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`testify to this, and, I mean, I know it's not a claim element, and yet it's
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`also very -- it's a test to the sort of logical step of combining and
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`modifying all of these references.
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`MS. STERLING: Um-hmm.
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`JUDGE CRUMBLEY: And, so, I mean, if you could just
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`address -- I mean, I -- dissuade me of my concern, if you can.
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`MS. STERLING: Yeah, I mean, I think if you think of
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`Sambrook, it's a standard treatise, you know, the basic material that
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`everyone gets in their first year of undergrad. So, I guess to take your
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`argument to sort of a logical extension, it would mean that a person of
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`ordinary skill in the art couldn't maybe generally discuss PCR an
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