Case 1:22-cv-00311-WCB Document 346 Filed 02/02/24 Page 1 of 22 PageID #: 22709
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`IMPOSSIBLE FOODS INC.,
`
`Plaintiff,
`
`Civil Action No. 22-311-WCB
`
`v.
`
`MOTIF FOODWORKS, INC., and
`GINKGO BIOWORKS, INC.,
`
`Defendants.
`
`JURY TRIAL DEMANDED
`
`DEFENDANT GINKGO BIOWORKS, INC.’S
`REPLY CLAIM CONSTRUCTION BRIEF
`
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`Case 1:22-cv-00311-WCB Document 346 Filed 02/02/24 Page 2 of 22 PageID #: 22710
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`TABLE OF CONTENTS
`
`2.
`
`B.
`C.
`D.
`
`Page
`INTRODUCTION ............................................................................................................. 1
`TERMS FOR CONSTRUCTION ..................................................................................... 1
`A.
`Term 1 - “promoter element” ................................................................................. 1
`1.
`Impossible’s Brief Confirms that the Scope of “Promoter Element”
`Varies and Is Not Reasonably Certain ....................................................... 1
`Alternatively, “Promoter Element” Is a Means-Plus-Function Term
`Without Sufficient Structure Described in the Specification ..................... 5
`Term 2a – “a Mxr1 transcriptional activator sequence” ........................................ 7
`Term 3 - “[x] from P. pastoris” / “[x] from Pichia pastoris” .............................. 10
`Term 4 - “wherein the recombinant nucleic acid molecule comprises [x],
`wherein the recombinant nucleic acid molecule comprises [y]” ......................... 12
`Term 5 - “a nucleic acid molecule encoding [x] and [y]” .................................... 13
`Term 6 - “sequence to which [the /a] Mxr1 transcriptional activator binds” ...... 13
`Term 7 - “wherein each nucleic acid is operably linked to a methanol-
`inducible promoter element”................................................................................ 14
`Term 8 - “wherein the [methanol-inducible] promoter element” / “wherein
`the [at least one] methanol-inducible promoter element” .................................... 16
`CONCLUSION ................................................................................................................ 16
`
`E.
`F.
`G.
`
`H.
`
`I.
`II.
`
`III.
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`TABLE OF AUTHORITIES
`
`
`
`Page(s)
`
`Cases
`
`Baldwin Graphic Sys., Inc. v. Siebert, Inc.,
`512 F.3d 1338 (Fed. Cir. 2008)..........................................................................................15, 16
`
`Bicon, Inc. v. Straumann Co.,
`441 F.3d 945 (Fed. Cir. 2006)..................................................................................................11
`
`Erfindergemeinshaft UroPep Gbr v. Eli Lilly & Co.,
`No. 2:15-cv-1202-WCB, 2016 WL 6138124 (E.D. Tex. Oct. 21, 2016) ..........................6, 8, 9
`
`Insituform Techs., Inc. v. Cat Contracting, Inc.,
`99 F.3d 1098 (Fed. Cir. 1996)..................................................................................................15
`
`Nautilus, Inc. v. Biosig Instrs., Inc.,
`572 U.S. 898 (2014) .............................................................................................................5, 14
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc)..............................................................................2, 9
`
`Tronzo v. Biomet, Inc.,
`156 F.3d 1154 (Fed. Cir. 1998)..............................................................................................3, 4
`
`Trustees in Bankr. of N. Am. Rubber Thread Co. v. United States,
`593 F.3d 1346 (Fed. Cir. 2010)..........................................................................................12, 15
`
`Volterra Semiconductor LLC v. Monolithic Power Sys., Inc.,
`No. 19-2240-CFC-SRF (D. Del. Nov. 12, 2021) .....................................................................10
`
`Williamson v. Citrix Online, LLC,
`792 F.3d 1339 (Fed. Cir. 2015)..............................................................................................5, 6
`
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`TABLE OF ABBREVIATIONS
`
`Abbreviation
`
`Document
`
`Docket Identifier
`
`D.I. 333
`
`D.I. 338
`
`D.I. 340
`
`’656 patent
`
`’492 patent
`
`’327 patent
`
`Alper I
`
`Alper II
`
`Alper III
`
`Batt
`
`Batt II
`
`Ex. 9
`
`Defendant Ginkgo’s Opening Claim Construction
`Brief
`
`Plaintiff Impossible Food Inc.’s Answering Claim
`Construction Brief
`
`Defendant Motif Foodworks, Inc.’s Answering
`Claim Construction Brief
`
`U.S. Patent No. 10,689,656 (patent-in-suit)
`
`U.S. Patent No. 10,273,492 (patent-in-suit)
`
`D.I. 333
`
`D.I. 338
`
`D.I. 340
`
`D.I. 333-1
`
`D.I. 333-2
`
`U.S. Patent No. 9,938,327 (not patent-in-suit)
`
`D.I. 333-5
`
`Declaration of Hal Alper in Support of Impossible’s
`Opening Claim Construction Brief (previous
`briefing)
`
`D.I. 107
`
`Reply Declaration of Hal Alper in Support of
`Impossible’s Reply Claim Construction Brief
`(previous briefing)
`
`D.I. 144
`
`Declaration of Hal Alper in Support of Impossible’s
`Answering Claim Construction Brief
`
`D.I. 339
`
`Declaration of Carl Batt in Support of Ginkgo’s
`Opening Claim Construction Brief
`
`D.I. 334
`
`Declaration of Carl Batt in Support of Ginkgo’s
`Reply Claim Construction Brief
`
`Filed immediately
`after this document
`
`WO Int’l Pat. Appl. Publ. WO 2016/183163
`(PCT/US 2016/031797)
`
`Filed with this
`document
`
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`
`Abbreviation
`
`Document
`
`Docket Identifier
`
`Kranthi
`
`Li
`
`B. Kranthi et al., Identification of Mxxr1p-binding
`sites in the promoters of genes encoding
`dihydroxyacetone synthase and peroxin 8 of the
`methylotrophic yeast Pichia pastoris, 27 Yeast 705-
`711 (Mar. 2, 2010)
`
`D.I. 334-44, Ex. B-
`7, at ECF pages 30-
`36
`
`P. Li et al., Expression of Recombinant Proteins in
`Pichia Pastoris, 142 Appl. Biochem. Biotechnol.
`105-124 (2007)
`
`D.I. 339-1, Ex. 3 at
`ECF pages 26-46
`
`Redden & Alper
`
`H. Redden & H. Alper, The development and
`characterization of synthetic minimal yeast
`promoters, 6:7 Nature Commc’ns 810 (July 17,
`2015)
`
`Suppmann
`
`U.S. Patent No. 7,118,901 to Suppmann
`
`U.S. Pat. Appl. No.
`2023/0257793
`
`U.S. Patent No.
`11,702,665
`
`U.S. Patent Application No. 2023/0257793
`
`U.S. Patent No. 11,702,665 to Curtis
`
`WO 2015/148680
`
`WO Int’l Pat. Appl. Publ. WO 2015/148680
`
`D.I. 339-1, Ex. 2 at
`ECF pages 16-25
`
`D.I. 339-1, Ex. 4 at
`ECF pages 47-77
`
`D.I. 339-2, Ex. 8 at
`ECF pages 63-357
`
`D.I. 339-1, Ex. 6 at
`ECF pages 173-236
`
`D.I. 339-2, Ex. 7 at
`ECF pages 1-62
`
`Yeast Patents
`
`U.S. Patent No. 10,689,656 and U.S. Patent No.
`10,273,492 (the patents-in-suit)
`
`D.I. 333-1 & D.I.
`333-2
`
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`I.
`
`INTRODUCTION
`
`Impossible’s responsive brief confirms that its proposed constructions are untethered to
`
`the intrinsic record and, in many instances, contrary to what Impossible previously told this
`
`Court or the PTAB. Ginkgo’s constructions are supported by the intrinsic and extrinsic evidence
`
`and should be adopted.
`
`II.
`
`TERMS FOR CONSTRUCTION
`
`A.
`
`Term 1 - “promoter element”
`
`1.
`
`Impossible’s Brief Confirms that the Scope of “Promoter Element”
`Varies and Is Not Reasonably Certain
`
`Impossible’s own prior assertions about the term “promoter element” demonstrate that
`
`the term is indefinite, because even Impossible cannot figure out what it means.
`
`
`
`Initially, Impossible provided no definition, vaguely asserting the term has a “plain
`
`and ordinary meaning.” D.I. 94-1 at 10; D.I. 314-1 at 1.
`
` Next, when this Court asked Impossible to elucidate the plain and ordinary meaning,
`
`Impossible contended that “promoter element” was “something” that “modulates,
`
`directs or regulates expression.” D.I. 333-3 at 10:13-19.
`
` Now, Impossible contends that the plain and ordinary meaning is “a polynucleotide
`
`that regulates (e.g., drives) transcription of a polynucleotide sequence (e.g., gene)”
`
`and “is upstream of, and adjacent to or in close physical proximity to the gene.” D.I.
`
`338 at 1.
`
`This third time is not the charm. Impossible’s answering brief never once explains why its new
`
`proposal is correct in light of the intrinsic record. See Batt II ¶¶ 6-7, 12-18. Indeed, the
`
`“promoter element” portion of Impossible’s brief is devoid of even a single cite to the
`
`specification or file history.
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`Instead, Impossible contends that a POSA would understand the meaning of “promoter
`
`element” based on “literature in the field and Ginkgo’s own patent applications.” D.I. 338 at 2.
`
`Putting aside that this is all extrinsic evidence and much of it comes long after the priority date—
`
`see Phillips v. AWH Corp., 415 F.3d 1303, 1317 (Fed. Cir. 2005) (en banc) (extrinsic evidence is
`
`“less significant than the intrinsic record in determining the legally operative meaning of the
`
`claim language”)—this reliance on literature does not help Impossible. If anything, the extrinsic
`
`evidence cited by Impossible confirms the indefiniteness of “promoter element” because it fails
`
`to define the scope of the term with reasonable certainty. See Batt II ¶¶ 19-30.
`
` For example, the Suppmann reference states that a promoter element “stimulates
`
`transcription” but is a “sub-fragment of a larger promoter sequence.” Suppmann at 2:65-2:67;
`
`Batt II ¶ 22. Redden & Alper and Li, on the other hand, use the term “promoter element” to refer
`
`to complete promoters. Redden & Alper at 2; Li at 106; see Batt II ¶¶ 20-21. U.S. Patent No.
`
`11,702,665 (which has a priority date after the Yeast Patents) uses “promoter element” and
`
`“promoter” interchangeably. Batt II ¶ 24. WO 2015/148680, at [0060]-[0061], provides the
`
`same express definition for “promoter,” “promoter element,” and “promoter sequence,” but then
`
`states that “Bacterial promoters typically include a core promoter element and additional
`
`promoter elements.” Batt II ¶ 25. The lack of any uniformity in the way these references treat
`
`“promoter element” undermines Impossible’s assertion that the term has a reasonably certain
`
`scope.
`
`Impossible also cites to a claim of the ’327 patent as support for its assertion that
`
`“promoter elements are discrete sequences found in larger promoter sequences.” D.I. 338 at 4.
`
`But Impossible concedes the ’327 patent discloses that SEQ ID NO:7 is the sequence for the
`
`complete AOX1 promoter and the claim refers to “the AOX1 promoter element” having this
`
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`sequence. D.I. 338 at 4. Thus, if anything, this claim of the ’327 patent suggests “promoter
`
`elements” and “promoters” are the same thing, but that is at odds with the specification of the
`
`Yeast Patents and Impossible’s own words. The later-added claim 11 of the ’327 patent1 cannot
`
`override the repeated, express statements in the specification that make clear that a “promoter
`
`element” is not the same as a “promoter.” See D.I. 333 at 2-3; cf. Tronzo v. Biomet, Inc., 156
`
`F.3d 1154, 1159 (Fed. Cir. 1998) (finding later-added claim invalid for lack of written
`
`description where specification defined term inconsistent with scope of later-added claim).
`
`The indefiniteness problem with “promoter element” is that the specification and file
`
`history provide the POSA with no guidance on the scope of the term beyond the fact that it is a
`
`portion of, but not the same thing as, a complete promoter. Impossible’s varying constructions
`
`only add to the uncertainty.
`
`Impossible’s expert similarly fails to commit to any meaningful definition, based on his
`
`view that “the claims do not require the promoter element direct or regulate transcription in the
`
`same fashion regardless of context. The claims simply require operably linking a promoter
`
`element to a nucleic acid such that it may drive transcription.” Alper III ¶ 372; see Batt II ¶¶ 8-
`
`11. Dr. Alper also opines that the “patent provides multiple working examples of promoter
`
`elements that drive transcription of genes.” Id. ¶ 33. But the two examples he points to only
`
`discuss the use of complete promoters. Batt II ¶ 17. While distinguishing between a “promoter”
`
`and a “promoter element therefrom,” he specifically says nothing about what the latter actually
`
`is. Batt ¶¶ 65-74.
`
`Ginkgo’s U.S. Patent Application No. 2023/0257793, relied on by Dr. Alper, further
`
`1 See Ex. 9 at claims (PCT application to which the ’327 claims priority not including what
`became claim 11).
`2 All emphases added unless noted.
`
`3
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`highlights the problem. This application, filed several years after the Yeast Patents, is cited by
`
`Impossible for the proposition that a “POSA would have understood the meaning of promoter
`
`element.” Alper III ¶ 32. But the application never uses “promoter element” as a term in
`
`isolation. Impossible’s expert instead points to a “core promoter element” and an “upstream
`
`activating sequence,” Alper III ¶ 32, both of which are described as parts of the promoter, and
`
`both of which are involved in the regulation of transcription. See, e.g., U.S. Pat. Appl. Publ. No.
`
`2023/0257793 at [0026]-[0027]; Batt II ¶¶ 26-27. Indeed, the detailed description of the “core
`
`promoter element” suggests that “promoter element” on its own is not sufficiently descriptive.
`
`The generality of Dr. Alper’s opinion concerning “promoter element” provides no
`
`specific guidance to the POSA. For example, how close is “in close proximity” to a gene? How,
`
`and in what context, must a sequence drive transcription? Dr. Alper identifies nothing in the
`
`specification that answers these questions.
`
`Indeed, Dr. Alper’s own work, cited in his declaration, effectually undermines his own
`
`opinions. In a post-priority date paper, Dr. Alper reports on his efforts to identify “minimal core
`
`promoter elements” of known promoters from millions of candidate sequences. See Redden &
`
`Alper at 2-4. Dr. Alper did not rely on physical positioning to characterize these sequences, but
`
`instead performed a “series of rigorous tests” to “identify robust minimal core elements that can
`
`be linked with minimal upstream activating sequences[.]” Id. at 2. Ultimately, Dr. Alper
`
`identified only “nine robust, minimal core elements with truly modular and context-independent
`
`function” among those millions after extensive experimentation. Id. And these nine sequences
`
`were “highly unique both among each other and to any native genomic sequences” in the
`
`organism Dr. Alper studied. Id. Are those nine, then, the “promoter elements”? Or are the
`
`“promoter elements” the original millions of candidates? Or are they something in between –
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`e.g., sequences with some context-dependent function but which are not “truly modular and
`
`context-independent”? This paper provides no reasonable certainty to a POSA, nor does it
`
`provide additional illumination to the Yeast Patents’ specification.
`
`The vagueness and uncertainty surrounding “promoter element” creates an “innovation-
`
`discouraging zone of uncertainty.” See Nautilus, Inc. v. Biosig Instrs., Inc., 572 U.S. 898, 899
`
`(2014). As Nautilus cautions, “absent a meaningful definiteness check… patent applicants face
`
`powerful incentives to inject ambiguity into their claims…. Eliminating that temptation is in
`
`order, and the patent drafter is in the best position to resolve ambiguity in patent claims.” Id. at
`
`910. That is exactly what the patent drafter failed to do here: resolve the ambiguity among many
`
`possible interpretations of what a “promoter element” might be. The term is indefinite.
`
`2.
`
`Alternatively, “Promoter Element” Is a Means-Plus-Function Term
`Without Sufficient Structure Described in the Specification
`
`Impossible does not dispute that the construction it offers for “promoter element” is
`
`functional, but it asserts that the claimed function is in “in addition to a structure.” See D.I. 338
`
`at 4 (citing D.I. 142 at 15-16). But the only structure Impossible identifies is a generic
`
`“sequence,” which provides no more guidance as to structure than the term “element.” Indeed,
`
`Dr. Alper himself asserts that a “POSA would not consider a ‘promoter element’ to comprise a
`
`random assortment of nucleotides.” Alper III ¶ 36. As Impossible itself admits in its brief “a
`
`promoter element is a functional part of a promoter—not just any sequence.…” D.I. 338 at 2
`
`(emphasis original). The en banc Federal Circuit has ruled that § 112(f) “will apply” if “the
`
`claim term fails to recite sufficiently definite structure or else recites function without reciting
`
`sufficiently definite structure for performing that function.” Williamson v. Citrix Online, LLC,
`
`792 F.3d 1339, 1351 (Fed. Cir. 2015). “Promoter element” meets this test.
`
`Impossible’s attempts to distinguish Williamson are unavailing. In that case, the Federal
`
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`Circuit explicitly called out the term “element” as among terms that “reflect nothing more than
`
`verbal constructs” that may be “tantamount to using the word ‘means’” because they typically do
`
`not connote sufficiently definite structure.” Williamson, 792 F.3d at 1350. Impossible contends
`
`that Williamson is inapplicable because it dealt with computer technology, not recombinant
`
`DNA, but the Federal Circuit did not limit the decision in that way. The problem in Williamson
`
`was that the claim element was defined by its function. That is precisely the problem here.
`
`Erfindergemeinshaft UroPep Gbr v. Eli Lilly & Co., No. 2:15-cv-1202-WCB, 2016 WL
`
`6138124, at *9 (E.D. Tex. Oct. 21, 2016) is not to the contrary. In Erfindergemeinshaft, the
`
`court considered whether a method claim was a “step-plus-function” claim governed by § 112(f).
`
`2016 WL 6138124, at *4-11. The court concluded it was not, including because the record
`
`evidence showed that the POSA knew the fundamental structural information regarding the
`
`claimed “PDE V inhibitors,” of which hundreds had been identified. Id. at *10. As a result, the
`
`court concluded the POSA “would have had a reasonably certain understanding of the structural
`
`features necessary for a particular compound to be an inhibitor of PDE V[.]” Id. at *11.
`
`In contrast here, Dr. Alper’s own work confirms that even though the POSA would
`
`understand that a “promoter element” is a sequence, the POSA would not have had a reasonably
`
`certain understanding of which structural features causes a particular sequence to be a promoter
`
`element. Batt II ¶¶ 31-33. As discussed above, Dr. Alper’s own post-priority-date work
`
`isolating core elements from among millions of putative candidates, and identifying diverse and
`
`unpredictable sequences only after extensive testing, demonstrates that there were not known,
`
`common structural features for “promoter elements” at the time of the invention. Id. Thus,
`
`unlike in Erfindergemeinshaft, a POSA would not have a reasonably certain understanding of the
`
`structural features necessary for a particular sequence to be considered a “promoter element.”
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`If § 112(f) applies, Impossible does not meaningfully dispute that the specification does
`
`not identify any structures corresponding to “promoter elements.” See Batt II ¶¶ 12-18; see also
`
`Batt ¶¶ 75-78. The term “promoter element” should thus be found indefinite under § 112(f). See
`
`D.I. 338 at 1-6; Alper III ¶¶ 23-38.
`
`B.
`
`Term 2a – “a Mxr1 transcriptional activator sequence”
`
`Although the parties agree that Term 2b—“a methanol expression regulator 1 (Mxr1)
`
`transcriptional activator”—and Term 2c—“a Mxr1 transcriptional activator sequence”—both
`
`refer to the sequence encoding the Mxr1 protein3, Impossible argues that identical Term 2a has a
`
`different meaning. Impossible’s argument relies on a contorted claim parsing and should be
`
`rejected.
`
` The below table compares Ginkgo’s and Impossible’s proposed readings of the claim,
`
`with the different interpretations shown using an added colon, numbering, and highlighting:
`
`Ginkgo’s position
`
`Impossible’s position
`
`A methylotrophic Pichia yeast cell
`comprising:
`[1a] a nucleic acid molecule encoding[:]
`[i] a heme-containing protein operably
`linked to a promoter element from
`P. pastoris and
`[ii] a Mxr1 transcriptional activator
`sequence from P. pastoris; and […]
`
`A methylotrophic Pichia yeast cell comprising:
`[1a] a nucleic acid molecule encoding
`a heme-containing protein operably
`linked to[:]
`[A] a promoter element from
`P. pastoris and
`[B] a Mxr1 transcriptional activator
`sequence from P. pastoris; and […]
`
`As explained in Ginkgo’s previous briefing, Ginkgo’s construction is supported by the
`
`specification, the intrinsic record, and the extrinsic evidence. See D.I. 333 at 8-9; accord Batt II
`
`¶¶ 34-40.
`
`Impossible objects that under Gingko’s construction, the claimed “Mxr1 transcriptional
`
`activator sequence” would not be “operably linked to anything” and that the “entire paradigm of
`
`3 See D.I. 333 at 5 and D.I. 338 at 6.
`
`7
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`claim 1 is to link a protein-encoding sequence to a promoter element and an Mxr1 consensus
`
`sequence” which allegedly would be “erased” under Ginkgo’s construction. D.I. 338 at 8. These
`
`arguments wrongly presuppose the correctness of Impossible’s parsing and should therefore be
`
`rejected. See Batt II ¶ 40. Even under Impossible’s parsing of the claim, the arguments are
`
`without merit. The claim uses “comprising” language and simply does not specify what
`
`promoter drives the claimed “Mxr1 transcriptional activator sequence.” There is also no erasure
`
`of an Mxr1 consensus sequence, as concept that is, as explained below, also indefinite.
`
`The IPR record confirms that Ginkgo’s construction is correct. In denying institution of
`
`Motif’s petition, the PTAB ruled that “Claim element 1[a] requires the claimed yeast cell to
`
`comprise a nucleic acid molecule that encodes both ‘a heme-containing protein operably linked
`
`to a promoter element from P. pastoris’ (i.e., the ‘first nucleic acid’) as well as ‘a Mxr1
`
`transcriptional activator sequence from P. pastoris’ (i.e., the ‘second nucleic acid’).” D.I. 333-8
`
`at 8. See also id. at 13 (“claim element 1[a] further requires that the nucleic acid molecule also
`
`contain a Mxr1 transcriptional activator sequence…. Petitioner has not sufficiently shown that a
`
`POSITA … would have been motivated to incorporate the nucleic acid sequence encoding a
`
`Mxr1 transcriptional activator”).
`
`Impossible also relies heavily on dependent claim 14 to support its proposed
`
`construction. Specifically, Impossible contends that Gingko’s construction cannot be correct
`
`because dependent claim 14 would then require another nucleic acid with a promoter element
`
`operably linked to two separate sequences for Mxr1 transcriptional activator proteins. D.I. 338
`
`at 8-9. Impossible ignores Ginkgo’s previous explanation, which is supported by both intrinsic
`
`and extrinsic evidence, of how Ginkgo’s construction does not lead to any “duplicat[ion]” in
`
`claim 14. See D.I. 333 at 9; Batt ¶¶ 106-113; Batt II ¶¶ 40, 42.
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`Impossible also argues that the language in the claims of the related ’327 patent—which
`
`support Gingko’s construction (D.I. 333 at 7)—should be ignored. Impossible does not dispute
`
`that these claims have the same form as claim 1 of the ’492 patent and include a dependent claim
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`that unambiguously refers to the “Mxr1 transcriptional activator sequence” as the sequence for
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`the protein, not a binding site. Id. Instead, without any support, Impossible contends that claim
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`17 of the ’327 patent reflects a “drafting error.”
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`Impossible’s “drafting error” excuse only makes sense if “Mxr1 transcriptional activator
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`sequence” in claim 1 of the ’327 patent is assumed to mean “binding site,” the very claim
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`construction question the Court is being asked to decide for the ’492 patent. This Court has
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`already rejected this sort of circular reasoning. See D.I. 176 at 5-6 (citing FG SRC LLC v. Xilinx,
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`Inc., No. 20-601, D.I. 104 at 6 (D. Del. Feb. 7, 2022)).
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`The extrinsic evidence also supports Ginkgo’s construction. See Batt at ¶¶ 91-105.
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`While Dr. Batt bases his opinions on a close reading of the claims and specification, Dr. Alper
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`does not base his opinions on intrinsic evidence. Indeed, across three declarations discussing this
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`claim element, he does not cite to the specification even once. See id.; Alper I ¶¶ 52-56; Alper II
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`¶¶ 6-10.4 Accordingly, Dr. Alper’s opinions with respect to this term should be given no weight.
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`See Phillips, 415 F.3d at 1318 (“conclusory, unsupported assertions by experts as to the
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`definition of a claim term are not useful to a court”).
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`4 The closest Dr. Alper comes is a discussion of the construction of “operably linked,” stating
`“operably linked is used in the specification to describe the relationship of nucleic acid
`sequences that drive transcription with nucleic acid sequences that encode proteins.” D.I. 339 at
`¶ 42. However, he does not cite to any particular aspect of the specification and provides no
`explanation as to how this fact supports Impossible’s construction, other than to say, without
`explanation, that Ginkgo’s construction does not make sense. Id.
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`Case 1:22-cv-00311-WCB Document 346 Filed 02/02/24 Page 15 of 22 PageID #: 22723
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`C.
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`Term 3 - “[x] from P. pastoris” / “[x] from Pichia pastoris”
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`At the status conference with the Court, Impossible stated that the plain and ordinary
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`meaning of sequence “[x] from P. pastoris” is a “sequence that is associated with P. pastoris.”
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`D.I. 333-3 at 15:10-23. Impossible now abandons this plainly indefinite interpretation and
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`reverts to unadorned “plain and ordinary meaning.” D.I. 338 at 13-14. This is despite the
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`Court’s guidance that such a construction will not be adopted. D.I. 333-3 at 5:14-6:15. This
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`failure to engage with the claim construction process is alone reason enough to reject
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`Impossible’s position. See Volterra Semiconductor LLC v. Monolithic Power Sys., Inc., No. 19-
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`2240-CFC-SRF, at 22:22-23:7 (D. Del. Nov. 12, 2021) (filed as D.I. 314-3).
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`Rather than engaging on the merits, Impossible complains that Ginkgo fails to address its
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`prior briefing on the term “from P. pastoris.” This complaint misses the mark, because the term
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`“from P. pastoris” was not previously identified for construction. Its meaning was only
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`discussed tangentially, as part of briefing on the “transcriptional activator” term, but the term
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`“from P. pastoris” is also found elsewhere in the claims. In those arguments about the
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`“transcriptional activator” term, Impossible focused on its assertion that the claims do not require
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`the Mxr1 transcriptional activator sequence to be native to the claimed host cell. See, e.g., D.I.
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`106 at 14-15; Alper I ¶¶ 57-62. In identifying this term for construction, Ginkgo used the phrase
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`“found naturally” instead of “native” to clarify that “from P. pastoris” refers to the source of the
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`DNA sequence, not whether it is native to the host cell of the challenged claims.5
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`When Impossible finally engages with the meaning of “from P. pastoris,” it asserts that
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`the “plain and ordinary” meaning of the term would encompass even engineered sequences if
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`5 Nothing was unclear about Motif’s prior position or construction. Ginkgo modified the focus
`slightly to reduce confusion. As to “native” and “naturally from,” there is no meaningful
`difference; Ginkgo believes its proposed “naturally from” language better reflects the nature of
`the dispute with Impossible.
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`Case 1:22-cv-00311-WCB Document 346 Filed 02/02/24 Page 16 of 22 PageID #: 22724
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`they have an “origin in the P. pastoris genome.” D.I. 338 at 14. But construing “from P.
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`pastoris” to mean not only DNA sequences occurring naturally in P. pastoris but also such
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`sequences “subject to ordinary, art-known manipulations (e.g., codon optimization, mutation,
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`addition of cut sites, etc.)” would strip the term of any meaning. See Bicon, Inc. v. Straumann
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`Co., 441 F.3d 945, 951 (Fed. Cir. 2006) (rejecting construction that was “contrary to the
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`principle that claim language should not be treated as meaningless”). There is no definable
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`scope to the term “from P. pastoris” if it encompasses engineered sequences. Nothing in the
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`specification supports such an interpretation.
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`Impossible defends this absurdly broad “ordinary meaning” by noting that the “Yeast
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`Patents describe genetically engineered constructs.” D.I. 338 at 14. While that is true, the Yeast
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`Patents do not describe genetically engineered constructs as being “from P. pastoris,” although
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`such constructs may include sequences “from P. pastoris.” The specification does not describe
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`any specific sequence as being “from P. pastoris” unless it occurs naturally in P. pastoris.
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`The cited Alper declarations do not support the sweeping breadth of Impossible’s
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`proposed construction. The only paragraph of the three Alper declarations that specifically
`
`addresses this issue is paragraph 15 of Alper II, where Dr. Alper cites to Example 15 of the ’656
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`patent. See Alper II ¶ 15. This example describes adding DNA coding for six additional amino
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`acids to one end of the “wild type” (naturally occurring) Mxr1 sequence. ’656 patent at 26:3-11.
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`The example does not refer to this engineered sequence in its entirety as being “from P.
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`pastoris,” and when it is claimed in claim 7 of the ’656 patent, the construct is referred to as
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`“compris[ing] a Mxr1 sequence from Pichia pastoris,” because it includes the entire naturally
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`occurring sequence of P. pastoris Mxr1. Nothing in the specification remotely suggests that
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`engineered modifications such as “codon optimization, mutation, addition of cut sites, etc.”—
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`Case 1:22-cv-00311-WCB Document 346 Filed 02/02/24 Page 17 of 22 PageID #: 22725
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`whatever “mutation” and “etc.” might mean—are included within this claim term.
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`D.
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`Term 4 - “wherein the recombinant nucleic acid molecule comprises [x],
`wherein the recombinant nucleic acid molecule comprises [y]”
`
`In a head-snapping about-face, Impossible attempts to broaden its claims by arguing
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`precisely the opposite of what it argued when it was defending against Motif’s IPR. In the IPR
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`proceedings, Impossible contended that “[C]laim 1 requires that the same recombinant nucleic
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`acid molecule comprises both the claimed first exogenous nucleic acid and the claimed second
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`exogenous nucleic acid.” D.I. 333-6 at 23 (emphasis original). The PTAB agreed and denied
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`institution. D.I. 333-7 at 10. Impossible is therefore estopped from changing the position it
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`successfully took before the PTAB “simply because [its] interests have changed.” Trustees in
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`Bankr. of N. Am. Rubber Thread Co. v. United States, 593 F.3d 1346, 1353-54 (Fed. Cir. 2010)
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`(cleaned up).
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`Impossible’s word salad of a response does not provide any basis to avoid estoppel, let
`
`alone any basis for adopting Impossible’s alleged plain and ordinary meaning. Impossible
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`asserts that “the claim does not require, and Impossible did not argue, that the ‘recombinant
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`nucleic acid’ reside entirely on a single chromosome in the yeast genome.” D.I. 338 at 19.
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`Impossible fails to explain how a recombinant nucleic acid molecule could span multiple
`
`chromosomes, but regardless, this assertion has nothing to do with the proper construction of the
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`term at issue.
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`Impossible should be held to its prior words and estopped from changing its claim
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`construction position. Even