Trials@uspto.gov
`571-272-7822
`
`
`Paper 11
` Entered: January 22, 2019
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BENSON HILL BIOSYSTEMS, INC.,
`Petitioner,
`
`v.
`
`THE BROAD INSTITUTE INC.,
`PRESIDENTS AND FELLOWS OF HARVARD COLLEGE &
`MASSACHUSETTS INSTITUTE OF TECHNOLOGY,
`Patent Owner.
`____________
`
`Case PGR2018-00072
`Patent 9,790,490 B2
`____________
`
`
`
`Before SHERIDAN K. SNEDDEN, CHRISTOPHER G. PAULRAJ, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`SAWERT, Administrative Patent Judge.
`
`
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`37 C.F.R. § 41.208
`
`
`
`571-272-7822
`
`
`Paper 11
` Entered: January 22, 2019
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BENSON HILL BIOSYSTEMS, INC.,
`Petitioner,
`
`v.
`
`THE BROAD INSTITUTE INC.,
`PRESIDENTS AND FELLOWS OF HARVARD COLLEGE &
`MASSACHUSETTS INSTITUTE OF TECHNOLOGY,
`Patent Owner.
`____________
`
`Case PGR2018-00072
`Patent 9,790,490 B2
`____________
`
`
`
`Before SHERIDAN K. SNEDDEN, CHRISTOPHER G. PAULRAJ, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`SAWERT, Administrative Patent Judge.
`
`
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`37 C.F.R. § 41.208
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`INTRODUCTION
`I.
`Benson Hill Biosystems, Inc. (“Petitioner”) filed a Petition for a post-
`grant review of all sixty claims of U.S. Patent No. 9,790,490 B2 (“the ’490
`patent,” Ex. 1001). Paper 2 (“Pet.”). The Broad Institute, Inc., President
`and Fellows of Harvard College & Massachusetts Institute of Technology
`(collectively, “Patent Owner”) filed a Preliminary Response. Paper 9
`(“Prelim. Resp.”).
`We have authority to determine whether to institute a post-grant
`review under 35 U.S.C. § 324 and 37 C.F.R. § 42.4(a). We may not institute
`a post-grant review unless “the information presented in the petition . . . if
`such information is not rebutted, would demonstrate that it is more likely
`than not that at least 1 of the claims challenged in the petition is
`unpatentable.” 35 U.S.C. § 324(a).
`Applying those standards, and upon consideration of the information
`presented in the Petition and the Preliminary Response, we determine that
`Petitioner has not demonstrated that it is more likely than not that at least
`one claim of the ’490 patent is unpatentable. Accordingly, we do not
`institute a post-grant review of any claim of the ’490 patent.
`A. Related Proceedings
`Petitioner and Patent Owner state that no related judicial matters are
`pending. Pet. 70. Both parties identify two pending patent applications,
`U.S. Patent Application No. 15/844,608 and U.S. Patent Application
`No. 15/783,770, which claim priority to the application leading to the ’490
`patent, as related matters. Id.; Paper 8, 1. Patent Owner also identifies
`
`
`
`2
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`pending international application PCT/US16/38181, which claims priority to
`the application leading to the ’490 patent, as a related matter. Paper 8, 1.
`B. The ’490 patent
`The ’490 patent relates to a CRISPR1 system for targeting a nucleic
`acid sequence of interest, comprising a Cpf1 effector protein and an
`engineered guide polynucleotide. Ex. 1001, Abstract. According to the ’490
`patent, the Cpf1 effector protein is a novel RNA-endonuclease. Id. at 25:59–
`60.
`
`The Cpf1 effector protein forms a complex with the guide
`polynucleotide, which is designed to hybridize to the target nucleic acid
`sequence. Id. at 26:15–17. Upon binding of the complex to the target
`sequence, the Cpf1 effector protein induces a “modification of the sequences
`associated with or at the target locus of interest.” Id. at 2:47–51. “In a
`preferred embodiment, the modification is the introduction of a strand
`break.” Id. at 3:8–9.
`Unlike other known CRISPR systems, the CRISPR-Cpf1 system of
`the ’490 patent system lacks a tracr sequence. Id. at 25:64–66. In this
`regard, “Applicants determined that Cpf1 effector protein complexes
`comprising only a Cpf1 effector protein and a crRNA (guide RNA
`comprising a direct repeat sequence and a guide sequence) were sufficient to
`cleave target DNA.” Id. at 5:40–43.
`
`
`1 CRISPR stands for “Clustered Regularly Interspaced Short
`Palindromic Repeats.” E.g., Ex. 1001, 1:48–49. CRISPR systems were first
`discovered in bacteria and archaea, where they play a role in adaptive
`immunity by specifically cleaving foreign nucleic acids. See, e.g., Ex. 2011.
`3
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`The ’490 patent also discloses engineered Cpf1 effector proteins that,
`by “mutation of one or more amino acid residues of the effector protein,”
`have “reduced or abolished nuclease activity compared with an effector
`protein lacking said one or more mutations.” Id. at 6:38–44. This “effector
`protein may not direct cleavage of one or other DNA or RNA strand at the
`target locus of interest.” Id. at 6:45–46.
`C. Challenged Claims
`Petitioner challenges claims 1–60 of the ’490 patent. Pet. 14–15. The
`’490 patent contains four independent claims. Ex. 1001, 547:49–549:26.
`Independent claims 1, 2, and 4 are drawn to an engineered, non-naturally
`occurring system comprising either a Cpf1 effector protein (claims 1 and 4)
`or a nucleotide sequence encoding a Cpf1 effector protein (claims 2 and 4),
`and at least one engineered guide polynucleotide (claims 1 and 4) or a
`nucleotide sequence encoding an engineered guide polynucleotide (claims 2
`and 4). Id. Independent claim 3 is similar, but drawn to an engineered, non-
`naturally occurring vector system. Id. at 548:58–549:9. Claim 1 is
`representative:
`1. An engineered, non-naturally occurring system
`comprising
`a) a Cpf1 effector protein, and
`b) at least one engineered guide polynucleotide designed
`to form a complex with the Cpf1 effector protein and
`comprising a guide sequence, wherein the guide sequence is
`designed to hybridize with a target sequence in a eukaryotic
`cell; and
`wherein the system lacks a tracr sequence, the engineered
`guide polynucleotide and Cpf1 effector protein do not naturally
`
`
`
`4
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`occur together, and a complex of the engineered guide
`polynucleotide and Cpf1 effector protein does not naturally
`occur.
`Id. at 547:49–61.
`
`
`
`D. Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1–60 on multiple
`grounds. Pet. 14–15. Petitioner presents the final two grounds—lack of
`utility and obviousness—as alternative grounds “if the Board disagrees with
`Petitioner’s proposed claim construction.” Id. at 14.
`Claims
`Statutory Basis
`1–60
`Lack of written description under 35 U.S.C. § 112(a) for a genus
`of Cpf1 effector proteins
`Lack of enablement under 35 U.S.C. § 112(a) for a genus of
`Cpf1 effector proteins
`Indefiniteness under 35 U.S.C. § 112(b) of “Cpf1 effector
`protein”
`Lack of enablement under 35 U.S.C. § 112(a) for a genus of
`systems lacking a tracr sequence
`Lack of written description under 35 U.S.C. § 112(a) for a genus
`of systems lacking a tracr sequence
`Lack of utility under 35 U.S.C. § 101
`Obviousness under 35 U.S.C. § 103 over Schunder,2 general
`knowledge in the art, and various secondary references
`
`1–60
`
`1–60
`
`1–60
`
`1–60
`
`1–60
`1–60
`
`Id. at 13–14. Petitioner also relies on the Declaration of Chase L. Beisel,
`Ph.D. (Ex. 1003). E.g., id. at 1. Patent Owner disputes that Petitioner’s
`asserted grounds render the challenged claims unpatentable. See generally
`Prelim. Resp.
`
`
`2 Eva Schunder et al., First Indication for a Functional CRISPR/Cas
`System in Francisella tularensis, 303 INT’L J. MED. MICROBIOL. 51–60
`(2013). Ex. 1004 (“Schunder”).
`
`
`
`5
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`II. ANALYSIS
`We address below whether the Petition meets the threshold showing
`for institution of a post-grant review under 35 U.S.C. § 321(a). We consider
`each ground of unpatentability in view of the understanding of a person of
`ordinary skill in the art.
`Petitioner contends that a person of ordinary skill in the art would
`have had an M.D. or a Ph.D. in biology, chemistry, engineering (e.g.,
`chemical engineering, biological engineering, biomedical engineering, or
`biochemical engineering), biophysics, or a related discipline, with a focus on
`genetic modification techniques and at least three years of experience
`working in industry and/or academia on genetic modification techniques.
`Pet. 9–10. Patent Owner offers no definition of a person of ordinary skill in
`the art in its Preliminary Response. Prelim. Resp. 12.
`For the purpose of this decision, we accept Petitioner’s proposed
`definition and also find that the prior art itself is sufficient to demonstrate the
`level of ordinary skill in the art at the time of the invention. See Okajima v.
`Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (the prior art, itself, can
`reflect appropriate level of ordinary skill in art). Further, based on the
`information presented at this stage of the proceeding, we consider
`Petitioner’s declarant—Dr. Beisel—qualified to opine about the perspective
`of an ordinary artisan at the time of the invention. See Ex. 1003 ¶¶ 5–16,
`Appendix B (curriculum vitae of Dr. Beisel).
`
`
`
`
`
`
`6
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`A. Eligibility for Post-Grant Review
`The post-grant review provisions set forth in Section 6(d) of the AIA3
`apply only to patents subject to the first-inventor-to-file provisions of the
`AIA. See AIA § 6(f)(2)(A) (“The amendments made by subsection (d) . . .
`shall apply only to patents described in section 3(n)(1).”). Patents subject to
`the first-inventor-to-file provisions are those that issue from applications
`“that contain[] or contained at any time . . . a claim to a claimed invention
`that has an effective filing date as defined in section 100(i) of title 35, United
`States Code, that is on or after” March 16, 2013. AIA § 3(n)(1). Our rules
`require that each petitioner for post-grant review certify that the challenged
`patent has an effective filing date that renders the patent available for post-
`grant review. 37 C.F.R. § 42.204(a) (“The petitioner must certify that the
`patent for which review is sought is available for post-grant review . . . .”).
`In addition, “[a] petition for a post-grant review may only be filed not later
`than the date that is 9 months after the date of the grant of the patent or of
`the issuance of a reissue patent (as the case may be).” 35 U.S.C. § 321(c);
`see also 37 C.F.R. § 42.202(a) (accord).
`Petitioner states that the ’490 patent is eligible for post-grant review
`because “the ’490 patent was filed under the AIA” and “this Petition is being
`filed within nine months of the date the patent issued.” Pet. 14. Patent
`Owner does not dispute post-grant review eligibility. See generally Prelim.
`Resp. On this record, we determine that the ’490 patent is eligible for post-
`grant review. Specifically, the application leading to the ’490 patent was
`
`
`3 Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat.
`284 (2011) (“AIA”).
`
`
`
`7
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`filed on December 18, 2015, and claims priority to several provisional
`applications filed in June, July, August, and September of 2015. Ex. 1001,
`(22), (60). All these dates fall after March 16, 2013. Also, this Petition was
`filed on July 17, 2018, which is nine months after the October 17, 2017,
`issue date of the ’490 patent. Id. at (45); Paper 4, 1.
`B. Claim Construction
`For petitions filed before November 13, 2018, claim terms are
`interpreted according to their broadest reasonable construction in light of the
`specification of the patent in which they appear. See 37 C.F.R. § 42.100(b)
`(2016) 4; Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016)
`(upholding the use of the broadest reasonable interpretation standard).
`Under that standard, we presume that a claim term carries its
`“ordinary and customary meaning,” which “is the meaning that the term
`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); see also Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062 (Fed. Cir.
`2016) (“Under a broadest reasonable interpretation, words of the claim must
`be given their plain meaning, unless such meaning is inconsistent with the
`specification and prosecution history.”). Any special definition for a claim
`
`
`4 The claim construction standard recently changed for all post-grant
`proceedings filed on or after November 13, 2018. See Changes to the Claim
`Construction Standard for Interpreting Claims in Trial Proceedings Before
`the Patent Trial and Appeal Board, 83 FED. REG. 51340 (Oct. 11, 2018).
`But, based on the filing date of the Petition in this proceeding, the applicable
`claim construction standard remains the “broadest reasonable construction,”
`as set forth in 37 C.F.R. § 42.100(b) (2016).
`
`
`
`
`8
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`term must be set forth in the specification with reasonable clarity,
`deliberateness, and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir.
`1994).
`Claim 1 recites “at least one engineered guide polynucleotide
`designed to form a complex with the Cpf1 effector protein and comprising a
`guide sequence, wherein the guide sequence is designed to hybridize with a
`target sequence in a eukaryotic cell.” Ex. 1001, 547:51–56. Petitioner
`argues that this language “requires a system in which the recited Cpf1
`protein exhibits effector protein function in a eukaryotic cell.” Pet. 11
`(citing Ex. 1003 ¶¶ 62, 67–68). To exhibit effector protein function,
`Petitioner argues, “the Cpf1 protein must form a complex with a guide
`sequence and be capable of hybridizing to a target sequence in a eukaryotic
`cell and cleaving the target sequence.” Id. at 13–14 (citing Ex. 1003 ¶ 70).
`Petitioner argues that the written description of the ’490 patent
`supports this interpretation, “by teaching that the claimed nucleic-acid
`targeting complexes are used for ‘modifying (e.g., deleting, inserting,
`translocating, inactivating, activating) a target DNA or RNA in a
`multiplicity of cell types.’” Pet. 11–12 (quoting Ex. 1001, 42:3–7; citing
`Ex. 1001, 77:45–54, 2:42–51, 2:65–3:8, 3:57–59; 4:5–11, 4:58–66, 30:30–
`35, 42:15–18, 43:55–63, 64:31–40, 65:2–5, 72:59–60, 73:23–32, 77:25–36,
`84:23–32, 156:29–44; 185:61–186:5). Petitioner acknowledges that the ’490
`patent discloses catalytically inactive Cpf1 effective proteins, but argues that
`these proteins are “certainly not the focus of the specification,” and that, in
`any event, Patent Owner expressly disavowed those non-functional
`
`
`
`9
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`embodiments during prosecution. Id. at 12–13 (citing Ex. 1002, 6184;
`Ex. 1003 ¶ 69).
`Petitioner also argues that “the Examiner required Patent Owners to
`amend the claims prior to allowance to recite that ‘the system lacks a tracr
`sequence,’ because this ‘was a substantive and non-obvious functional and
`structural difference from a system that required a tracr sequence’ to
`function.” Id. at 13 (quoting Ex. 1002, 7664). According to Petitioner,
`“Patent Owners’ acquiescence to this amendment, along with their other
`statements made during prosecution to overcome the prior art constitute a
`clear disavowal of claim scope and limit the claims to those systems that
`actually function to cleave a target sequence in a eukaryotic cell.” Id. at 13.
`Alternatively, Petitioner argues that “[i]f . . . the Board were to
`determine that the issued claims do not require any functional aspects, then
`Petitioner includes additional grounds of unpatentability based on lack of
`practical utility under 35 U.S.C. § 101 (Ground 6) and obviousness over
`Schunder (Ground 7).” Id. at 14.
`In response, Patent Owner argues that each of Petitioner’s “two
`alternative constructions” “is flawed because each directly conflicts with the
`plain claim language, specification, and prosecution history.” Prelim. Resp.
`12. Patent Owner argues that Petitioner’s “first proposed construction
`blatantly reads a limitation into the claims,” id. at 12, and that it and
`Petitioner’s alternative construction “should be rejected as a matter of law,”
`id. at 13. Patent Owner argues that, “[i]nstead, the claims should be given
`their plain and ordinary meaning as reflected in the words of the independent
`
`
`
`10
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`claims themselves—‘designed to hybridize with a target sequence in a
`eukaryotic cell.’” Id.
`We agree with Patent Owner. Claim 1 recites an “engineered, non-
`naturally occurring system comprising” “a Cpf1 effector protein” and “at
`least one engineered guide polynucleotide.” Ex. 1001, 547:49–61. The crux
`of Petitioner’s argument is that the claims should be limited to systems in
`which the Cpf1 effector protein is designed to cause cleavage of the target
`sequence. Pet. 11–14. Although claim 1 describes the engineered guide
`polynucleotide and guide sequence in terms of their intended functions (i.e.,
`the engineered guide polynucleotide is “designed to form a complex with the
`Cpf1 effector protein,” and the guide sequence “is designed to hybridize
`with a target sequence in a eukaryotic cell”), claim 1 does not similarly
`specify that the Cpf1 effector protein must be designed to cleave the target
`sequence. Thus, the plain language of claim 1 does not support Petitioner’s
`argument. See, e.g., Veritas Techs. LLC v. Veeam Software Corp., 835 F.3d
`1406, 1411 (Fed. Cir. 2016) (claim construction begins with the plain
`language of the claims).
`Moreover, Petitioner does not persuasively point us to any language in
`the claims themselves that would restrict the scope of the claims to only
`Cpf1 effector proteins designed to cause cleavage of the target sequence.
`For example, the written description of the ’490 patent refers to both
`catalytically active Cpf1 proteins (i.e., proteins that cleave nucleic acids) and
`catalytically inactive Cpf1 proteins (i.e., proteins that cannot cleave nucleic
`acids) as Cpf1 “effector proteins.” Compare, e.g., Ex. 1001, 3:57–59 (“The
`invention provides methods of genome editing . . . compris[ing] two or more
`
`
`
`11
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`rounds of Cpf1 effector protein targeting and cleavage.” (emphases added)),
`with id. at 6:35–48 (“The invention also provides for methods and
`compositions wherein one or more amino acid residues of the effector
`protein may be modified, e.g[.], an engineered or non-naturally-occurring
`effector protein or Cpf1. . . . The effector protein may not direct cleavage of
`one or other DNA or RNA strand at the target locus of interest.” (emphasis
`added)). Thus, the term Cpf1 “effector protein,” as recited in the claims,
`does not compel us to interpret the claims as requiring a cleavage function
`for that protein.
`Turning to the written description, the ’490 patent describes the Cpf1
`effector protein as having the function of inducing a “modification of the
`sequences associated with or at the target locus of interest.” Ex. 1001, 2:47–
`51 (emphasis added). But, contrary to Petitioner’s arguments otherwise, that
`“modification” is not limited to nucleic acid “cleavage.” For example, the
`’490 patent discloses several Cpf1 effector protein functions that do not
`include cleavage, such as: “methylase activity, demethylase activity,
`transcription activation activity, transcription repression activity,
`transcription release factor activity, histone modification activity,” and
`“nucleic acid binding activity.” Id. at 7:25–33. And the ’490 patent
`discloses several uses for the CRISPR-Cpf1 system other than for gene
`editing that requires nucleic acid cleavage—e.g., for fusion or operable
`linkage to a functional domain, id. at 37:14–22; for delivery of functional
`domains, id. at 59:9–23; for RNA-guided protein binding “with little or no
`target cleavage,” id. at 59:43–62; for “inducing transcriptional activation or
`repression,” id. at 80:51–64; for producing an “inducible Cpf1 CRISPR-Cas
`
`
`
`12
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`system,” id. at 90:47–58; for detection methods such as fluorescence in situ
`hybridization (FISH), id. at 156:45–67; and for identifying locations of
`target sequences via a tagged CRISPR enzyme, id. at 172:9–48. Petitioner
`appears to rely on the notion that these activities are “not the not the focus of
`the specification.” Pet. 12. Even if true, Petitioner has not pointed us to any
`principle of law that would allow us to read these multiple embodiments out
`of the scope of the claims. Indeed, we note that the ’490 patent describes
`nucleic acid cleavage as “a preferred embodiment.” Id. at 3:8–9;
`WesternGeco LLC v. ION Geophysical Corp., 889 F.3d 1308, 1323–24 (Fed.
`Cir. 2018) (“It is well established that claims are not limited to preferred
`embodiments, unless the specification clearly indicates otherwise.”).
`In addition, the ’490 patent specifically discloses engineered Cpf1
`effector proteins that, by “mutation of one or more amino acid residues of
`the effector protein,” have “reduced or abolished nuclease activity compared
`with an effector protein lacking said one or more mutations.” Id. at 6:38–44.
`This “effector protein may not direct cleavage of one or other DNA or RNA
`strand at the target locus of interest.” Id. at 6:45–46. The written
`description also identifies these engineered Cpf1 effector proteins as
`“preferred embodiments”: “In a preferred embodiment, the mutation in the
`FnCpf1p RuvC domain is D917A or El006A, wherein the D917A or
`E1006A mutation completely inactivates the DNA cleavage activity of the
`FnCpf1 effector protein.” Id. at 9:21–40 (emphasis added). Because a claim
`interpretation that excludes a preferred embodiment is “rarely, if ever,
`correct,” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1583 (Fed.
`
`
`
`13
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`Cir. 1996), the written description of the ’490 patent also does not support
`Petitioner’s claim construction.
`We turn next to the prosecution history of the application leading to
`the ’490 patent. See WesternGeco, 889 F.3d at 1323 (“A patent’s
`specification, together with its prosecution history, constitutes intrinsic
`evidence to which the Board gives priority when it construes claims.”).
`Disavowal of claim scope can occur when the Patent Owner makes a
`narrowing amendment to a claim or surrenders claim scope through
`argument. Conoco, Inc. v. Energy & Envt’l Int’l, L.C., 460 F.3d 1349, 1363
`(Fed. Cir. 2006). Here, Petitioner relies on both argument-based disavowal
`and amendment-based disavowal to argue that Patent Owner disavowed
`catalytically inactive Cpf1 effector proteins (i.e., proteins lacking nuclease
`activity). Pet. 12–14. We find neither persuasive.
`For argument-based disavowal to apply, the “surrender of subject
`matter” must be “clear and unmistakable.” Conoco, 460 F.3d at 1364.
`Petitioner argues that Patent Owner “expressly disclaimed non-functional
`systems” in responding to an anticipation rejection. Pet. 12–13 (citing
`Ex. 1002, 6184). During prosecution, the Examiner rejected certain claims
`for anticipation over Schunder. Ex. 1002, 6153–55. Specifically, the
`Examiner found that “Schunder discloses CRISPR-Cas systems identified in
`Francisella tularensis bacteria, which is the putative Cpf1 CRISPR-Cas
`system.” Id. at 6154. The Examiner further found that “the Francisella
`bacteria are deemed to inherently comprise the required CRISPR-Cas Cpf1
`system.” Id.
`
`
`
`14
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`In response, Patent Owner argued that Schunder failed to disclose all
`the limitations of the claims. Id. at 6184. Specifically, Patent Owner argued
`that Schunder merely “discloses no more than existence in the genome of F.
`tulerenis [sic] sequences proposed to encode putative CRISPR-Cas
`proteins,” “fails to demonstrate that any of the putative components are
`functional,” and “fails to teach or suggest elements needed to engineer an
`operable F. tulerenis [sic] CRISPR-Cas system.” Id.
`Petitioner equates “functional” and “operable” in Patent Owner’s
`prosecution remarks to both hybridization and cleavage functions, but the
`prosecution history shows that Patent Owner relied on the hybridization
`function only to distinguish the prior art. Id. First, Patent Owner
`characterized the instant claims as reciting “an engineered guide
`polynucleotide that is designed to hybridize with a target sequence.” Id.
`(second emphasis added). Second, Patent Owner argued that “Schunder
`provides no teaching or suggestion of a F. tulerenis [sic] [Protospacer
`Adjacent Motif], which would be needed to design functional guides to
`hybridize to a target of interest.” Id. (emphases added). These arguments do
`not rise to the level of a “clear and unmistakable” disavowal of CRISPR-
`Cpf1 systems comprising Cpf1 effector proteins lacking nuclease activity.
`We are similarly unpersuaded by Petitioner’s amendment-based
`disavowal argument. As Petitioner notes, the Examiner required Patent
`Owner to amend the claims before allowance to recite that the claimed
`CRISPR system lacks a tracr sequence. Pet. 13 (citing Ex. 1002, 7664). In
`an Examiner-Initiated Interview Summary, the Examiner wrote that “the
`lack of tracr sequence was a substantive and non-obvious functional and
`
`
`
`15
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`structural difference from a system that required a tracr sequence.”
`Ex. 1002, 7664. But nothing in the Examiner’s statement or amendment
`requires the Cpf1 effector protein to function to cleave a target sequence, or
`demonstrates that the Examiner understood the claims to be limited to a
`catalytically active Cpf1 effector protein. Instead, the Examiner’s Reasons
`for Allowance indicate that the Examiner relied on the ability of the
`engineered guide polynucleotide to hybridize to a target sequence in the
`absence of a tracr sequence:
`The prior art fails to disclose or suggest a system comprising a
`Cpf1 effector protein, or a sequence encoding a Cpf1 effector
`protein, and at least one engineered guide polynucleotide, which
`forms a complex with the Cpf1 effector protein. In particular, the
`prior art fails to disclose or suggest such a system that lacks a
`tracr sequence. The guide polynucleotide comprises a guide
`sequence that is designed to, and will, hybridize to a target
`sequence in a eukaryotic cell.
`Id. at 7677 (emphases added).
`For these reasons, we decline to read the claims narrowly so as to
`exclude CRISPR-Cpf1 systems comprising Cpf1 effector proteins lacking
`nuclease activity. We interpret the claims consistent with their plain
`language, the written description of the ’490 patent, and its prosecution
`history to require a system having a Cpf1 effector protein and a guide
`sequence designed to hybridize with a target sequence in a eukaryotic cell,
`but not to require cleavage of the target sequence by the Cpf1 effector
`protein. Ex. 1001, 547:54–56. No further interpretation of any claim term is
`necessary. Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803
`(Fed. Cir. 1999) (“[O]nly those terms need be construed that are in
`controversy, and only to the extent necessary to resolve the controversy.”).
`16
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`
`
`C. Proposed Grounds of Unpatentability Under 35 U.S.C. § 112
`Petitioner argues that claims 1–60 of the ’490 patent are unpatentable
`under 35 U.S.C. § 112 for lack of written description, lack of enablement,
`and indefiniteness. See Pet. 15–51. Patent Owner argues that these grounds
`of unpatentability are all “based on the Board importing a ‘cleavage’
`limitation into the independent claims.” Prelim. Resp. 23. Patent Owner
`argues that “[i]f the Board rejects Petitioner’s construction as a matter of
`law,” then we should reject these grounds of unpatentability as well. Id. We
`agree.
`“[T]he petitioner is master of its complaint.” SAS Inst. Inc. v. Iancu,
`138 S. Ct. 1348, 1355 (2018). Here, Petitioner premises its § 112 grounds of
`unpatentability on whether the written description of the ’490 patent
`adequately describes, enables, and defines Cpf1 effector proteins having
`nuclease (i.e., cleavage) activity, and makes no separate argument that the
`claims are also unpatentable if construed to not require cleavage.
`For example, Petitioner argues that the claims are unpatentable
`because the written description of the ’490 patent “fails to provide any
`correlation between the structure of the Cpf1 proteins and their claimed
`function of successfully cleaving DNA in eukaryotic cells.” Pet. 1 (emphasis
`added); see also id. at 49 (arguing that “[a]bsent positive results from a DNA
`cleavage assay, one skilled in the art would not be able to conclude whether
`any given Cpf1 protein does or does not require a tracrRNA” (emphases
`added)). Petitioner also argues that the claims lack enablement because “[i]t
`would take complex iterative testing . . . to identify the genus of Cpf1
`proteins that are functional within the meaning of the claims,” id. at 2, and
`ties that function to examples in the written description measuring nuclease
`17
`
`
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`activity in vitro and in vivo, id. at 29. See also id. at 46 (arguing that “in
`vitro cleavage assays” “are the only way to determine whether a given Cpf1
`enzyme does or does not require a tracrRNA for cleavage,” and that these
`assays are “non-trivial” (emphasis added)). Thus, in every instance,
`Petitioner ties its unpatentability analysis to the lack of adequate information
`in the ’490 patent demonstrating that a Cpf1 effector protein has nuclease
`activity. Petitioner presents no argument directing us how to analyze the
`claims when considering the full scope of the ’490 patent’s disclosure,
`which, as discussed above, includes Cpf1 effector proteins that have
`functions other than nuclease activity. See SAS Inst., 138 S. Ct. at 1358
`(“the petition [is] the centerpiece of the proceeding both before and after
`institution”).
`In coming to our conclusion, we are cognizant that rejecting
`Petitioner’s narrower interpretation of the claims in favor of Patent Owner’s
`broader interpretation results in a claim scope that encompasses both Cpf1
`effector proteins designed to be catalytically active and Cpf1 effector
`proteins that do not have catalytic activity. But Petitioner chose not to
`present any arguments that the challenged claims are unpatentable under this
`broader interpretation. We decline to parse the Petition to make these
`arguments for Petitioner. Cf. Intelligent Bio-Sys., Inc. v. Illumina
`Cambridge Ltd., 821 F.3d 1359, 1369 (Fed. Cir. 2016). Thus, Petitioner
`fails to demonstrate on this record that it is more likely than not that at least
`one claim of the ’490 patent is unpatentable for lack of written description,
`lack of enablement, or indefiniteness.
`
`
`
`
`18
`
`
`
`PGR2018-00072
`Patent 9,790,490 B2
`
`
`
`
`
`
`D. Proposed Alternative Grounds of Unpatentability
`Petitioner argues that, “if . . . the Board were to determine that the
`issued claims do not require any functional aspects,” then claims 1–60 of the
`’490 patent are unpatentable under 35 U.S.C. § 101 for lack of practical
`utility and under 35 U.S.C. § 103 for obviousness. Pet. 14; see also id. at
`51–69. Because we do not so interpret the claims, however, Petitioner fails
`to demonstrate that it is more likely than not that at least one claim of the
`’490 patent is unpatentable under these grounds.
`For example, as to the ground of unpatentability based on
`obviousness, Petitioner predicates its arguments on a determination by the
`Board that “the claims require no functional activity.” Pet. 55. But, as
`explained above, the plain language of claim 1 recites “an engineered guide
`polynucleotide . . . comprising a guide sequence . . . designed to hybridize
`with a target sequence.” Ex. 1001, 547:52–56 (emphasis added).
`Hybridization is a functional activity. And, as to the ground of
`unpatentability based on lack of practical utility, Petitioner again ties its
`arguments to a limitation we do not read into the claims—i.e., cleaving the
`target sequence. See Pet. 53 (arguing that “to be useful under § 101, the
`claimed subject matter must actually function in a eukaryotic cell to cleave
`DNA” (emphasis added)). These alternative grounds fail to address the
`utility and obviousness of other Cpf1 effector protein functions disclosed in
`the ’490 patent that do not require cleavage, such as, “methylase activity,
`demethylase
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
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.
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.
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
