Trials@uspto.gov
`571.272.7822
`
`
`
`
`
` Paper No. 51
`
` Entered: September 11, 2019
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MODERNA THERAPEUTICS, INC.,
`Petitioner,
`
`v.
`
`PROTIVA BIOTHERAPEUTICS, INC.,
`Patent Owner.
`____________
`
`Case IPR2018-00739
`Patent 9,364,435 B2
`____________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`RICHARD J. SMITH, Administrative Patent Judges.
`
`MITCHELL, Administrative Patent Judge.
`
`
`
`
`
`
`
`FINAL WRITTEN DECISION
`
`Determining Claims 1–6, 9, 12, 14, and 15
`Unpatentable in Inter Partes Review
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`Determining Claims 7, 8, 10, 11, 13, and 16–20
`Not Unpatentable in Inter Partes Review
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`Denying Patent Owner’s Motion to Amend
`35 U.S.C. § 316(d) and 37 C.F.R. § 42.121
`
`
`
`
`
`571.272.7822
`
`
`
`
`
` Paper No. 51
`
` Entered: September 11, 2019
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MODERNA THERAPEUTICS, INC.,
`Petitioner,
`
`v.
`
`PROTIVA BIOTHERAPEUTICS, INC.,
`Patent Owner.
`____________
`
`Case IPR2018-00739
`Patent 9,364,435 B2
`____________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`RICHARD J. SMITH, Administrative Patent Judges.
`
`MITCHELL, Administrative Patent Judge.
`
`
`
`
`
`
`
`FINAL WRITTEN DECISION
`
`Determining Claims 1–6, 9, 12, 14, and 15
`Unpatentable in Inter Partes Review
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`Determining Claims 7, 8, 10, 11, 13, and 16–20
`Not Unpatentable in Inter Partes Review
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`Denying Patent Owner’s Motion to Amend
`35 U.S.C. § 316(d) and 37 C.F.R. § 42.121
`
`
`
`
`
`
`IPR2018-00739
`Patent 9,364,435 B2
`
`
` INTRODUCTION
`This is a final written decision in inter partes review of claims 1–20
`of U.S. Patent No. 9,364,435 B2 (Ex. 1001, “the ’435 patent”) entered
`pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. For the reasons set
`forth below, we determine that Petitioner has shown by a preponderance of
`the evidence that claims 1–6, 9, 12, 14, and 15 of the ’435 patent are
`unpatentable under 35 U.S.C. § 102. See 35 U.S.C. § 316(e). We also
`determine that Petitioner has not shown by a preponderance of the evidence
`that claims 7, 8, 10, 11, 13, or 16–20 are unpatentable.
`Because we have found only some of the challenged claims
`unpatentable, we address Patent Owner’s contingent Motion to Amend
`concerning proposed substitute claims for those unpatentable claims, which
`are proposed substitute claims 21–26, 29, 32, 34, and 35. We also find that
`Patent Owner’s proposed substitute claims 21–26, 29, 32, 34, and 35 are
`unpatentable. Therefore, we deny Patent Owner’s Motion to Amend.
`
`Procedural History
`A.
`Moderna Therapeutics, Inc. (“Petitioner”) 1 filed a Petition to institute
`an inter partes review of claims 1–20 (the “challenged claims”) of the
`’435 patent. Paper 2 (“Pet.”); see 35 U.S.C. §§ 311–319. Petitioner relied
`upon the Declaration of Andrew S. Janoff, Ph.D. to support its challenge.
`
`
`1 Petitioner states that the name of its parent has been changed to Moderna,
`Inc., and that Moderna, Inc.’s intellectual property matters are now
`conducted under the name of ModernaTX, Inc., which is a fully-owned
`subsidiary of Moderna, Inc. Paper 46, 2.
`2
`
`
`
`IPR2018-00739
`Patent 9,364,435 B2
`See generally Pet. Protiva Biotherapeutics, Inc. (“Patent Owner”)2 filed a
`Preliminary Response to the Petition. Paper 12 (“Prelim. Resp.”).
`Pursuant to 35 U.S.C. § 314(a), on September 12, 2018, we instituted
`an inter partes review of challenged claims 1–20 (Paper 15, “Inst. Dec.” or
`“Institution Decision”) instituting inter partes review of all challenged
`claims under all asserted grounds. Inst. Dec. 33. Patent Owner filed a
`Response (Paper 24, “PO Resp.”) supported by the Declaration of David H.
`Thompson, Ph.D (Ex. 2009). Petitioner filed a Reply (Paper 28, “Reply”)
`supported by a second Declaration of Dr. Janoff (Ex. 1021), and Patent
`Owner filed an authorized Sur-reply (Paper 34, “Sur-reply”). See Papers 16,
`19 (authorizing Patent Owner’s Sur-Reply).
`Patent Owner filed a contingent motion to amend (Paper 26
`(corrected), “Mot.”) supported by a Declaration of Dr. Thompson
`(Ex. 2040), which Petitioner opposed (Paper 29, “Opposition to Motion to
`Amend”) with a supporting Declaration of Dr. Janoff (Ex. 1020). Patent
`Owner filed a Reply to Petitioner’s opposition. Paper 33, “Reply Opp.”
`At the request of both parties, we held an oral hearing on June 6,
`2019, and the transcript of that hearing has been entered into the record.
`Paper 49 (“Tr.”).
`
`
`2 According to Patent Owner, Protiva Biotherapeutics, Inc. (“Protiva”)
`existed as a wholly-owned subsidiary of Arbutus Biopharma Corporation
`and was amalgamated into Arbutus Biopharma Corporation in January 2018.
`Paper 14, 2. Patent Owner identifies Arbutus Biopharma Corporation (fka
`“Tekmira”), Genevant Sciences, Ltd., and its fully owned subsidiaries:
`Genevant Sciences Holding, Ltd., Genevant Sciences Corporation, Genevant
`Sciences, Inc., and Genevant Sciences, GmbH, as the real parties in interest.
`Id.
`
`3
`
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`IPR2018-00739
`Patent 9,364,435 B2
`
`Related Proceedings
`B.
`Patent Owner identifies the following related matters:
`Moderna Therapeutics, Inc. v. Protiva Biotherapeutics, Inc.,
`IPR2018-00680 regarding U.S. Patent No. 9,404,127 B2; and European
`Patent Office Opposition proceedings regarding EP 2 279 254. Paper 14, 2.
`
`The ’435 Patent (Ex. 1001)
`C.
`The ’435 patent relates to “stable nucleic acid-lipid particles (SNALP)
`comprising a nucleic acid (such as one or more interfering RNA), methods
`of making the SNALP, and methods of delivering and/or administering the
`SNALP.” Ex. 1001, Abstract. The ’435 patent states that “[t]he present
`invention is based, in part, upon the surprising discovery that lipid particles
`comprising from about 50 mol % to about 85 mol % of a cationic lipid, from
`about 13 mol% to about 49.5 mol % of a non-cationic lipid, and from about
`0.5 mol % to about 2 mol % of a lipid conjugate provide advantages when
`used for the in vitro or in vivo delivery of an active agent, such as a
`therapeutic nucleic acid (e.g., an interfering RNA).” Id. at 5:55–62. The
`’435 patent further states that
`the present invention provides stable nucleic acid-lipid particles
`(SNALP) that advantageously impart increased activity of the
`encapsulated nucleic acid (e.g., an interfering RNA such as
`siRNA) and improved tolerability of the formulations in vivo,
`resulting in a significant increase in the therapeutic index as
`compared to nucleic acid-lipid particle compositions previously
`described. Additionally, the SNALP of the invention are stable
`in circulation, e.g., resistant to degradation by nucleases in serum
`and are substantially non-toxic to mammals such as humans.
`Id. at 5:62–6:5.
`
` The ’435 patent identifies specific SNALP formulations that
`encapsulate siRNA as the nucleic acid, such as the 1:57 SNALP and the 1:62
`
`4
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`IPR2018-00739
`Patent 9,364,435 B2
`SNALP, and states that “the Examples herein illustrate that the improved
`lipid particle formulations of the invention are highly effective in
`downregulating the mRNA and/or protein levels of target genes.” Id. at 6:5–
`30.
`
`Illustrative Claim
`D.
`Petitioner challenges claims 1–20 of the ’435 patent. Claim 1 is
`illustrative and reproduced below:
`1. A nucleic acid-lipid particle comprising:
`(a) a nucleic acid;
`(b) a cationic lipid comprising from 50 mol % to 85 mol % of the
`total lipid present in the particle;
`(c) a non-cationic lipid comprising from 13 mol % to 49.5 mol %
`of the total lipid present in the particle; and
`(d) a conjugated lipid that inhibits aggregation of particles
`comprising from 0.5 mol % to 2 mol % of the total lipid present
`in the particle.
`Ex. 1001, 89:55–63.
`
`Claim 1 is the only independent claim, and claims 2–20 are directly or
`indirectly dependent on claim 1. Id. at 89:55–92:22.
`
`The Instituted Grounds of Unpatentability
`E.
`We instituted the instant trial based on the following grounds of
`unpatentability. Inst. Dec. 5, 33.
`
`5
`
`
`
`IPR2018-00739
`Patent 9,364,435 B2
`Reference[s]
`WO 2005/007196 A23 and
`US 2006/0134189 A14
`’196 PCT, ’189 Publication,
`Lin,5 and Ahmad6
`US 2006/0240554 A17
`
`Basis
`§ 103
`
` § 103
`
`Claims challenged
`1–20
`
`1–20
`
`§§ 102 and 103 1–20
`
` ANALYSIS
`
`Person of Ordinary Skill in the Art
`A.
`Petitioner asserts that a person having ordinary skill in the art
`(“POSITA”) “would have specific experience with lipid particle formation
`and use in the context of delivering therapeutic payloads, and would have a
`Ph.D., an M.D., or a similar advanced degree in an allied field (e.g.,
`biophysics, microbiology, biochemistry) or an equivalent combination of
`education and experience.” Pet. 5 (citing Ex. 1007 ¶¶ 31–32). Petitioner
`further states that “[t]his level of skill is representative of the inventors on
`the ’435 patent and authors/inventors of prior art cited herein.” Id. at 6. We
`
`
`3 Ian MacLachlan et al., WO 2005/007196 A2, published Jan. 27, 2005
`(“’196 PCT”). Ex. 1002.
`4 Ian MacLachlan et al., US 2006/0134189 A1, published June 22, 2006
`(“’189 Publication”). Ex. 1003.
`5 Alison J. Lin et al., Three-Dimensional Imaging of Lipid Gene-Carriers:
`Membrane Charge Density Controls Universal Transfection Behavior in
`Lamellar Cationic Liposome-DNA Complexes, 84 BIOPHYSICAL J. 3307–16
`(2003) (“Lin”). Ex. 1005.
`6 Ayesha Ahmad et al., New Multivalent Cationic Lipids Reveal Bell Curve
`for Transfection Efficiency Versus Membrane Charge Density: Lipid-DNA
`Compleses for Gene Delivery, 7 J. GENE MED. 739–48 (2005) (“Ahmad”).
`Ex. 1006.
`7 Tongqian Chen et al., US 2006/0240554 A1, published Oct. 26, 2006
`(“’554 Publication”). Ex. 1004.
`
`6
`
`
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`IPR2018-00739
`Patent 9,364,435 B2
`applied that description for purposes of our Institution Decision. Inst.
`Dec. 7.
`Patent Owner objects to Petitioner’s proffered definition for two
`reasons. PO Resp. 9–10 (citing Ex. 2009 ¶¶ 22–24). First, Patent Owner
`objects to Petitioner’s equating the level of ordinary skill with the level of
`skill of the inventors of the ’435 patent. Id. According to Patent Owner,
`“the petition has improperly assumed a much higher level of skill than that
`of a person of ordinary skill in the art (“POSITA”).” Id. at 10 (citing
`Ex. 1007 ¶ 31; 2009 ¶¶ 22–24; Ex. 2028, 44:8–12). Patent Owner further
`states that “[b]ecause the petition sets the level much higher, to that of the
`inventors, Petitioner has failed to conduct an appropriate analysis.” Id. at 10
`(citing Ex. 2009 ¶¶ 23–24).
`As an initial matter, we did not rely on Petitioner’s statement that the
`proposed level of skill is representative of the inventors on the ’435 patent in
`our Institution Decision, and we do not rely on it for purposes of this
`Decision. See Inst. Dec. 6. We do not view Petitioner’s statement regarding
`the proposed level of ordinary skill as representative of the inventors on the
`’435 patent as part of Petitioner’s proposed level of ordinary skill in the art.
`Second, Patent Owner objects to Petitioner’s definition of a person of
`ordinary skill because it is indeterminable. PO Resp. 10. Patent Owner
`bases this contention on its characterization of Dr. Janoff’s testimony during
`cross-examination. Id. Patent Owner states that Dr. Janoff “repeatedly
`indicat[ed] that Petitioner’s own definition is ‘too vague’ to understand.” Id.
`(citing Ex. 2028, 33:6–14, 34:7–35:25, 36:1–37:5). Although Dr. Janoff
`may not have been as responsive to some questions during his deposition as
`may have been appropriate, see PO Resp. 4–8, what Dr. Janoff said in the
`cited portions of his testimony was that the questions from Patent Owner’s
`
`7
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`IPR2018-00739
`Patent 9,364,435 B2
`counsel were “too vague.” See Ex. 2028, 3:36–14, 34:7–35:25, 36:1–37:5.
`The cited portions of Dr. Janoff’s testimony indicate that, rather than
`specifically asking about Petitioner’s proposed definition of a person having
`ordinary skill in the art, Dr. Janoff was asked questions about his work
`experience. Id.; see, e.g., id. at 33:7–8, 35:7–8 (“Do you have specific
`experience working with lipid particles?” “Do you have any experience with
`any therapeutic payload?”).
`Although Patent Owner cites to Dr. Thompson’s testimony in support
`of its objections to Petitioner’s definition, it does not expressly proffer its
`own definition of a person of ordinary skill in the art. PO Resp. 9–10 (citing
`Ex. 2009 ¶¶ 22–24). Dr. Thompson states that “Dr. Janoff has not simply
`applied a slightly higher level of skill in the art in setting forth his opinions
`in his declaration, but has assumed a much higher level of skill than that of a
`person of ordinary skill in the art.” Ex. 2009 ¶ 24. Dr. Thompson, however,
`does not proffer what he considers to be an appropriate level of ordinary
`skill in the art. See generally Ex. 2009.
`Accordingly, we find on the record as a whole that a person of
`ordinary skill in the art would have specific experience with, and/or be
`generally familiar with, lipid particle formation and use in the context of
`delivering therapeutic payloads, and would have a Ph.D., an M.D., or a
`similar advanced degree in an allied field (e.g., biophysics, microbiology,
`biochemistry) or an equivalent combination of education and experience.
`We also find on this record that both Dr. Janoff and Dr. Thompson are ones
`of at least ordinary skill in the art under this standard. See Ex. 1007 ¶¶ 8–22;
`Ex. 1018 (curriculum vitae of Dr. Janoff); Ex. 2009 ¶¶ 1–6; Ex. 2010
`(curriculum vitae of Dr. Thompson).
`
`8
`
`
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`IPR2018-00739
`Patent 9,364,435 B2
`We further note that the prior art itself demonstrates the level of skill
`in the art at the time of the invention. See Okajima v. Bourdeau, 261 F.3d
`1350, 1355 (Fed. Cir. 2001) (explaining that specific findings regarding
`ordinary skill level are not required “where the prior art itself reflects an
`appropriate level and a need for testimony is not shown”) (quoting Litton
`Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158, 163–64 (Fed. Cir.
`1985)).
`
`Claim Construction
`B.
`For petitions filed before November 13, 2018, 8, the Board interprets
`claim terms in an unexpired patent according to the broadest reasonable
`construction in light of the specification of the patent in which they appear.
`37 C.F.R. § 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131,
`2142 (2016) (affirming applicability of broadest reasonable construction
`standard to inter partes review proceedings). “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.” Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062
`(Fed. Cir. 2016). Any special definitions for claim terms must be set forth
`with reasonable clarity, deliberateness, and precision. See In re Paulsen,
`30 F.3d 1475, 1480 (Fed. Cir. 1994). Only terms in controversy must be
`construed and only to the extent necessary to resolve the controversy.
`
`
`8 The Petition was filed March 5, 2018. Paper 2. See Changes to the Claim
`Construction Standard for Interpreting Claims in Trial Proceedings Before
`the Patent Trial and Appeal Board, 83 Fed. Reg. 51,340 (Oct. 11, 2018) (to
`be codified at 37 C.F.R. pt. 42).
`
`
`9
`
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`IPR2018-00739
`Patent 9,364,435 B2
`Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir.
`1999).
`As in our Decision on Institution, because Patent Owner substantively
`challenges the proposed construction of the term “nucleic acid-lipid particle”
`and relies on its narrower definition of the term in its arguments addressing
`the grounds asserted, we address the construction of that term, but find that
`we need not construe any other terms addressed by Petitioner for the purpose
`of reaching our institution decision. We again note, however, that Petitioner
`provides the same definition for “cationic lipid” as the express definition set
`forth in the specification of the ’435 patent, namely, “any of a number of
`lipid species that carry a net positive charge at a selected pH, such as
`physiological pH (e.g., pH of about 7.0).” Compare Pet. 24, with Ex. 1001,
`12:59–61.
`
`nucleic acid-lipid particle
`In our Decision on Institution, we expressly defined the term “nucleic
`acid-lipid particle. See Inst. Dec. 7–11. In construing this claim term when
`read in light of the Specification of the ’435 patent, we stated that it should
`not be limited to the definition of a stable nucleic acid-lipid particle or
`SNALP and that it should not be limited to in vivo use. See Inst. Dec. 9–10.
`We concluded that:
`Our preliminary construction of “nucleic acid-lipid
`particle” at this stage of the proceeding and for purposes of this
`decision is derived from the express definition of “lipid particle”
`as set forth in the ’435 patent that generally describes use of such
`a lipid particle to deliver nucleic acid as an active or therapeutic
`agent where the nucleic acid may be encapsulated in the lipid to
`protect it from enzymatic degradation. At this stage of the
`proceeding, we define “nucleic acid-lipid particle” as “a particle
`that comprises a nucleic acid and lipid, in which the nucleic acid
`
`10
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`IPR2018-00739
`Patent 9,364,435 B2
`may be encapsulated in the lipid portion of the particle.” See
`Ex. 1001, 11:14–22.
`Inst. Dec. 10–11.
`
`Patent Owner asserts that our proposed construction is too broad “at
`least to the extent [that it encompasses] lipid particles lacking any
`encapsulated nucleic acid.” PO Resp. 11. Patent Owner asserts that a
`“nucleic acid-lipid particle” when read in light of the Specification of the
`’435 patent requires that the nucleic acid be encapsulated in the lipid
`particle. Id. at 11–12. Patent Owner’s reasoning is as follows.
`
`A “nucleic acid-lipid particle” expressly includes a nucleic
`acid. According to the ’435 patent, “nucleic acids, when present
`in the lipid particles of the present invention, are resistant in
`aqueous solution to degradation with a nuclease.” EX1001,
`11:51–54. The ’435 patent describes nucleic acid encapsulation
`in the lipid particle as conferring resistance to such enzymatic
`degradation. EX1001, 11:20–22; see also EX2007, 4:15–19;
`22:40–45; 23:1–3; 23:27–29; 26:35–37. A “lipid particle” “may
`[include a nucleic acid] encapsulated in the lipid portion of the
`particle, thereby protecting it from enzymatic degradation.”
`EX1001, 11:14–22. A “nucleic acid-lipid particle,” however,
`does include a nucleic acid encapsulated in the lipid portion of
`the particle, thereby protecting it from enzymatic degradation.
`EX1001, 11:23–31, 11:51–54; see also EX2009 ¶39.
`PO Resp. 11–12 (emphasis in original).
`In short, Patent Owner asserts that we should construe “nucleic
`acid-lipid particle” as a SNALP. Id. at 12–13 (citing testimony of
`Dr. Janoff and Dr. Thompson and the Specification of the ’435
`patent). Patent Owner concludes, however, that whichever
`construction we choose as the broadest reasonable construction, “the
`petition fails to establish the unpatentability of claims 1–20.” PO
`Resp. 13.
`
`11
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`IPR2018-00739
`Patent 9,364,435 B2
`
`Petitioner responds that Patent Owner is trying inappropriately
`to import “serum stable” and “systemic use” limitations into the
`claims to limit the claims to a SNALP. See Reply 3–5.
`We find that our construction of “nucleic acid-lipid particle” is the
`broadest reasonable construction in light of the Specification of the ’435
`patent. 37 C.F.R. § 42.100(b); Cuozzo Speed Techs., 136 S. Ct. at 2142. For
`instance, the ’435 patent identifies a “stable nucleic acid-lipid particle” or
`SNALP as an example of a “nucleic acid-lipid particle,” see, e.g., Ex. 1001,
`3:38–39 (stating “nucleic acid-lipid particle (e.g., SNALP)”), 3:47–48, 3:57–
`58, 4:4–8, 4:12–13, 4:17–19, 27:43–45, and the term “nucleic acid-lipid
`particle” is broader than a SNALP.
`The Specification of the ’435 patent states that a SNALP requires the
`nucleic acid to be fully encapsulated within the lipid. See Ex. 1001, 11:23–
`30. A “lipid particle” with a nucleic acid as a therapeutic agent, i.e., a
`nucleic acid-lipid particle, however, may have the nucleic acid “encapsulated
`in the lipid, thereby protecting the agent [or nucleic acid] from enzymatic
`degradation.” Id. at 11:14–22 (defining “lipid particle”). Encapsulation, or
`more specifically, full encapsulation of the nucleic acid is not required
`according to the Specification of the ’435 patent.
`In fact, “lipid encapsulated” as defined in the Specification of the ’435
`patent “can refer to a lipid particle that provides an active agent or
`therapeutic agent, such as a nucleic acid (e.g., an interfering RNA), with full
`encapsulation, partial encapsulation, or both. In a preferred embodiment, the
`nucleic acid is fully encapsulated in the lipid particle (e.g., to form an SPLP,
`pSPLP, SNALP, or other nucleic acid-lipid particle).” Id. at 11:59–64. The
`Specification of the ’435 patent expressly states that only “[i]n some
`
`12
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`IPR2018-00739
`Patent 9,364,435 B2
`embodiments, the nucleic acid is fully encapsulated in the lipid particle.” Id.
`at 27:43–47.
`Dr. Thompson attempts to shoehorn the statement that nucleic acids,
`when in the lipid particles, “are resistant in aqueous solution to degradation
`with a nuclease,” to require a “nucleic acid-lipid particle” as required by the
`claims to be a SNALP. See PO Resp. 11–12; Ex. 2009 ¶¶ 39–45 (stating in
`paragraph 45 that “there is no meaningful distinction between a nucleic acid-
`lipid particle and a SNALP in the context of the ’435 patent”). Although we
`do not question that the ’435 patent touts SNALPs as the focus of the ’435
`patent, see Ex. 1001, Abst., the claims are not limited to SNALPs when the
`claims are read in light of the Specification of the ’435 patent.
`Accordingly, we construe “nucleic acid-lipid particle” as “a particle
`that comprises a nucleic acid and lipids, in which the nucleic acid may be
`encapsulated in the lipid portion of the particle.” See Ex. 1001, 15:52–63.9
`This is the same construction that we applied for purposes of the Institution
`Decision. Inst. Dec. 10–11.
`We determine that we need not expressly construe any undisputed
`terms. See Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co., 868
`F.3d 1013, 1017 (Fed. Cir. 2017) (“[W]e need only construe terms ‘that are
`in controversy, and only to the extent necessary to resolve the controversy’”)
`(quoting Vivid Techs., 200 F.3d at 803).
`
`
`9 We also continue to find that “nucleic acid-lipid particle” is not limited to
`in vivo use for the same reasons that we gave in our Decision on Institution.
`See Inst. Dec. 10.
`
`13
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`IPR2018-00739
`Patent 9,364,435 B2
`
`Principles of Law
`C.
`As set forth above, we instituted trial on all of Petitioner’s challenges
`to the claims of the ’435 patent on anticipation and obviousness grounds.
`Dec. 18; Pet. 7. The following principles of law guide our analysis of the
`asserted grounds.
`
`1. Anticipation
`To establish anticipation, each and every element in a claim, arranged
`as recited in the claim, must be found in a single prior art reference. Net
`MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008);
`Karsten Mfg. Corp. v. Cleveland Golf Co., 242 F.3d 1376, 1383 (Fed. Cir.
`2001). “A reference anticipates a claim if it discloses the claimed invention
`‘such that a skilled artisan could take its teachings in combination with his
`own knowledge of the particular art and be in possession of the invention.’”
`In re Graves, 69 F.3d 1147, 1152 (Fed. Cir. 1995) (internal citation and
`emphasis omitted). Moreover, “it is proper to take into account not only
`specific teachings of the reference but also the inferences which one skilled
`in the art would reasonably be expected to draw therefrom.” In re Preda,
`401 F.2d 825, 826 (CCPA 1968); see Eli Lilly & Co. v. Los Angeles
`Biomedical Res. Inst. at Harbor-UCLA Medical Ctr., 849 F.3d 1073, 1074–
`75 (Fed. Cir. 2017).
`“Inherency is not necessarily coterminous with the knowledge of
`those of ordinary skill in the art. . . . Artisans of ordinary skill may not
`recognize the inherent characteristics or functioning of the prior art.” Atlas
`Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (citing
`Titanium Metals Corp. v. Banner, 778 F.2d 775, 780, 782 (Fed. Cir. 1985).
`
`14
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`IPR2018-00739
`Patent 9,364,435 B2
`“[T]he discovery of a previously unappreciated property of a prior art
`composition, or of a scientific explanation for the prior art’s functioning,
`does not render the old composition patentably new to the discoverer.” Id.
`(citing Titanium Metals, 778 F.2d at 782). “It is also an elementary principle
`of patent law that when, as by a recitation of ranges or otherwise, a claim
`covers several compositions, the claim is ‘anticipated’ if one of them is in
`the prior art.” Titanium Metals, 778 F.2d at 782 (emphasis added).
`
`2. Obviousness
`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the claimed subject matter and the prior art are such that the subject
`matter, as a whole, would have been obvious at the time the invention was
`made to a person having ordinary skill in the art to which said subject matter
`pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007).
`The question of obviousness is resolved on the basis of underlying factual
`determinations including: (1) the scope and content of the prior art; (2) any
`differences between the claimed subject matter and the prior art; (3) the level
`of ordinary skill in the art; and (4) objective evidence of nonobviousness.
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). “Both the suggestion
`and the expectation of success must be founded in the prior art, not in the
`applicant’s disclosure.” In re Dow Chemical Co., 837 F.2d 469, 473 (Fed.
`Cir. 1988).
`In analyzing the obviousness of a combination of prior art elements, it
`can be important to identify a reason that would have prompted one of skill
`in the art “to combine . . . known elements in the fashion claimed by the
`patent at issue.” KSR, 550 U.S. at 418. A precise teaching directed to the
`specific subject matter of a challenged claim is not necessary to establish
`
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`IPR2018-00739
`Patent 9,364,435 B2
`obviousness. Id. Rather, “any need or problem known in the field of
`endeavor at the time of invention and addressed by the patent can provide a
`reason for combining the elements in the manner claimed.” Id. at 420.
`Accordingly, a party who petitions the Board for a determination of
`unpatentability based on obviousness must show that “a skilled artisan
`would have been motivated to combine the teachings of the prior art
`references to achieve the claimed invention, and that the skilled artisan
`would have had a reasonable expectation of success in doing so.”
`In re Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364, 1381 (Fed. Cir. 2016)
`(quotations and citations omitted).
`In KSR, the Supreme Court also stated that an invention may be found
`obvious if trying a course of conduct would have been obvious to a person
`having ordinary skill:
`When there is a design need or market pressure to solve a
`problem and there are a finite number of identified, predictable
`solutions, a person of ordinary skill has good reason to pursue
`the known options within his or her technical grasp. If this leads
`to the anticipated success, it is likely the product not of
`innovation but of ordinary skill and common sense. In that
`instance the fact that a combination was obvious to try might
`show that it was obvious under § 103.
`550 U.S. at 421. “KSR affirmed the logical inverse of this statement by
`stating that § 103 bars patentability unless ‘the improvement is more than
`the predictable use of prior art elements according to their established
`functions.’” In re Kubin, 561 F.3d 1351, 135960 (Fed. Cir. 2009) (citing
`KSR, 550 U.S. at 417).
`We analyze the asserted grounds of unpatentability in accordance with
`the above-stated principles. First, we address the anticipation and
`obviousness ground involving the ’554 Publication as it is dispositive of
`
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`IPR2018-00739
`Patent 9,364,435 B2
`many of the challenged claims. For the claims for which the ’554
`Publication does not either anticipate or render them obvious, we address the
`remaining grounds.
`
`Anticipation by or Obvious Over the ’554 Publication
`D.
`Petitioner asserts that claims 1–20 of the ’435 patent are unpatentable
`as anticipated by or obvious over the ’554 Publication. Pet. 51–64. With
`regard to its anticipation challenge, Petitioner points to a specific
`formulation taught in the ’554 Publication of a nucleic acid-lipid particle
`using the L054 formulation as described in Figure 16 with siRNA for
`reducing HBsAg levels. Id. at 52. Petitioner also points to a more general
`discussion in the ’554 Publication which it admits “does not disclose exactly
`the same ranges of lipid components from claim 1 of the ’435 patent
`explicitly, [but] it discloses encompassing and overlapping ranges and
`specific examples falling within the claimed ranges with sufficient
`specificity to anticipate.” Id. at 51.
`Patent Owner responds that the L054 formulation is not a nucleic
`acid-lipid particle as set forth in the claims, and the prior art ranges are not
`sufficiently specific to anticipate the challenged claims. PO Resp. 39–46.
`Patent Owner also asserts that “Petitioner does not provide any showing that
`the ’554 Publication would have taught or suggested the use of nucleic acid–
`lipid particles with high levels of cationic lipids and low levels of conjugated
`lipids.” Id. at 47.
`We have reviewed the complete record before us, including the
`parties’ explanations and supporting evidence presented during this trial.
`We determine that given the evidence on this record, Petitioner has shown
`
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`IPR2018-00739
`Patent 9,364,435 B2
`by a preponderance of the evidence that claims 1–6, 9, 12, 14, and 15 are
`anticipated by the ’554 Publication.
`
`1. ’554 Publication (Ex. 1004)
`The ’554 Publication involves lipid nanoparticles that transfect or
`deliver biologically active molecules, such as siRNA, to relevant cells and/or
`tissues in a subject to prevent, inhibit, or treat diseases, conditions, or traits
`in a cell, subject, or organism. Ex. 1004, Abst., ¶¶ 16–20. The ’554
`Publication notes that cationic lipids may be used to transport foreign
`nucleic acids into cells because such lipids “interact with nucleic acids
`through one end and lipid or membrane systems through another.” Id. ¶ 5.
`The ’554 Publication also identifies two structurally different complexes
`comprising nucleic acid and cationic lipid: a lamellar structure in which the
`nucleic acid monolayers sandwiched between cationic lipid bilayers, and an
`inverted hexagonal structure “in which nucleic acid molecules are encircled
`by cationic lipid in the formation of a hexagonal structure.” Id. ¶ 13. The
`inverted hexagonal structure exhibits greater transfection efficiency, but has
`very poor stability as compared to the lamellar complex. Id. The ’554
`Publication concludes that converting the complexes to an inverted
`hexagonal structure using a suitable helper lipid or a co-surfactant, however,
`is not suitable for delivery in biological systems. Id.
`Therefore, the ’554 Publication identifies a “need to design delivery
`agents that are serum stable, i.e. stable in circulation, that can undergo
`structural transformation, for example from lamellar phase to inverse
`hexagonal phase, under biological conditions.” Id. ¶ 14. In answer to this
`need, the ’554 Publication states that:
`The present application provides compounds,
`compositions and methods for significantly improving the
`
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`IPR2018-00739
`Patent 9,364,435 B2
`efficiency of systemic and local delivery of biologically active
`molecules. Among other things, the present application
`provides compounds, compositions and methods for making
`and using novel delivery agents that are stable in circulation and
`undergo structural changes under appropriate physiological
`conditions (e.g., pH) which increase the efficiency of delivery
`of biologically active molecules.
`Id. ¶ 15.
`The ’554 Publication describes a particular embodiment, the L054
`formulation. The ’554 Publication states:
`In one embodiment, the invention features a serum-stable
`formulated molecular composition comprising a biologically
`active molecule (e.g., a siNA molecule), a cationic lipid, a
`neutral lipid, and a PEG-conjugate, in which the cationic lipid
`is DMOBA, the neutral lipid is distearoylphosphatidylcholine
`(DSPC), and the PEG conjugate is PEG-DMG. In another
`embodiment, the composition further comprises cholesterol or a
`cholesterol derivative. This is known as formulation L053 or
`L054 (see Table IV).
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