Trials@uspto.gov
`Tel: 571-272-7822
`
`
`
`
`Paper No. 7
`Entered: June 20, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`INITIATIVE FOR MEDICINES, ACCESS & KNOWLEDGE (I-MAK), INC.,
`Petitioner
`v.
`GILEAD PHARMASSET LLC
`Patent Owner
`_______________
`
`Case IPR2018-00211
`Patent 9,393,256 B2
`_______________
`
`
`Before LORA M. GREEN, GRACE KARAFFA OBERMANN, and
`RICHARD J. SMITH, Administrative Patent Judges.
`
`SMITH, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
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`Case IPR2018-00211
`Patent 9,393,256 B2
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`
`INTRODUCTION
`I.
`Initiative for Medicines, Access & Knowledge (I-MAK), Inc. (“Petitioner”)
`filed a Petition (Paper 2, “Pet.”) to institute an inter partes review of claims 1–4 of
`U.S. Patent 9,393,256 B2 (the “’256 patent”). 35 U.S.C. § 311. Gilead Pharmasset
`LLC (“Patent Owner”) filed a Preliminary Response to the Petition. Paper 6
`(“Prelim. Resp.”).
`We have authority to determine whether to institute an inter partes review
`under 35 U.S.C. § 314. To institute an inter partes review, we must determine that
`the information presented in the Petition shows “a reasonable likelihood that the
`petitioner would prevail with respect to at least 1 of the claims challenged in the
`petition.” 35 U.S.C. § 314(a). For the reasons set forth below, we conclude that
`Petitioner has not established a reasonable likelihood that it would prevail in
`showing the unpatentability of any challenged claim of the ’256 patent. Therefore,
`we do not institute an inter partes review for any challenged claim of the ’256
`patent.
`
`Related Proceedings
`A.
`Petitioner has also filed two petitions for inter partes review of U.S. Patent
`No. 7,964,580 (Case Nos. IPR2018-00119 and IPR2018-00120); two petitions for
`inter partes review of U.S. Patent No. 8,334,270 (Case Nos. IPR2018-00121 and
`IPR2018-00122); one petition for inter partes review of U.S. Patent No. 7,429,572
`(Case No. IPR2018-00103); one petition for inter partes review of U.S. Patent No.
`8,633,309 (Case No. IPR2018-00125); and one petition for inter partes review of
`U.S. Patent No. 9,284,342 (Case No. IPR2018-00126). Paper 3, 2.
`The ’256 Patent
`B.
`The ’256 patent relates to compositions and therapeutic methods useful for
`treating viral infections, such as hepatitis C virus (HCV). Ex. 1001, 2:63–65. For
`
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`Patent 9,393,256 B2
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`example, the ’256 patent discloses a method of treating an HCV infection in a
`human comprising administering two or more compounds selected from a group
`that includes Compound 6 and Compound 10 (see claim 1 below). Id. at 3:11–15;
`139: l. 6–140: l. 21. The ’256 patent indicates that compound 10 is an NS5B
`nucleoside prodrug and compound 6 is an NS5A inhibitor. Id. at 133:55–61;
`134:24–35. The ’256 patent also states that the disclosed methods “are beneficial
`because they provide treatments for a wide range of HCV genotypes and . . . cause
`fewer or less serious side effects than current HCV therapies.” Id. at 4:55–58.
`Illustrative Claim
`C.
`Petitioner challenges claims 1–4 of the ’256 patent, of which claim 1 is the
`only independent claim. Claim 1 is reproduced below:
`1. A method of treating an HCV infection in a human,
`comprising administering to the human: 1) compound 10 having the
`structure:
`
`
`
`
`or a pharmaceutically acceptable salt thereof and 2) compound 6 having
`the structure:
`
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`Patent 9,393,256 B2
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`or a pharmaceutically acceptable salt thereof, wherein the method does
`not include administering interferon.
`Ex. 1001, 139: l. 6–140: l. 21.
`
`Claims 2–4 depend directly from claim 1.1 Id. at 140:22–27.
`
`
`
`The Asserted Grounds of Unpatentability
`D.
`Petitioner contends that the challenged claims are unpatentable under
`35 U.S.C. §§ 102 and 103 based on the following grounds. Pet. 3.
`
`Reference[s]
`Legrand-Abravanel2
`
`Claims challenged
`1–4
`
`Basis
`§§ 102(b) and
`103(a)
`§ 102(e)
`
`Delaney3
`
`Sofia ’6344 and Guo5
`
`§103(a)
`
`1–4
`
`1–4
`
`
`Petitioner also relies on the Declaration of Joseph M. Fortunak, Ph.D.
`Ex. 1012.
`
`
`1 For example, claim 4 recites “[t]he method of claim 1 further comprising
`administering ribavirin to the human.” Ex. 1001, 140:26–27.
`2 F. Legrand-Abravanel et al., New NS5B polymerase inhibitors for hepatitis C,
`Expert Opinion Investigational Drugs 19(8), 963–75 (2010) (“Legrand-
`Abravanel”). Ex. 1005.
`3 Delaney, IV et al., US 2011/0306541 A1, published Dec. 15, 2011 (“Delaney”).
`Ex. 1010.
`4 Sofia et al., WO 2008/121634 A2, published Oct. 9, 2008 (“Sofia ’634”). Ex.
`1004.
`5 Guo et al., WO 2010/132601 A1, published Nov. 18, 2010 (“Guo”). Ex. 1011.
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`
` ANALYSIS
`Person of Ordinary Skill in the Art
`A.
`Petitioner asserts that a person of ordinary skill in the art would have either
`“(1) a Ph.D. in chemistry or a closely related field with some experience in an
`academic or industrial laboratory focusing on drug discovery or development, and
`would also have some familiarity with antiviral drugs and their design and
`mechanism of action,” or “(2) a Bachelor’s or Master’s degree in chemistry or a
`closely related field with significant experience in an academic or industrial
`laboratory focusing on drug discovery and/or development for the treatment of
`viral diseases.” Pet. 6.
`Patent Owner “takes no position on Petitioner’s proposed definition of a”
`person of ordinary skill in the art (“POSA”), but indicates that “a POSA also would
`include, or would have access to, an individual with an M.D. who has experience
`developing or researching antiviral treatment methods, such as treatment for HCV,
`or experience treating viral infections such as HCV.” Prelim. Resp. 10.
`On this record, for purposes of this Decision, we accept Petitioner’s
`definition without the clarification advanced by Patent Owner. Specifically, based
`in the information presented, we find that a person of ordinary skill in the art
`would have either (1) a Ph.D. in chemistry or a closely related field with some
`experience in an academic or industrial laboratory focusing on drug discovery or
`development, and would also have some familiarity with antiviral drugs and their
`design and mechanism of action, or (2) a Bachelor’s or Master’s degree in
`chemistry or a closely related field with significant experience in an academic or
`industrial laboratory focusing on drug discovery and/or development for the
`treatment of viral diseases. On that point, however, we agree with Patent Owner
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`that the outcome of this Decision would be the same “regardless of which
`definition applies.” Prelim. Resp. 10.
`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 (Fed. Cir. 1985)).
`Claim Construction
`B.
`In an inter partes review, 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. § 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 that standard, and absent any special definitions, we generally give claim
`terms their ordinary and customary meaning, as would be understood by one of
`ordinary skill in the art at the time of the invention. See In re Translogic Tech.,
`Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). 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).
`Neither Petitioner nor Patent Owner raises any claim construction issues or
`proposed constructions, and both acknowledge that the claim terms should be
`given their ordinary and customary meaning. Pet. 6–7; Prelim. Resp. 10–11.
`Accordingly, we apply the ordinary and customary meaning to the claims at issue.
`See Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co. Ltd., 868 F.3d 1013,
`1017 (Fed. Cir. 2017) (“[W]e need only construe terms ‘that are in controversy,
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`and only to the extent necessary to resolve the controversy’” (quoting Vivid Techs.,
`Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999))).
`C. Principles of Law
`Anticipation requires that “each and every element as set forth in the claim is
`found, either expressly or inherently described, in a single prior art reference.” In
`re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999) (citation omitted). “To establish
`inherency, the extrinsic evidence ‘must make clear that the missing descriptive
`matter is necessarily present in the thing described in the reference.’” Id. (quoting
`Continental Can Co. v. Monsanto Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991)).
`Obviousness “requires a suggestion of all limitations in a claim.” CFMT,
`Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003) (citing In re
`Royka, 490 F.2d 981, 985 (CCPA 1974)). “In determining whether obviousness is
`established by combining the teachings of the prior art, the test is what the
`combined teachings of the references would have suggested to those of ordinary
`skill in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal
`quotations omitted).
`“An obviousness determination requires finding both ‘that a skilled artisan
`would have been motivated to combine the teachings of the prior art . . . and that
`the skilled artisan would have had a reasonable expectation of success in doing
`so.’” In re Stepan Co., 868 F.3d 1342, 1345–46 (Fed. Cir. 2017) (quoting
`Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367–68
`(Fed. Cir. 2016)).
`A conclusion of obviousness “cannot be sustained by mere conclusory
`statements; instead, there must be some articulated reasoning with some rational
`underpinning to support the legal conclusion of obviousness.” KSR Int’l Co. v.
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`Teleflex Inc., 550 U.S. 398, 418 (2007) (quoting In re Kahn, 441 F.3d 977, 988
`(Fed. Cir. 2006)).
`We analyze the asserted grounds of unpatentability in accordance with the
`above-stated principles.
`Anticipation by and obviousness over Legrand-Abravanel
`D.
`Petitioner asserts that claims 1–4 are anticipated by, and obvious over,
`Legrand-Abravanel. Pet. 19–22. On this record, we determine that Petitioner has
`not established a reasonable likelihood that it would prevail in showing that any of
`claims 1–4 are anticipated by, or obvious over, Legrand-Abravanel.
`Legrand-Abravanel (Ex. 1005)
`1.
`Legrand-Abravanel relates to new NS5B polymerase inhibitors for hepatitis
`C, and states that “NS5B polymerase inhibitors will form an integral part of more
`effective anti-HCV therapy, in combination with interferon or with other directly
`acting antiviral agents.” Ex. 1005, 1. Legrand-Abravanel identifies a number of
`new inhibitors of the HCV polymerase by drug name, including PSI-7851. Id. at 3
`(Table 1). Legrand-Abravanel also states that “[s]everal new antiviral compounds
`are in development and could be associated with polymerase inhibitors,” and
`identifies “NS5A inhibitors” among several classes of compounds. Id. at 9.
`Analysis
`2.
`Petitioner argues that Compound 10 was already known and that Legrand-
`
`Abravanel “discloses Compound 10 when referring to the compound names PSI-
`7851 and PSI-7977.” Pet. 21. Furthermore, Petitioner argues that “NS5A
`inhibitors (the class of compound which Compound 6 falls within) were also
`known to be useful for treating HCV in combination with other antiviral agents
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`such as nucleotide inhibitors of NS5B polymerase. See Serrano-Wu (EX1007),
`Simmen (EX1008) and Pockros (EX1009); EX1012 ¶71.”6 Pet. 21.
`
`Petitioner further asserts that Legrand Abravanel “taught that NS5B
`polymerase inhibitors will form an integral part of more effective anti-HCV
`therapy, in combination with interferon or with other directly acting antiviral
`agents,” and “highlighted that nucleos(t)ide inhibitors PS-7851and PSI-7977
`(Compound 10 in the ‘256 patent) had been selected for further clinical
`development.” Id. at 21–22, citing Ex. 1005, 1, 4–5 and Ex. 1012 ¶¶ 72, 73.
`
`Based on the foregoing, Petitioner concludes that
`due to the resistant mutations of HCV to nucleos(tide) analogues,
`Legrand-Abravanel taught that combination therapy with small
`molecule inhibitors and without IFN (interferon) was the ultimate goal
`and should be studied early with innovative drug development
`approaches. EX1012 ¶74. Legrand-Abravanel further suggested that
`several new antiviral compounds were in development and could be
`associated with polymerase inhibitors, including NS5A inhibitors.
`EX1005 at 9; EX1012 ¶74.
`
`
`Taking into account the background knowledge in the art and the
`teachings of Legrand-Abravanel, claims 1-4 of ’256 were anticipated
`and obvious. EX1012 ¶75. In particular, Legrand-Abravanel taught,
`or at least suggested, combination therapies to treat HCV without
`administering interferon, and which may or may not include ribavirin.
`Id. Moreover, Legrand-Abravanel inherently taught the combination
`of NS5A inhibitors, such as Compound 6, with polymerase inhibitors
`such as Compound 10. Id. Legrand-Abravanel, therefore, anticipated
`claims 1-4 of the ’256 patent, or at minimum rendered them obvious.
`Id.
`Pet. 22.
`
`6 Citations to Exhibit 1012 are to paragraphs of the Fortunak Declaration that
`restate the allegations in the Petition without citation to any additional evidentiary
`support.
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`Patent Owner responds that Legrand-Abravanel does not expressly or
`inherently disclose compounds 6 and 10, or their combination without interferon
`(Prelim. Resp. 18–24), and that Petitioner “does not address key claim limitations
`missing from the prior art and provides no reason, motivation, or reasonable
`expectation of success in arriving at the claimed interferon-free combination
`therapy for HCV” (id. at 24–32).
`We separately address Petitioner’s challenges based on anticipation and
`obviousness.
`Anticipation
`
`Petitioner’s anticipation challenge is based on the contention that Legrand-
`Abravanel’s disclosure of compounds named PS-7851and PSI-7977 is a disclosure
`of claimed compound 10 (a nucleotide inhibitor of NS5B polymerase), and that the
`disclosed NS5B polymerase inhibitors may be combined with an NS5A inhibitor,
`the class of compounds that includes compound 6, without administering
`interferon. Pet. 21–22. Moreover, according to Petitioner, “Legrand-Abravanel
`inherently taught the combination of NS5A inhibitors, such as Compound 6, with
`polymerase inhibitors such as Compound 10.” Id. at 22.
`
`Assuming that Legrand-Abravanel discloses the combination of an NS5B
`inhibitor, such as compound 10, with another antiviral agent (without interferon),
`the issue remains whether Legrand-Abravanel discloses compound 6 as that other
`antiviral agent, as well as disclosing the combination of compound 6 with
`compound 10. See Robertson, 169 F.3d at 745. Petitioner supports its assertion
`that Legrand-Abravanel discloses compound 6 by asserting that compound 6 is an
`NS5A inhibitor and pointing to the statement in Legrand-Abravanel that “[s]everal
`new antiviral compounds are in development and could be associated with
`polymerase inhibitors: NS3 protease inhibitors [], NS3 helicase inhibitors [], p7
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`inhibitors [], NS5A inhibitors [], cyclophilin inhibitors [], and immunomodulators
`[]. This represents a huge field for investigation.” Ex. 1005, 9 (cited at Pet. 22).
`
`Patent Owner argues that to establish anticipation of a species by a generic
`disclosure in the prior art, a POSA must “‘at once envisage’ the claimed
`arrangement or combination” upon review of that prior art. Prelim. Resp. 19
`(citing Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed.
`Cir. 2015) (citation omitted)). Patent Owner further contends that a POSA could
`not “at once envisage” compound 6 from the disclosure of Legrand-Abravanel. Id.
`
`“[A] disclosed genus may anticipate a claimed species when the genus is so
`small that one of ordinary skill in the art would ‘at once envisage each member of
`this limited class.’” Wasica Fin. GmbH v. Continental Auto. Sys., Inc., 853 F.3d
`1272, 1285 (Fed. Cir. 2017) (quoting AbbVie Inc. v. Mathilda & Terence Kennedy
`Inst. of Rheumatology Tr., 764 F.3d 1366, 1379 (Fed. Cir. 2014)). Here, Legrand-
`Abravanel discloses a genus comprising the combination of an NS5B inhibitor
`(such as compound 10) and a compound within a group of classes of compounds,
`that mentions NS5A inhibitors as one class of compounds. Ex. 1005, 9.
`
`Petitioner states that “Legrand-Abravanel inherently taught the combination
`of NS5A inhibitors, such as Compound 6, with polymerase inhibitors such as
`Compound 10” (Pet. 22), but does not address whether or how a person of ordinary
`skill in the art would at once envisage each member of the genus disclosed by
`Legrand-Abravanel, including the combination of compound 10 and compound 6
`without interferon. For example, Petitioner does not identify the size of any genus
`or the specific species that fall with that genus, other than the conclusory statement
`that Legrand-Abravanel “inherently” taught the combination of compounds 6 and
`10. That is not sufficient. See Wasica, 853 F.3d 1285–86 (discussing the failure of
`the IPR petition to set forth the factual components regarding the genus/species
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`anticipation analysis). Furthermore, we agree with Patent Owner that the mere
`mention of “NS5A inhibitors” in Legrand-Abravanel does not establish that a
`POSA would at once envisage compound 6 or that compound 6 is “necessarily
`present” in Legrand-Abravanel. Prelim. Resp. 19–20; see Robertson, 169 F.3d at
`745. Moreover, “anticipation is not proven by ‘multiple, distinct teachings that the
`artisan might somehow combine to achieve the claimed invention.’” Microsoft
`Corp. v. Biscotti, Inc., 878 F.3d 1052, 1069 (Fed. Cir. 2017) (affirming that the
`quoted statement by the Board was correct). Petitioner, thus, fails to establish
`sufficiently that Legrand-Abravanel discloses compound 6, or the combination of
`compound 6 with compound 10.
`Therefore, Petitioner fails to show sufficiently that Legrand-Abravanel
`discloses each and every element of claim 1, either expressly or inherently. See
`Robertson, 169 F.3d at 745. Accordingly, we determine that Petitioner has not
`shown a reasonable likelihood that it would prevail on its assertion that claim 1
`(and dependent claims 2–4, which include the limitations of claim 1) are
`anticipated by Legrand-Abravanel.
`Obviousness
`Petitioner relies on the same arguments advanced in connection with the
`anticipation challenge for the challenge of claims 1–4 as obvious over Legrand-
`Abravanel. Pet. 19–22. As to specific statements regarding obviousness based on
`Legrand-Abravanel, Petitioner argues that “[c]laims 1–4 were also obvious over
`Legrand-Abravanel because a POSA would have been motivated to take the
`teachings in Legrand-Abravanel and arrive at the combination of anti-viral agents
`for treating HCV claimed in the ’256 patent,” “claims 1–4 of ’256 were . . .
`obvious,” and “Legrand-Abravanel . . . at minimum rendered [claims 1–4]
`obvious.” Pet. 19–20, 22. The Petition also includes an introductory paragraph
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`prior to addressing the alleged grounds of unpatentability wherein Petitioner states
`that “a POSA would have been motivated to modify the references as discussed
`below and had a reasonable expectation of success of arriving at the claims of the
`’256 patent.” Pet. 19. That sentence cites to a paragraph of the Fortunak
`Declaration which repeats the same statement without citing any evidentiary
`support. See Ex. 1012 ¶ 66.
`Patent Owner argues, in part, that “Petitioner’s tacked-on obviousness
`challenge relies on conclusory statements, rather than any actual obviousness
`analysis, and fails to show why a POSA would have arrived at the claimed
`interferon-free combination from Legrand-Abravanel’s teachings, with a
`reasonable expectation of success.” Prelim. Resp. 17. In further regard to the
`reasonable expectation of success requirement, Patent Owner argues that
`“Legrand-Abravanel only generally suggests thousands of possible combinations
`to explore, without any teaching or guidance as to which one, if any, would result
`in a successful HCV treatment.” Id. at 29.
`Among other requirements, an obviousness determination requires a
`showing that a skilled artisan “would have had a reasonable expectation of
`success” in combining the teachings of the prior art.7 Stepan, 868 F.3d at 1346.
`Moreover, this requirement refers to whether the skilled artisan would have had a
`reasonable expectation of success in combining the teachings of the prior art “to
`achieve the claimed invention.” Intelligent Bio-Sys., 821 F.3d at 1367–68 (citing
`cases).
`
`
`7 The requirement to establish a reasonable expectation of success is also
`applicable where there is a single prior art reference. Stepan, 868 F.3d at 1346, n1.
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`Here, Petitioner provides no analysis of the reasonable expectation
`requirement, and relies solely on conclusory statements that are insufficient to
`establish obviousness. See KSR, 550 U.S. at 418. The argument that “a POSA
`would have been motivated to take the teachings in Legrand-Abravanel and arrive
`at the combination of anti-viral agents for treating HCV claimed in the ’256
`patent” (Pet. 19–20) is not sufficient because reasonable expectation of success and
`motivation to combine are two different legal concepts. See Intelligent Bio-Sys.,
`821 F.3d at 1367. Furthermore, we find that Legrand-Abravenel’s statement that
`“[s]everal new antiviral compounds are in development and could be associated
`with polymerase inhibitors,” followed by a list of multiple classes of compounds
`and the statement “[t]his represents a huge field for investigation,” teaches (at
`most) a general approach and guidance to a field of experimentation that is thus
`insufficient to establish a reasonable expectation of success. See Medichem, S.A. v.
`Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) (“prior art fails to provide the
`requisite ‘reasonable expectation’ of success where it teaches merely to pursue a
`‘general approach that seemed to be a promising field of experimentation, where
`the prior art gave only general guidance as to the particular form of the claimed
`invention or how to achieve it.’”) (quoting In re O’Farrell, 853 F.2d 894, 903
`(Fed. Cir. 1988)).
`On this record, we find that Petitioner has failed to show sufficiently
`whether or why a skilled artisan would have had a reasonable expectation of
`success in combining the teachings of Legrand-Abravanel to achieve the invention
`of claim 1 of the ’256 patent. Accordingly, we determine that Petitioner has not
`shown a reasonable likelihood that it would prevail on its assertion that claim 1,
`and, thus, dependent claims 2–4, which include the limitations of claim 1, are
`unpatentable as obvious over Legrand-Abravanel. See In re Fine, 837 F.2d 1071,
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`1076 (Fed. Cir. 1988) (“Dependent claims are nonobvious under section 103 if the
`independent claims from which they depend are nonobvious.”).
`Anticipation by Delaney
`E.
`Petitioner contends that claims 1–4 are anticipated by Delaney. Pet. 22–26.
`On this record, we determine that Petitioner has not established a reasonable
`likelihood that it would prevail in showing that any of claims 1–4 are anticipated
`by Delaney.
`
` Delaney (Ex. 1010)
`1.
`Delaney teaches “a dosing regimen for the treatment of HCV comprising:
`
`administering one or more anti-HCV compound or a pharmaceutically acceptable
`salt thereof; and ribavirin, but not one or more interferon.” Ex. 1010 ¶ 12.
`Delaney further teaches that
`non-limiting examples of suitable combinations include combinations
`of one or more compounds with one or more additional therapeutic for
`HCV treatment including HCV NS3 protease inhibitors, alpha-
`glucosidase 1 inhibitors, hepatoprotectants, nucleoside or nucleotide
`inhibitors of HCV NS5B polymerase, non-nucleoside inhibitors of
`HCV NS5B polymerase, HCV NS5A inhibitors, TLR-7 agonists,
`cyclophillin
`inhibitors, HCV IRES
`inhibitors, pharmacokinetic
`enhancers, as well as other drugs for treating HCV.
`
`Id. ¶ 74. Delaney specifically identifies PSI-7851 and PSI-7977 among a list of
`compounds that may be included in those groups of compounds. Id. Delaney
`discloses several examples of its anti-HCV compounds, including compound 16,
`which corresponds to compound 6 as claimed. Id. at 49; Prelim. Resp. 34.
`Delaney was cited during prosecution of the ’256 patent. Ex. 1001, 3.
`Analysis
`2.
`Petitioner argues that compound 10 was already known, and that “Delaney
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`specifically taught that one or more of its compounds may be combined with one
`or more compounds selected from a group including the nucleos(t)ide inhibitors of
`HCV NS5B polymerase, PSI-7851 and PSI-7977 (Compound 10 in ’256).”
`Pet. 25, citing Ex. 1010 ¶¶ 74, 75 and Ex. 1012 ¶82.8 Petitioner also argues that
`“one of the compounds taught in Delaney that could be combined with PSI-7851 or
`PSI-7977 is [Compound 6].” Id. at 25–26. Petitioner concludes that:
`Delaney thus taught the combination of Compound 10 with Compound
`6 wherein the dosage regimen for the method of treatment of HCV did
`not include interferon, but could include the administration of ribavirin.
`EX1012 ¶84. Delaney further taught non-limited examples of suitable
`combinations included combinations of one or more compounds with
`one or more additional therapeutic [agents] for HCV treatment
`including nucleos(t)ide inhibitors of HCV NS5B polymerase and NS5A
`inhibitors, but which implicitly could exclude ribavirin. Id. Therefore,
`Delaney anticipated claims 1-4 of the ’256 patent. Id.
`Id. at 26.
`
`Patent Owner asserts that “Delaney does not disclose the specific
`combination of compounds 6 and 10 as claimed,” and reasserts its argument,
`advanced with respect to Legrand-Abravanel, that a patent challenger must prove
`that a POSA would “at once envisage” the claimed arrangement or combination for
`a generic disclosure in the prior art to anticipate a specific combination. Prelim.
`Resp. 32–36.
`
`Our analysis with respect to the anticipation challenge based on Legrand-
`Abravanel is equally applicable here, and we adopt that analysis as to the
`
`
`8 As stated above in connection with the challenge based on Legrand-Abravanel, all
`of the citations to Ex. 1012 are to paragraphs of the Fortunak Declaration that
`restate the allegations in the Petition without citation to any additional evidentiary
`support.
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`Case IPR2018-00211
`Patent 9,393,256 B2
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`anticipation challenge based on Delaney. Although Petitioner describes Delaney’s
`broad generic disclosure of numerous combinations of compounds (such as
`compound 6) with other compounds, Petitioner does not explain whether or how a
`person of ordinary skill would at once envisage each member of that large genus,
`including the combination of compound 10 and compound 6 without interferon.
`See Wasica, 853 F.3d 1285–86. Rather, Petitioner simply concludes that “Delaney
`. . . taught the combination of Compound 10 with Compound 6 . . . [that] did not
`include interferon.” Pet. 26. That bare argument is not sufficient to establish
`anticipation. See Microsoft, 878 F.3d at 1069.
`Thus, Petitioner fails to show sufficiently that Delaney discloses each and
`every element of claim 1, either expressly or inherently. See Robertson, 169 F.3d
`at 745. Accordingly, we determine that Petitioner has not shown a reasonable
`likelihood that it would prevail on its assertion that claim 1 (and dependent
`claims 2–4, which include the limitations of claim 1) are anticipated by Delaney.
`F. Obviousness over Sofia ’634 and Guo
`Petitioner contends that claims 1–4 are obvious over Sofia ’634 and Guo.
`Pet. 26–30. On this record, we determine that Petitioner has not established a
`reasonable likelihood that it would prevail in showing that any of claims 1–4 are
`obvious over Sofia ’634 and Guo.
`1. Sofia ’634 (Ex. 1004)
`Sofia ’634 describes nucleoside phosphoramidates and their use as agents
`for treating viral diseases, such as hepatitis C virus (HCV) infection. Ex. 1004,
`2:15–21. For example, compound 25 of Sofia ’634 is claimed compound 10. Id. at
`696; Prelim. Resp. 15. Sofia ’634 teaches a method of treatment comprising
`administering a described nucleoside phosphoramidate and another antiviral agent.
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`Case IPR2018-00211
`Patent 9,393,256 B2
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`Id. at 666. Sofia ’634 was cited during prosecution of the ’256 patent. Ex. 1001,
`4.
`
`Guo (Ex. 1011)
`2.
`Guo teaches “pharmaceutical compositions comprising a compound of the
`present invention . . . in combination with at least one additional therapeutic agent
`selected from the group consisting of” an extensive list of compounds that includes
`PSI-6130. Ex. 1011, 29. One of the NS5A inhibitor compounds taught by Guo is
`Compound 6. Id. at 673, 984. Guo was cited during prosecution of the ’256
`patent. Ex. 1001, 4.
`
`Analysis
`3.
`Petitioner argues that Sofia ’634 taught claimed compound 10, that
`nucleotide NS5B polymerase inhibitors “could be directed to a method of
`treatment in combination with another antiviral agent,” and that examples of
`another antiviral agent included NS5A inhibitors. Pet. 28. Petitioner also argues
`that Guo taught NS5A inhibitor compounds, including claimed compound 6, and
`that compounds of its invention could be combined with nucleos(t)ide inhibitors of
`HCV NS5B polymerase, such as PSI-6130. Id. at 29. Petitioner concludes that:
`A POSA would have been motivated by the teachings of Sofia ’634 and
`Guo, along with the existing background knowledge in the art, to
`combine the respective compounds claimed therein for treating HCV.
`EX1012 ¶94. A POSA would have also been motivated to test such
`compound combinations with or without an interferon and ribavirin for
`the purpose of assessing antiviral effectiveness and any viral resistance.
`Id. Accordingly, given the extensive knowledge in the art around
`direct-acting antiviral compounds for treating HCV, and the teachings
`of Sofia ’634 and Guo, it would have been obvious to a POSA to arrive
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`Patent 9,393,256 B2
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`at claims 1-4 of the ’256 patent. Id. Therefore, Sofia ’634 and Guo
`rendered claims 1-4 of the ’256 patent obvious. Id.9
`Id. at 29–30.
`Patent Owner argues that “Petitioner fails to identify in the prior art any
`teaching of the claim limitation requiring interferon-free treatment of HCV
`infection in a human,” and that Petitioner has failed to provide a sufficient
`explanation of “why a POSA would have had a reasonable expectation of success”
`in combining Sofia ’634 and Guo to achieve the claimed invention. Prelim.
`Resp. 37–38. In regard to the reasonable expectation of success requirement,
`Patent Owner asserts that “Petitioner’s Ground 3 obviousness challenge never even
`contends that a POSA would have had a reasonable expectation of success in
`achieving the claimed invention,” and that “[t]he only mention of