Trials@uspto.gov
`Tel: 571-272-7822
`
`
`
`
`Paper No. 9
`Entered: May 24, 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 IPR2018-00125
`Patent 8,633,309 B2
`_______________
`
`
`Before LORA M. GREEN, ERICA A. FRANKLIN, 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 IPR2018-00125
`Patent 8,633,309 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 1–12
`of U.S. Patent 8,633,309 B2 (the “’309 patent”). 35 U.S.C. § 311. Gilead
`Pharmasset LLC (“Patent Owner”) filed a Preliminary Response to the Petition
`(Paper 6), as corrected (Paper 8). (“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 ’309 patent. Therefore,
`we do not institute an inter partes review for any challenged claim of the ’309
`patent.
`
`Related Proceedings
`A.
`Petitioner 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); and one petition for inter partes review of U.S. Patent
`No. 9,284,342 (Case No. IPR2018-00126). Pet. 2; Paper 3, 3.
`
`
`The ’309 Patent
`B.
`The ’309 patent relates to nucleoside phosphoramidates and their use as
`agents in treating viral diseases, such as hepatitis C. Ex. 1001, 1:12–17. The ’309
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`patent specifically disclose a compound represented by formula 4 and its respective
`phosphorous-based diastereomers represented by formulas Sp-4 and Rp-4, as
`shown below:
`
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`Id. at 4:50–5:24. The ’309 patent states that “[t]he term ‘P*’ means that the
`phosphorus atom is chiral and that it has a corresponding Cahn-Ingold-Prelog
`designation of ‘R’ or ‘S’ which have their accepted meanings.” Id. at 6:8–10.
`The compound of formula Sp-4 is sofosbuvir. Prelim. Resp. 10.
`The ’309 patent discloses methods of synthesizing the formula 4 compound
`as a diastereomeric mixture of SP-4 and RP-4. Ex. 1001, 31:60–33:56. The ’309
`patent also discloses methods of obtaining substantially pure SP-4 from the mixture
`of diastereomers by chromatography and crystallization of the individual
`stereoisomers. Id. at 36:3–12 (describing crystallization process that resulted in
`“>99% pure SP-4”); id. at 72:34–61 (describing HPLC purification conditions that
`resulted in 99.5% pure SP-4). The ’309 patent teaches methods of generating
`substantially pure isomers by diastereoselective synthesis. See, e.g., id. at 49:25–
`50:7 (describing processes for stereoselective synthesis of the SP-4 enantiomer,
`resulting in about 97% chiral purity). The ’309 patent also describes biological
`activity tests in which the potency of each of the compounds of formula 4, RP-4,
`and SP-4 was demonstrated by viral replicon assays. See id. at 75:30–56.
`
`The ’309 patent states that “U.S. patent application Ser. No. 12/053,015,
`which corresponds to WO 2008/121634 [Sofia ’634, Ex. 1005] . . . discloses a
`number of phosphoramidate nucleoside prodrugs, many of which show activity in
`an HCV assay.” Id. at 4:42–46.
`
`
`
`
`Illustrative Claim
`C.
`Petitioner challenges claims 1–12 of the ’309 patent, of which claim 1 is the
`only independent claim. Claim 1 is reproduced below:
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`1. A compound represented by the formula (4):
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`Ex. 1001, 76:1–47.
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`Claims 2–12 depend directly or indirectly on claim 1. Id. at 76:48–77:12.
`
`
`
`
`
`The Asserted Grounds of Unpatentability
`D.
`Petitioner contends that the challenged claims are unpatentable under 35
`U.S.C. §§ 102(a) and 103(a) based on the following specific grounds. Pet. 3.
`Reference[s]
`Basis
`Claims challenged
`Sofia ’6341
`§ 102(a)
`1–12
`
`Sofia ’634 and Congiatu2
`
`§ 103(a)
`
`Clark ’1473 and Congiatu
`
`§103(a)
`
`1–12
`
`1–12
`
`
`Petitioner also relies on the Declaration of Joseph M. Fortunak, Ph.D.
`Ex. 1002.
`
` 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
`
`
`1 Sofia et al., WO 2008/121634 A2, published Oct. 9, 2008 (“Sofia ’634”). Ex.
`1005. Sofia ’634 is the PCT publication corresponding to US Application Serial
`No. 12/053,015, which issued as US Patent No. 7,964,580 B2 on June 21, 2011
`(“the ’580 patent”). See Ex. 1001, col. 4, ll. 42–43.
`2 C. Congiatu et al., Novel Potential Anticancer Naphthyl Phosphoramidates of
`BVdU: Separation of Diastereoisomers and Assignment of the Absolute
`Configuration of the Phosphorus Center, J. MED. CHEM. 49, 452–55 (2006)
`(“Congiatu”). Ex. 1006.
`3 Clark, WO 2005/003147 A2, published Jan. 13, 2005 (“Clark ’147”). Ex. 1007.
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`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. 9.
`Patent Owner’s definition of a person of ordinary skill in the art differs from
`Petitioner’s definition. Prelim. Resp. 15. Patent Owner contends 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 industry laboratory focusing
`on drug discovery or development, including compound purification,” and “would
`have some familiarity with the development of antiviral drugs, or work in
`collaboration with someone who has expertise in the development of antiviral
`drugs;” 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, including compound purification,” and “some familiarity with
`development of antiviral drugs, or work in collaboration with someone who has
`expertise in the development of antiviral drugs.” Id.
`On this record and at this stage of the proceeding, we do not discern an
`appreciable difference in the parties’ respective definitions of a person of ordinary
`skill in the art. Accordingly, 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,
`including (for example) compound purification, 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
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`discovery and/or development, including (for example) compound purification, for
`the treatment of viral diseases.
`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 raise any claim construction issues or
`proposed constructions, and both acknowledge that the claim terms should be
`given their ordinary and customary meaning. Pet. 9–10; Prelim. Resp. 15–16.
`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.
`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).
`Obviousness also requires “a reason that would have prompted a person of
`ordinary skill in the relevant field to combine the elements in the way the claimed
`new invention does.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). 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.” Id. (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.
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`Anticipation by Sofia ’634
`D.
`Petitioner asserts that claims 1–12 are anticipated by Sofia ’634. Pet. 27–35.
`On this record, we determine that Petitioner has not established a reasonable
`likelihood that it would prevail in showing that any of claims 1–12 are anticipated
`by Sofia ’634.
`
`Sofia ’634 (Ex. 1005)
`1.
`Sofia ’634 discloses phosphoramidate prodrugs of nucleoside derivatives
`represented by formula (I):
`
`
`Ex. 1005, Abstract. Sofia ’634 further describes nucleoside phosphoramidates and
`their use as agents for treating viral diseases, such as hepatitis C virus (HCV)
`infection. Id. at 2:15–21. Example 25 of Sofia ’634 is the same as that represented
`by formula (4) in the ’309 patent, except that Example 25 is a mixture of
`diastereomers at phosphorus. Id. at 684. Example 81 of Sofia ’634 describes the
`separation of diastereomeric mixtures of Examples 15, 39, and 49. Id. at 693–94.
`Sofia ’634 is referenced in the ’309 patent. Ex. 1001, 4:42–46.
`Analysis
`2.
`Petitioner argues that “Example 25 in Sofia ’634 is the same compound as
`that represented by formula (4) in claim 1 of the ’309 patent,” but also
`acknowledges that “Example 25 is a mixture of diastereomers at phosphorous.”
`Pet. 29–30. Moreover, rather than pointing to any disclosure in Sofia ’634 of the
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`separation of the diastereomers of Example 25, Petitioner argues that “[a] POSA
`would also expect that the specific disclosures of Examples 15, 39, and 49 would
`apply to Example 25,” because “each of [compounds 15, 39, and 49] is a slightly
`different phosphoramidate prodrug analog” as compared to “the compound
`claimed in the ’309 patent and each is a close structural analog of Example 25.”
`Id. at 30–31. Notably, such argument by Petitioner does not establish that the
`compound claimed in the ’309 patent is disclosed by Sofia ’634 as required for a
`finding of anticipation. See Robertson, 169 F.3d at 745.
`Regarding the limitations in claim 1 that “the compound is at least 97% of
`the Spstereoisomer represented by the formula (Sp-4)” and “not more that 3% of
`the Rpstereoisomer represented by the formula (Rp-4),” Petitioner contends that
`“these arbitrary limits are inherently taught by Sofia ’634” and “are not meaningful
`from a standpoint of antiviral activity.” Pet. 33. Petitioner provides no support for
`those arguments, other than a reference to the Fortunak Declaration that repeats the
`same words as Petitioner, but without citation to any evidentiary support. Ex. 1002
`¶ 94. In particular, Petitioner makes no showing that any allegedly inherent
`limitations in claim 1 are “necessarily present” in Sofia ’634. See Robertson, 169
`F.3d at 745; In re Oelrich, 666 F.2d 578, 581 (CCPA 1981) (“Inherency . . . may
`not be established by probabilities or possibilities. The mere fact that a certain
`thing may result from a given set of circumstances is not sufficient.”) (citation
`omitted).
`Thus, Petitioner fails to persuasively establish that Sofia ’634 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
`2–12, which include the limitations of claim 1) are anticipated by Sofia ’634.
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`E. Obviousness over Sofia ’634 and Congiatu
`Petitioner contends that claims 1–12 are obvious over Sofia ’634 and
`Congiatu. Pet. 35–45. For the reasons set forth below, we exercise our discretion
`to decline institution because the same or substantially the same prior art or
`arguments were previously presented to the Office. See 35 U.S.C. § 325(d) (“In
`determining whether to institute or order a proceeding under this chapter . . . the
`Director may take into account whether, and reject the petition or request because,
`the same or substantially the same prior art or arguments previously were
`presented to the Office.”).4
`
`Prosecution History
`1.
`The Examiner rejected issued claims 1–125 as obvious over Sofia 2007,6
`finding that Sofia 2007 taught a phosphoramidate prodrug that is a mixture of Sp
`and Rp stereoisomers, and is a potent therapeutic agent for treating HCV infection.
`Pet. 6; Ex. 1004, 9–13. The Examiner further found that Sofia 2007 does not
`expressly teach that the Sp stereoisomer is at least 97%, 98%, or 99% and the Rp
`stereoisomer is not more than 3%, 2%, or 1%. Pet. 6; Ex. 1004, 12. The Examiner
`concluded that:
`
`
`4 Petitioner does not specifically address Section 325(d). However, Patent Owner
`argues that institution should be denied based on Sofia ’634 and Congiatu pursuant
`to 35 U.S.C. § 325(d). Prelim. Resp. 48–50.
`5 Issued claims 1–12 were numbered claims 82–93 during prosecution. Ex. 1004,
`4–5.
`6 Sofia, M.J., beta-D-2′-Deoxy-2′-fluoro-2′-C-methyluridine Phosphoramidates:
`Potent and Selective Inhibitors of HCV RNA Replication, 2nd International
`Workshop on HCV—Resistance and New Compounds, Oct. 31, 2007 (“Sofia
`2007”). Petitioner did not submit a copy of Sofia 2007, but Sofia 2007 appears
`from the record to include this paper and/or a corresponding poster (#7) exhibited
`at the referenced workshop.
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`It would have been obvious to one of ordinary skill in the art at
`the time the invention was made to separate the mixture of Sp and Rp
`stereoisomers and formulate it into a pharmaceutical composition for
`treating HCV infection.
`
`
`One having ordinary skill in the art at the time the invention was
`made would have been motivated to separate the mixture of Sp and Rp
`stereoisomers and formulate it into a pharmaceutical composition for
`treating HCV infection because the disclosed phosphoramidate prodrug
`containing a mixture of Sp and Rp isomers is known to have potential
`therapeutic effect and usefulness in treating HCV infection, and
`separation [of] the two isomers of a known therapeutic drug and
`identifying the therapeutic potency of each isomer are well known in
`the art. One of ordinary skill in the art would have reasonably expected
`[] success because separating the isomers of the known therapeutic
`agents and identifying the potency of each isomer and formulat[ing]
`into a pharmaceutical composition is well within the ordinary and
`routine level of one skilled in the art.
`Pet. 6–7; Ex. 1004, 12–13.
`
`Patent Owner contested the rejection and, according to Petitioner, argued (in
`part) that “neither [Sofia 2007] nor any other cited reference supported the
`assertion that one skilled in the art would have been motivated to separate the Rp
`and Sp stereoisomers and obtain compounds of at least 97%, 98% and 99% of the
`Sp stereoisomer.” Pet. 7. Patent Owner also argued “unexpected results,”
`particularly that “the Sp stereoisomer (Sp-4) is more potent [than] the mixture of
`the two phosphorous-based stereoisomers (4) and > 20-fold more potent than the
`corresponding Rp stereoisomer (Rp-4).” Ex. 1004, 24; Pet. 7–8. The Examiner
`replied:
`Applicant’s arguments, submitted May 21, 2013, with respect to the
`rejection of instant claims 82-93 under 35 USC 103(a) for being
`obvious over [Sofia 2007], have been fully considered and found to be
`persuasive to remove the rejection as Applicant has demonstrated that
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`the enantiomer Sp-4 is unexpectedly more potent in inhibiting HCV
`replication than the Rp-4 enantiomer, thereby overcoming the prima
`facie case of obviousness.
`Pet. 8; Ex. 1004, 39.
`In the Reasons for Allowance, the Examiner said:
`
`The claimed invention is novel and non-obvious over the prior art.
`While it is known in the art to make phosphoramidate compounds such
`as the instantly claimed ones, for example as described in [the ’580
`patent] and furthermore to resolve chiral compounds into individual
`enantiomers, Applicant has discovered that the Sp enantiomer of the
`claimed compound is unexpectedly more potent in inhibiting HCV
`replication as disclosed on p. 97 of the specification as originally filed.
`Therefore any prima facie case of obviousness is overcome by this
`finding of unexpected results. For these reasons the claims meet the
`requirements of 35 USC 102 and 103.
`Pet. 8; Ex. 1004, 56.
`
`Therefore, as indicated in the prosecution history, the Examiner found
`that it was known in the art to make phosphoramidate compounds (for
`example as described in the ’580 patent, the US counterpart to Sofia ’634),
`and to resolve chiral compounds into individual enantiomers. Id.
`Analysis
`2.
`When evaluating whether the same or substantially the same prior art or
`arguments were previously presented to the Office under § 325(d), the Board has
`considered a number of non-exclusive factors, including, for example: (1) the
`similarity of the asserted art and the prior art involved during the examination; (2)
`the extent to which the asserted art was considered during examination, including
`whether the prior art was the basis for rejection; (3) the cumulative nature of the
`asserted art and the prior art considered during examination; (4) whether Petitioner
`has pointed out sufficiently how the Examiner erred in its consideration of the
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`asserted prior art; (5) the extent of the overlap between the arguments made during
`examination, and the manner in which Petitioner relies on the prior art or the
`applicant’s arguments during examination; and (6) the extent to which additional
`evidence and facts presented in the Petition warrant reconsideration of the asserted
`prior art. Juniper Networks, Inc. v. Mobile Telecomm’ns Techs., LLC, Case
`IPR2017-00642, slip op. at 8–9 (PTAB July 27, 2017) (Paper 24); see also Becton,
`Dickinson & Co. v. B. Braun Melsungen AG, Case IPR2017-01586, slip op. at 17–
`28 (PTAB Dec. 15, 2017) (Paper 8) (informative). After considering these factors,
`we are persuaded that the Petition presents substantially the same prior art or
`arguments previously presented to the Office with respect to the asserted grounds
`of obviousness based on Sofia ’634 and Congiatu. See 35 U.S.C. § 325(d).
`Petitioner’s Arguments
`Petitioner states that “[d]uring prosecution, the Examiner made a similar
`obviousness rejection of the ‘309 patent’s claims. EX1004 at 12-13. Patent Owner
`was only able to overcome the obviousness rejection by arguing the claimed
`invention had purported unexpected results. EX1004 at 24.” Pet. 44.
`Notwithstanding the “similar obviousness rejection” during prosecution and
`the Examiner’s express consideration of the US counterpart to Sofia ’634,
`Petitioner advances arguments that “Sofia ‘634 taught that the different
`diastereomers of its compounds, including compound 25, could be separated, and
`that these diastereomers would be expected to have substantially different antiviral
`activity.” Pet. 23. Petitioner further contends that “a POSA would know [from
`Sofia ’634] that the phosphorous diastereomers of any phosphoramidate nucleoside
`drug candidate must be separated and tested individually to determine which
`diastereomer provide[s] the predominant antiviral activity.” Id. at 39. According
`to Petitioner, Sofia ’634 also taught “separation of diastereomers by
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`chromatography” (id. at 41), that “[t]he compounds of Sofia ’634 were also known
`to exist as different diastereomers at phosphorous” (id. at 19), and that Example 81
`of Sofia ’634 teaches that, although “[t]he absolute stereochemistry of the P-chiral
`center of the diastereomers were not determined. . . . chromatographic resolution of
`these two diastereomers provides for isomers that are characterized as fast eluting
`and slow eluting isomers.” Id., quoting Ex. 1005, 693–694.
`Similar to its arguments regarding Sofia ’634, Petitioner contends that
`Congiatu taught separation of phosphorous diastereomers, that it would not be
`unexpected that the diastereomers would have different biological activity
`(approximately 15-fold), that the diastereomers would need to be tested to
`determine which is preferred, that mixtures of diastereomers at phosphorus are
`readily obtained and the Rp and Sp diastereomers may be separated by
`chromatography and their stereochemistry assigned. Pet. 43.
`Recognizing that Patent Owner argued unexpected results during
`prosecution, Petitioner contends that
`the claimed invention did not have unexpected results, as it would have
`been entirely expected that one of the two diastereomers would be
`highly more potent than the other. EX1002 at ¶124. As discussed
`above, a POSA would have been motivated to separate a compound
`into its diastereomers and test their separate potencies. Id. A POSA
`would also expect that one diastereomer might be much more potent
`than the other since many such examples existed, and would be highly
`motivated to perform this test. Id. Thus, Patent Owner did not show
`during prosecution of the ‘309 patent that its claims had unexpected
`results. Id.
`Pet. 44.
`We address the above factors under Section 325(d) in view of the
`prosecution history and Petitioner’s arguments.
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`Factors 1–3
`
`Sofia ’634 is the same as, or substantially similar to, the ’580 patent that the
`Examiner expressly addressed in the Notice of Allowance. Ex. 1004, 56; n.1,
`supra. Moreover, based on the Examiner’s position regarding Sofia 2007 during
`prosecution, Sofia 2007 appears to be substantially similar to Sofia ’634. See
`Ex. 1004, 12–13. Petitioner also relies on Congiatu for teachings that are
`substantially the same as Sofia ’634, such that the alleged teachings of Congiatu
`are cumulative to the alleged teachings of Sofia ’634. We thus find that the
`asserted art (Sofia ’634 and Congiatu) and the prior art involved in, and considered
`during, the examination of the ’309 patent, are the same or substantially the same.
`See Section 325(d) factors 1–3 above.
`Factor 5
`As set forth above, Petitioner’s arguments regarding separation of
`diastereomers overlap those made by Patent Owner, and addressed by the
`Examiner, during prosecution. See Section 325(d) factor 5 above.
`Factors 4 and 6
`
`Petitioner contends that the Examiner erred in determining that Patent
`Owner established unexpected results. Pet. 44. However, the citation to Exhibit
`1002, paragraph 124, in the above quoted argument regarding unexpected results is
`to a statement in the Fortunak Declaration that repeats verbatim the statements
`asserted by Petitioner, without citing evidentiary support. See Ex. 1002 ¶ 124.
`Moreover, Congiatu adds nothing to Petitioner’s argument regarding unexpected
`results as it is merely cumulative to Sofia ’634. (Compare Pet. 23: “Sofia ’634
`taught . . . that these [phosphorous] diastereomers would be expected to have
`substantially different antiviral activity” with Pet. 43: “Congiatu taught that . . . it
`would not be unexpected for there to be a very substantial . . . difference in
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`biological activity of phosphorous diastereomers.”). Therefore, Petitioner has
`neither sufficiently pointed out how the Examiner erred nor provided additional
`evidence or facts that warrant reconsideration of the Examiner’s decision. See
`Section 325(d) factors 4 and 6 above.
`
`Accordingly, pursuant to 35 U.S.C. § 325(d), we exercise our discretion and
`decline to institute on the ground of obviousness over Sofia ’634 and Congiatu.
`F. Obviousness over Clark ’147 and Congiatu
`Petitioner contends that claims 1–12 are obvious over Clark ’147 and
`Congiatu. Pet. 46–52. On this record, we determine that Petitioner has not
`established a reasonable likelihood that it would prevail in showing that any of
`claims 1–12 are obvious over Clark ’147 and Congiatu.
`Clark ’147 (Ex. 1007)
`1.
`Clark ’147 is directed to compositions and methods for treating a
`Flaviviridae infection, such as hepatitis C virus, using (2'R)-2'-deoxy-2'-fluoro-2'-
`C-methyl nucleosides. Ex. 1007, Abstract. Clark ’147 claims:
`A (2'R)-2'-deoxy-2'-fluoro-2'-C-methyl nucleoside (β-D or β-L) or its
`pharmaceutically acceptable salt or prodrug thereof of the structure:
`
`
`wherein Base is a purine or pyrimidine base; and substituents X, R1, and R7 are
`respectively one of a group of elements or compounds. Id. at 101. Clark ’147 was
`cited during the prosecution of the ’309 patent. Ex. 1001, 3.
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`
`Analysis
`2.
`Petitioner argues that “[a] POSA would have been motivated to combine the
`teachings of Clark ’147 and Congiatu because they both related to nucleoside
`phosphoramidate prodrugs.” Pet. 46. Petitioner argues that Clark ’147’s “teaching
`of diastereomers inherently taught compounds of 97–99% of the preferred
`diastereomer,” and that the recited diastereomeric purities of 97%, 98%, and 99%
`are “arbitrary limits” and “not meaningful from a standpoint of antiviral activity.”
`Id. at 49.
`Petitioner argues that Congiatu taught separation of phosphorous
`diastereomers, that it would not be unexpected that the phosphorous diastereomers
`would have different biological activity (approximately 15-fold), that the
`diastereomers must be tested to determine which is preferred as a drug candidate,
`that mixtures of diastereomers at phosphorus are readily obtained, and that the Rp
`and Sp diastereomers may be separated by chromatography and their
`stereochemistry at phosphorous assigned. Pet. 50.
`Petitioner also repeats the same argument regarding a lack of unexpected
`results that Petitioner advanced in connection with the asserted ground of
`obviousness based on Sofia ’634 and Congiatu above. Id. at 51. However,
`Petitioner cites to paragraph 142 of the Fortunak Declaration which, like the
`citation to paragraph 124 of the Fortunak Declaration in the above quote, is also to
`a statement that repeats verbatim the statements asserted by Petitioner, but without
`citation to evidentiary support. See Ex. 1002 ¶ 142.
`On this record, we are not persuaded that Petitioner has established a
`reasonable likelihood that it would prevail in showing that claim 1 would have
`been obvious over Clark ’147 and Congiatu. As an initial matter, Petitioner does
`not explain how or whether Clark ’147 discloses or even suggests the compound of
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`formula 4 (claim 1). Furthermore, Petitioner fails to establish any teaching or
`suggestion of the compound of formula 4 by Clark ’147 or Congiatu, alone or in
`combination. See CFMT, 349 F.3d at 1342; GPAC Inc., 57 F.3d at 1581.
`Moreover, other than citations to unsupported paragraphs of the Fortunak
`Declaration, Petitioner provides no persuasive explanation of how Clark ’147
`inherently teaches diastereomeric purities of 97%, 98%, and 99%. In particular,
`Petitioner fails to persuasively explain how such purities “necessarily must be
`present” in Clark ’147. See Par Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186,
`1194–96 (Fed. Cir. 2014) (discussing inherency in the obviousness context).
`Petitioner’s argument that Congiatu taught “that it would not be unexpected
`for there to be a very substantial (in this case approximately 15-fold) difference in
`biological activity of phosphorous diastereomers,” as well as its argument that “the
`claimed invention did not have unexpected results,” do not sufficiently address the
`finding of unexpected results that, according to Petitioner, was the “only” reason
`the Examiner allowed the claims of the ’309 patent. Pet. 44. Objective indicia of
`unexpected results must be considered before any conclusion regarding
`obviousness is reached, and may be the most probative evidence of
`nonobviousness. Millennium Pharms., Inc. v. Sandoz Inc., 863 F.3d 1356, 1367–
`68 (Fed. Cir. 2017) (citing cases). However, Petitioner’s arguments regarding a
`lack of unexpected results amount to little more than conclusory statements that are
`insufficient to support a conclusion of obviousness. See KSR, 550 U.S. at 418.
`Petitioner also fails to set forth any persuasive reason to combine the
`teachings of Clark ’147 and Congiatu. Instead, Petitioner supports the combination
`with a conclusory statement that relies on the same statement in the Fortunak
`Declaration that lacks citation to