Trials@uspto.gov
`571-272-7822
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`Paper 12
`Entered: February 16, 2021
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`BIOCON PHARMA LIMITED,
`Petitioner,
`v.
`NOVARTIS PHARMACEUTICALS CORPORATION,
`Patent Owner.
`
`IPR2020-01263
`Patent 8,101,659 B2
`
`
`Before ERICA A. FRANKLIN, ROBERT A. POLLOCK, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`SAWERT, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. §§ 314, 325(d)
`
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`
`
`571-272-7822
`
`Paper 12
`Entered: February 16, 2021
`
`
`
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`BIOCON PHARMA LIMITED,
`Petitioner,
`v.
`NOVARTIS PHARMACEUTICALS CORPORATION,
`Patent Owner.
`
`IPR2020-01263
`Patent 8,101,659 B2
`
`
`Before ERICA A. FRANKLIN, ROBERT A. POLLOCK, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`SAWERT, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. §§ 314, 325(d)
`
`
`
`
`
`
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`
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`IPR2020-01263
`Patent 8,101,659 B2
`
`INTRODUCTION
`I.
`Biocon Pharma Limited (“Petitioner”) filed a Petition (Paper 1,
`“Pet.”) requesting inter partes review of claims 1–4 of U.S. Patent
`No. 8,101,659 B2 (Ex. 1001, “the ’659 patent”) pursuant to 35 U.S.C. § 311.
`Novartis Pharmaceuticals Corporation (“Patent Owner”) timely filed a
`Preliminary Response (Paper 7, “Prelim. Resp.”). On our authorization
`(Paper 9, “Order”), Petitioner filed a preliminary Reply (Paper 10, “Reply”)
`and Patent Owner filed a preliminary Sur-Reply (Paper 11, “Sur-Reply”).
`We have the authority and discretion to determine whether to institute
`an inter partes review. 35 U.S.C. § 314; 37 C.F.R. § 42.4. We may not
`institute an inter partes review “unless . . . there is 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). After considering the
`Petition, Preliminary Response, Reply, and Sur-Reply, as well as the
`associated evidence, we exercise our discretion to deny institution of inter
`partes review under 35 U.S.C. §325(d).
`II. BACKGROUND
`A. Real Parties-In-Interest
`Petitioner identifies Biocon Limited, Biocon Pharma Limited, and
`Biocon Pharma, Inc. as the real parties-in-interest. Pet. 70. Patent Owner
`identifies Novartis Pharmaceuticals Corporation as the real party-in-interest.
`Paper 6, 1.
`
`B. Related Matters
`Petitioner and Patent Owner state the ’659 patent has been, or is, at
`issue in several judicial proceedings. Pet. 7–9; Paper 6, 1. Patent Owner
`specifically identifies the following judicial proceedings as related matters:
`(1) In Re: Entresto (Sacubitril/Valsartan) Patent Litig., No. 20-md-2930-
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`Patent 8,101,659 B2
`LPS; (2) Novartis Pharm. Corp. v. Alkem Labs. Ltd., No. 19-cv-1979-LPS
`(D. Del.); (3) Novartis Pharm. Corp. v. Alembic Pharm. Ltd., No. 19-cv-
`2021-LPS (D. Del.); (4) Novartis Pharm. Corp. v. Dr. Reddy’s Labs., Inc.,
`No. 19-cv-2053-LPS (D. Del.); (5) Novartis Pharm. Corp. v. Alembic
`Pharm. Ltd., No. 20-cv-74-LPS (D. Del.); (6) Novartis Pharm. Corp. v.
`Lupin Atlantis Holdings, S.A., No. 20-cv-415-LPS (D. Del.); (7) Novartis
`Pharm. Corp. v. Mylan Pharm. Inc., No. 20-cv-445-LPS (D. Del.);
`(8) Novartis Pharm. Corp. v. Mylan Pharm. Inc., No. 19-cv-201-IMK (N.D.
`W.Va.); and (9) Novartis Pharm. Corp. v. Macleods Pharm. Ltd., No. 19-cv-
`19345 (D.N.J.) (dismissed). Paper 6, 1.
`C. The ’659 Patent (Ex. 1001)
`The ’659 patent, titled “Methods of Treatment and Pharmaceutical
`Composition,” issued January 24, 2012, based on an application filed June
`27, 2008. Ex. 1001, codes (22), (45), (54). The ’659 patent relates to a
`pharmaceutical composition comprising valsartan and an NEP inhibitor,
`namely, N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-
`2R-methylbutanoic acid ethyl ester (“sacubitril”) or (2R,4S)-5-biphenyl-4-
`yl-4(3-carboxy-propionyl amino)-2-methyl-pentanoic acid. Id. at 3:19–22,
`16:16–25. Valsartan is an AT 1-receptor antagonist. According to the ’659
`patent, AT 1-receptor antagonists “can be used, e.g., as anti-hypertensive’s
`[sic] or for the treatment of congestive heart failure, among other
`conditions.” Id. at 1:49–51. NEP inhibitors “lower blood pressure and exert
`ANF-like effects, such as diuresis and increased cyclic guanosine 3′,5′-
`monophosphate (cGMP) excretion.” Id. at 2:39–43.1
`
`1 The written description of the ’659 patent explains that ANFs (atrial
`natriuretic factors), “also known as ANPs, brain natriuretic peptide (BNP),
`met and leu enkephalin, bradykinin, neurokinin A and substance P . . . . are a
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`Patent 8,101,659 B2
`The ’659 patent states that “combination therapy with valsartan and a
`NEP inhibitor results in a more effective anti-hypertensive therapy . . .
`through improved efficacy, as well as a greater responder rate.” Id. at 6:65–
`7:3. In particular, the ’659 patent states that “[i]t has surprisingly been
`found that, a combination of valsartan and a NEP inhibitor achieves greater
`therapeutic effect than the administration of valsartan, ACE inhibitors or
`NEP inhibitors alone and promotes less angioedema than is seen with the
`administration of a vasopeptidase inhibitor alone.” Id. at 6:41–45. The ’659
`patent states that the combination therapy “is also useful in the treatment or
`prevention of heart failure.” Id. at 7:3–4.
`D. Illustrative Claim
`Of the challenged claims, claim 1 is independent. Ex. 1001, 16:16–
`33. Claims 2–4 depend, directly or indirectly, from claim 1. Id. at 16:34–
`47. Claim 1, reproduced below, illustrates the claimed subject matter:
`1.
` A pharmaceutical composition comprising:
`(i) the AT 1-antagonist valsartan or a pharmaceutically
`acceptable salt thereof;
`the NEP
`inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-
`phenylphenylmethyl)-4-amino-2R-methylbutanoic
`acid
`ethyl ester or
`(2R,4S)-5-biphenyl-4-yl-4(3-carboxy-
`propionyl
`amino)-2-methyl-pentanoic
`acid
`or
`a
`pharmaceutically acceptable salt thereof, and
`(iii) a pharmaceutically acceptable carrier;
`wherein said (i) AT 1-antagonist valsartan or pharmaceutically
`acceptable salt thereof and said (ii) NEP inhibitor N-(3-
`carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-
`amino-2R-methylbutanoic acid ethyl ester or (2R,4S)-5-
`
`family of vasodilator, diuretic and anti-hypertensive peptides,” and among
`the substrates for the zinc-metalloprotease, NEP (neutral endopeptidase). Id.
`at 2:10–21.
`
`(ii)
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`Patent 8,101,659 B2
`biphenyl-4-yl-4(3-carboxy-propionylamino)-2-methyl-
`pentanoic acid or pharmaceutically acceptable salt thereof,
`are administered in combination in about a 1:1 ratio.
`Id. at 16:16–33.
`
`E. Asserted Evidence
`Petitioner submits the following evidence:
`Evidence
`EP 0 726 072 A2 (published Aug. 14, 1996) (“EP ’072”)
`Shetty and DelGrande, Differential Inhibition of the
`Prejunctional Actions of Angiotensin II in Rat Atria by
`Valsartan, Irbesartan, Eprosartan, and Losartan, J.
`PHARMACOL. EXP. THER. 294:179–186 (2000) (“Shetty”)
`Gomez-Monterrey et al., New Thiol Inhibitors of Neutral
`Endopeptidase EC 3.4.24.11: Synthesis and Enzyme
`Active-Site Recognition, J. MED. CHEM. 37:1865–1873
`(1994) (“Gomez-Monterrey”)
`Ksander et al., Dicarboxylic Acid Dipeptide Neutral
`Endopeptidase Inhibitors, J. MED. CHEM. 38:1689–1700
`(1995) (“Ksander”)
`U.S. Pat. No. 5,217,996 (issued June 8, 1993) (“the ’996
`patent”)
`Physicians’ Desk Reference, Edition 54 (2000) (“PDR”).
`Declaration of Y.W. Francis Lam, Pharm.D.
`
`Exhibit No.
`1002
`
`1004
`
`1005
`
`1006
`
`1009
`1012
`1018
`
`F. Asserted Grounds of Unpatentability
`Petitioner asserts that claims 1–4 are unpatentable under 35 U.S.C.
`
`§ 103(a)2 based on the following grounds:
`
`
`2 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125
`Stat. 284 (2011) (“AIA”), amended several provisions of 35 U.S.C.,
`including § 103. Because the ’659 patent claims priority to an application
`that has an effective filing date prior to the effective date of the applicable
`AIA amendments, we refer herein to the pre-AIA version of § 103.
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`IPR2020-01263
`Patent 8,101,659 B2
`Claims Challenged
`1–4
`
`1–4
`
`Pet. 14.
`
`35 U.S.C. §
`103(a)
`
`103(a)
`
`References/Basis
`EP ’072, Shetty, Gomez-
`Monterrey, Ksander
`PDR, the ’996 patent, Gomez-
`Monterrey, EP ’072
`
`III. DISCRETION UNDER 35 U.S.C. § 325(d)
`Section 325(d) provides that the Director may elect not to institute a
`proceeding if the challenge to the patent is based on matters previously
`presented to the Office. Advanced Bionics, LLC v. Med-El
`Elektromedizinische Geräte GmbH, IPR2019-01469, Paper 6 at 7 (PTAB
`Feb. 13, 2020) (precedential) (“Advanced Bionics”).3 In evaluating matters
`under § 325(d), the Board uses the following two-part framework:
`(1) determining whether the same or substantially the same art previously
`was presented to the Office or whether the same or substantially the same
`arguments previously were presented to the Office; and (2) if either
`condition of the first part of the framework is satisfied, determining whether
`the petitioner has demonstrated that the Office erred in a manner material to
`the patentability of challenged claims. Id. at 8.
`We consider several non-exclusive factors as set forth in Becton,
`Dickinson & Co. v. B. Braun Melsungen AG, IPR2017-01586, Paper 8
`(Dec. 15, 2017) (precedential as to § III.C.5, first paragraph) (“Becton,
`Dickinson”), which “provide useful insight into how to apply the
`framework” under § 325(d). Advanced Bionics, 9. These non-exclusive
`factors include:
`
`
`3 The Board institutes trial on behalf of the Director. 37 C.F.R.
`§ 42.4(a); Advanced Bionics, 7 n.7.
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`IPR2020-01263
`Patent 8,101,659 B2
`(a) the similarities and material differences between the asserted
`art and the prior art involved during examination;
`(b) the cumulative nature of the asserted art and the prior art
`evaluated during examination;
`(c) the extent to which the asserted art was evaluated during
`examination, including whether the prior art was the basis for
`rejection;
`(d) the extent of the overlap between the arguments made during
`examination and the manner in which Petitioner relies on the
`prior art or Patent Owner distinguishes the prior art;
`(e) whether Petitioner has pointed out sufficiently how the
`Examiner erred in its evaluation of the asserted prior art; and
`(f) the extent to which additional evidence and facts presented in
`the Petition warrant reconsideration of the prior art or arguments.
`Becton, Dickinson, 17–18 (formatting added). “If, after review of factors
`(a), (b), and (d), it is determined that the same or substantially the same art
`or arguments previously were presented to the Office, then factors (c), (e),
`and (f) relate to whether the petitioner has demonstrated a material error by
`the Office.” Advanced Bionics, 10.
`Patent Owner argues that we should exercise our discretion under
`§ 325(d) and deny institution. Prelim. Resp. 22–38; Sur-Reply 1–3.
`Petitioner opposes. Pet. 64–67; Reply 1–3. Upon consideration of the
`parties’ respective arguments, discussed in detail below, and the relevant
`Becton, Dickinson factors as applied to the record in this case, we find that
`the factors weigh in favor of exercising our discretion under § 325(d). Thus,
`pursuant to the Board’s precedent set forth in Advanced Bionics, we deny
`institution of the Petition for inter partes review.
`A. Becton, Dickinson Factors (a), (b), and (d)
`Becton, Dickinson factors (a), (b), and (d) relate to whether the same
`or substantially the same art or arguments were presented previously to the
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`Patent 8,101,659 B2
`Office. Advanced Bionics, 10. Petitioner contends that “[t]he Examiner
`never put forth any rejection as outlined in this Petition.” Pet. 64. As noted
`above, Petitioner’s grounds of unpatentability rely on prior-art references
`EP ’072, Shetty, Gomez-Monterrey, and Ksander in the first ground, and
`PDR, the ’996 patent, Gomez-Monterrey, and EP ’072 in the second ground.
`Pet. 14. Petitioner contends that prior-art references PDR, Shetty, Gomez-
`Monterrey, and Ksander were not before the Examiner during prosecution.
`Id. Petitioner acknowledges that the remaining prior-art references (i.e.,
`EP ’072 and the ’996 patent) were disclosed to the Examiner during
`prosecution of the application leading to the ’659 patent, but contends that
`the Board “has consistently declined to exercise its discretion under § 325(d)
`based on the mere citation of references in an [Information Disclosure
`Statement (IDS)] that were not applied by the Examiner.” Id. at 64 (quoting
`Apotex, Inc. v. UCB Biopharma, SPRL, IPR2019-00400, Paper 17 at 24
`(PTAB July 15, 2019)). Petitioner also contends that its grounds of
`unpatentability set forth “specific arguments and rationales” that were not
`before the Examiner. Reply 1.
`Patent Owner, in contrast, argues that “[t]he Examiner considered
`substantially the same art and/or arguments during prosecution.” Prelim.
`Resp. 23. Patent Owner argues that EP ’072 and the ’996 patent were before
`the Examiner during prosecution, and that the Petition’s remaining prior-art
`references (i.e., PDR, Shetty, Gomez-Monterrey, and Ksander) are merely
`cumulative to the prior-art references the Examiner applied during
`prosecution. Id. at 23–25; Sur-Reply 1. Patent Owner also argues that
`Petitioner’s grounds of unpatentability are based on the same arguments that
`led the Examiner to twice reject the claims of the application leading to the
`’659 patent for prima facie obviousness. Prelim. Resp. 23–25.
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`Patent 8,101,659 B2
`Upon consideration of the parties’ respective arguments and the
`prosecution history of the ’659 patent, we find that Patent Owner has the
`better position. In particular, we agree with Patent Owner that the Petition
`advances the same or substantially the same art that was presented
`previously to the Office.4
`Both EP ’072 and the ’996 patent were presented previously to the
`Office during prosecution. The record shows that the Examiner signed an
`IDS listing both EP ’072 and the ’996 patent. Ex. 1010, 89–90. The IDS
`also states that the Examiner considered both prior-art references. Id. In
`light of the Board’s precedential Advanced Bionics decision, we reject
`Petitioner’s contention that, even though EP ’072 appears on an IDS, we
`should decline to exercise discretion under § 325(d) because EP ’072 was
`“not applied by the Examiner.” Pet. 64. As explained in Advanced Bionics,
`“[p]reviously presented art includes art made of record . . . such as on an
`Information Disclosure Statement (IDS).” Advanced Bionics, 7–8. Thus,
`we accept that the Examiner considered EP ’072 because it is listed on the
`IDS and the Examiner signed the IDS with the statement “all references
`considered except where lined through.” Ex. 1010, 90.
`Turning to the remaining prior-art references that constitute
`Petitioner’s grounds of unpatentability (i.e., PDR, Shetty, Gomez-
`Monterrey, and Ksander), we agree with Patent Owner that these references
`are cumulative, and thus substantially similar, to the art presented previously
`
`
`4 Because we determine that the “same or substantially the same prior
`art” was presented previously to the Office, we need not reach whether the
`“same or substantially the same arguments” were presented previously to the
`Office. Advanced Bionics, 20.
`
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`Patent 8,101,659 B2
`to the Office. During prosecution, the Examiner relied on U.S. Patent
`No. 5,339,578 (“the ’578 patent,” Ex. 1008) for teaching the AT 1-
`antagonist valsartan as an anti-hypertensive treatment, and on the ’996
`patent for teaching the NEP inhibitor sacubitril as an anti-hypertensive
`treatment. See, e.g., Ex. 1010, 84–85. The Examiner determined that
`“employ[ing] combinations of a specific NEP inhibitor and valsartan would
`have been obvious because all the components are well known individually
`for treating hypertension.” Id. at 85.
`In its first ground of unpatentability, Petitioner relies on EP ’072 for
`teaching a combination of AT 1-antagonist irbesartan and NEP inhibitor
`SQ 28603. Pet. 1–2. Petitioner relies on Shetty for teaching the
`effectiveness of valsartan as an AT 1-antagonist, id. at 2, 20–22, 29, on
`Ksander for teaching the effectiveness of sacubitril (i.e., “compound 19a”)
`as an NEP inhibitor, id. at 3–4, 32–36, and on Gomez-Monterrey for
`teaching the relative ineffectiveness of SQ 28603, id. at 3, 31–32. Put
`differently, Petitioner begins with the teachings of EP ’072, already before
`the Office, and relies on Shetty to substitute the claimed valsartan for
`EP ’072’s irbesartan and on Ksander and Gomez-Monterrey to substitute the
`claimed sacubitril for EP ’072’s SQ 28603. Id. at 1–3. In its second ground
`of unpatentability, Petitioner relies on PDR for teaching valsartan as a
`specific AT 1-antagonist. Id. at 26, 46.
`The use of valsartan as an AT 1-antagonist, however, was already
`provided in the teachings of the ’578 patent and the use of sacubitril as a
`NEP inhibitor was disclosed in the ’996 patent. Ex. 1010, 84–85, 170–172,
`195–197. EP ’072— teaching the combination of an AT 1-antagonist and an
`NEP inhibitor—was also presented previously to the Office. Thus, we agree
`with Patent Owner that PDR, Shetty, Gomez-Monterrey, and Ksander do not
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`Patent 8,101,659 B2
`provide any additional information relevant to the claim limitations at issue
`that was not already presented to, and considered by, the Office. Sur-Reply
`1. For these reasons, we determine that the Petition presents the same or
`substantially the same art previously presented to the Office. Advanced
`Bionics, 10.
`
`B. Becton, Dickinson Factors (c), (e), and (f)
`Because the first part of the Advanced Bionics two-part framework is
`satisfied, we now turn to Becton, Dickinson factors (c), (e), and (f)—that is,
`“whether the petitioner has demonstrated that the Office erred in a manner
`material to the patentability of [the] challenged claims.” Advanced Bionics,
`8. According to Advanced Bionics, for the second part of the two-part
`framework, “[i]f . . . the petitioner fails to make a showing of material error,
`the Director generally will exercise discretion not to institute inter partes
`review.” Advanced Bionics, 8–9.
`Petitioner contends that “the Examiner overlooked the specific
`teaching of EP ’072 causing material error.” Pet. 65. In particular,
`Petitioner contends that, during prosecution, the Examiner allowed the
`claims of the ’659 patent only upon a showing of experimental data in the
`Webb Declaration5 of a synergistic effect from the combination of valsartan
`and a specific NEP inhibitor. Id. at 66. Petitioner highlights the Examiner’s
`statement in the Reasons for Allowance that “the experimental data showing
`that the combination of valsartan and the specific NEP inhibitor (AH377)
`has a synergistic, unexpected and surprising antihypertensive effect . . . is
`not taught or obvious from the prior art.” Id. (quoting Ex. 1010, 240). “Had
`
`
`5 See Declaration under 37 C.F.R. § 1.132 (“the Webb Declaration”).
`Ex. 1015, 884–919.
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`Patent 8,101,659 B2
`the Examiner reviewed EP ’072,” Petitioner contends, “the Examiner would
`have noted that the alleged unexpected results reported in the Webb
`Declaration of the ’659 patent are the exact same results taught by EP ’072.”
`Id.
`
`In this respect, Petitioner contends that EP ’072 “teaches that a
`combination of an AT 1-antagonist (i.e., irbesartan) and a NEP inhibitor
`(i.e., SQ 28603) produced synergistic effects, i.e., significant reductions in
`both Left Ventricular End Diastolic Pressure (LVEDP) and Left Ventricular
`Systolic Pressure (LVSP) that were greater than those produced by either
`treatment alone.” Pet. 61 (citing Ex. 1002, 2:29–31, 9:22–23). Petitioner
`also contends that “EP ’072 even expressly refers to the effect of the
`addition of these two active classes as acting ‘synergistically.’” Id. at 61
`(quoting Ex. 1002, 2:27; citing Ex. 1008 ¶ 232). “Since the Examiner was
`convinced that the alleged synergistic effect” shown in the Webb
`Declaration was “‘not taught or obvious from the cited prior art,’” Petitioner
`contends, “the only reasonable conclusion is the Examiner overlooked the
`specific teaching of EP ’072 causing a material error.” Id. at 65 (quoting
`Ex. 1010, 240).
`Patent Owner argues that Petitioner “has not met its burden of
`showing the Office erred in a manner material to patentability in concluding
`the Webb Declaration synergistic antihypertensive results were unexpected
`over the prior art.” PO Resp. 27. Patent Owner argues that Petitioner’s
`reliance on Example 1(b) of EP ’072 for a showing of synergy from the
`combination of an AT 1-antagonist and a NEP inhibitor is inapt because that
`example is not “directed to hypertension.” Id. at 28. Instead, Patent Owner
`argues, EP ’072’s Example 2 shows “failed hypertension results [that]
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`Patent 8,101,659 B2
`further confirm the unexpectedness of the Webb Declaration data.” Id. at
`32.
`
`Upon consideration of the parties’ respective arguments and the
`prosecution history of the ’659 patent, we again find that Patent Owner has
`the better position. As Patent Owner explains, EP ’072 provides two
`examples testing the cardiovascular effects of a combination AT 1-
`antagonist and a NEP inhibitor that are relevant here: Example 1(b),
`describing the cardiovascular effect of BMS 186295 (i.e., irbesartan) and SQ
`28603 (a NEP inhibitor) in “cardiomyopathic hamsters,” Ex. 1002, 7:28–31,
`and Example 2, describing the cardiovascular effect of BMS 186295 and SQ
`28603 “in dogs that had been rendered hypertensive by prior unilateral
`nephrectomy and construction of the remaining renal artery,” id. at 9:31–32.
`In Example 1(b), EP ’072 teaches that the combination of BMS 186295 and
`SQ 28603 produced synergistic “hemodynamic effects in cardiomyopathic
`hamsters in compensated heart failure”:
`The combination of BMS 186295 and SQ 28603 produced
`cardiovascular effects that were greater than those with either
`treatment alone. Specifically, the combination caused significant
`decreases in left ventricular end diastolic pressure [LVEDP] and
`left ventricular systolic pressure [LVSP] with no significant
`change in heart rate.
`Id. at 9:22–27. But, in Example 2, EP ’072 teaches that, while BMS 186295
`alone “reduced mean arterial pressure (MAP)” in hypertensive dogs, “[t]he
`effects of the combination BMS 186295 and SQ 28603 were not consistently
`different from those of [placebo].” Id. at 10:33–35.
`The record supports Patent Owner’s argument that Example 1(b) of
`EP ’072 does not relate to hypertension, and thus, fails to show material
`error in the Examiner’s consideration of the Webb Declaration. Prelim.
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`Patent 8,101,659 B2
`Resp. 28–31. As noted above, the Examiner allowed the claims of the ’659
`patent upon the showing of synergistic experimental results in the Webb
`Declaration. See Ex. 1010, 240 (Reasons for Allowance). The Webb
`Declaration provides experimental data that “the pharmaceutical
`combination of [sacubitril] and valsartan as claimed . . . has (i) synergy in
`lowering mean arterial pressure in animal models of hypertension as
`compared to monotherapy with either active agent alone.” Ex. 1015, 885
`¶ 5. The Webb Declaration further states that “this synergy is an unexpected
`and surprising blood pressure lowering effect which would not be expected
`by one of ordinarily skill in the art.” Id.
`Although Petitioner relies on Example 1(b) of EP ’072 for “expressly
`[teaching] the same synergistic effect when combining an AT 1-antagonist
`with a NEP inhibitor,” Pet. 5 (emphasis added), we agree with Patent Owner
`that EP ’072’s synergistic effect is not, in fact, the same synergistic effect as
`that shown in the Webb Declaration. Specifically, EP ’072 supports Patent
`Owner’s argument that the cardiomyopathic hamsters utilized in Example
`1(b) had low blood pressure and elevated levels of atrial natriuretic peptide
`(ANP), and thus, were a model for heart failure rather than hypertension.
`See Ex. 1002, 6:39–43 (teaching that cardiomyopathic hamsters are
`characterized (as compared with control hamsters) by low mean arterial
`pressure” and “an 8–10-fold increase in plasma natriuretic peptide
`concentration”); see also Prelim. Resp. 29. With respect to high ANP levels
`specifically, other record evidence supports Patent Owner’s argument that
`EP 072’s cardiomyopathic hamsters are a model of heart failure. See
`Ex. 2003, Abstract (teaching that “[a]n elevated plasma concentration of
`atrial natriuretic peptide (ANP) is characteristic of congestive heart failure
`
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`IPR2020-01263
`Patent 8,101,659 B2
`(CHF) in both humans and animals”).6 The elevated level of ANP in the
`cardiomyopathic hamsters contrasts with the “normal plasma
`concentrations” of ANP in the hypertensive dogs utilized in EP ’072’s
`Example 2.
`In its Reply, Petitioner does not refute Patent Owner’s argument that
`EP ’072’s Example 1(b) does not relate to hypertension. See generally
`Reply 2–3. Instead, Petitioner contends that, to the extent the Webb
`Declaration’s “alleged unexpected results are only limited to an
`antihypertensive effect,” these results “are not commensurate with the scope
`of the [’659 patent’s] claims.” Id. Petitioner points out that, of the ’659
`patent’s four claims, claims 1, 3, and 4 “are not limited to any specific
`condition, whereas [c]laim 2 recites hypertension or heart failure.” Id.
`Although we have considered Petitioner’s contentions, we are not
`persuaded that they show material error by the Examiner. Claims 1–4 of the
`’659 patent are composition claims. Reply 2; see also Ex. 1001, 16:17–47
`(claims 1–4 directed to a “pharmaceutical composition”). As Patent Owner
`argues, and we agree, “[f]or such claims, showing unexpected superiority for
`one property is sufficient to overcome a prima facie showing of
`obviousness.” Reply 2 (citing In re Chupp, 816 F.2d 643, 646 (Fed. Cir.
`1987) (“Evidence that a compound is unexpectedly superior in one of a
`spectrum of common properties, as here, can be enough to rebut a prima
`facie case of obviousness.”)). Here, the Examiner relied on unexpected
`synergistic results of an anti-hypertensive effect to allow the claims.
`Petitioner fails to show persuasively that the Examiner’s reliance on those
`
`6 Smits, et al., Effect of Endopeptidase 24.11 Inhibition in Conscious
`Cardiomyopathic Hamsters, 254(1) J. PHARMACOL. EXP. THER. 176–179
`(1990).
`
`15
`
`
`
`IPR2020-01263
`Patent 8,101,659 B2
`synergistic results for one property (i.e., anti-hypertensive effect) within the
`scope of the claims constitutes a material error under Advanced Bionics.
`Indeed, as the Federal Circuit has explained, “[o]bjective evidence of
`nonobviousness need only be reasonably commensurate with the scope of
`the claims, and we do not require a patentee to produce objective evidence
`of nonobviousness for every potential embodiment of the claim.” Rambus
`Inc. v. Rea, 731 F.3d 1248, 1257 (Fed. Cir. 2013); see also id.
`(characterizing the Board’s finding that patentee’s evidence relating to high-
`speed memory systems was not commensurate with the scope of the claims
`because the claims did not recite a specific clock speed and therefore
`embraced slow memory devices as unduly “strict” and “improper”).7
`We are also persuaded by Patent Owner’s argument that EP ’072’s
`Example 2 supports the Examiner’s finding that the Webb Declaration’s
`showing of synergistic anti-hypertensive effect from the combination of a
`NEP inhibitor and valsartan was unexpected over the prior art. Prelim.
`Resp. 32–35. Example 2 of EP ’072 shows that, in a 1K1C dog model of
`hypertension, “[t]he effects of the combination BMS 186295 and SQ 28603
`were not consistently different from those of [placebo].” Ex. 1002, 10:33–
`35. This contrasts with the Webb Declaration’s showing that the
`combination of valsartan and sacubitril had an anti-hypertensive effect that
`was greater than the sum of the effect of valsartan alone plus that of
`sacubitril alone. Compare Ex. 1002, 10:33–35, with Ex. 1015, 891 ¶ 16.
`Petitioner does not address, or otherwise refute, Patent Owner’s
`
`
`7 Petitioner also appears to suggest that Patent Owner misled the
`Examiner as to the full scope of the claims and/or the Webb Declaration.
`See Reply 2–3. These contentions are outside our jurisdiction and, thus, we
`do not consider them. 35 U.S.C. § 311(b).
`
`16
`
`
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`IPR2020-01263
`Patent 8,101,659 B2
`characterization of the results of Example 2. See generally Reply. For these
`reasons, we find no material error in the Examiner’s finding that the anti-
`hypertensive effect shown in the Webb Declaration was “not taught or
`obvious from the cited prior art.” Ex. 1010, 240.
`Petitioner also contends that we should not give weight to the
`Examiner’s findings of synergism because the Webb Declaration fails to
`compare its “allegations of unexpected results . . . to the closest prior art,”
`and because, “at best this improvement would be an improvement in degree,
`not in kind, and therefore . . . not probative of obviousness.” Pet. 62 (citing
`Ex. 1018 ¶¶ 235–236). We are not persuaded. As to the former, we find
`that EP ’072 does not support Petitioner’s contention that “the combination
`of it AT 1-antagonist and a NEP inhibitor provides the same improvements
`over the monotherapy as alleged by Patent Owner to the Examiner” for the
`reasons explained immediately above. Id. As to the latter, we find that
`Petitioner does not provide persuasive evidence sufficient to support its
`contention that, in view of EP ’072, the Webb Declaration shows only “an
`improvement in degree, not in kind, and therefore the alleged unexpected
`results are not probative of obviousness.” Id. Although Petitioner cites to
`Dr. Lam’s Declaration, Dr. Lam simply repeats Petitioner’s argument
`without providing any underlying data. See Ex. 1018 ¶ 236. We also
`observe that Petitioner does not otherwise contend that the data presented in
`the Webb Declaration is inaccurate. See PO Resp. 29 (“[Petitioner] does not
`challenge that the Webb Declaration reported synergistic antihypertensive
`results”); see also generally Pet., Reply.
`Finally, Petitioner contends that “relying on uncontested testimonial
`evidence from prosecution will not defeat an inter partes review for
`purposes of institution,” and that “the Examiner did not have the benefit of
`
`17
`
`
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`IPR2020-01263
`Patent 8,101,659 B2
`expert declaration of Dr. Lam explaining the art from the perspective of a
`[person having ordinary skill in the art].” Pet. 65–66; see also Reply 3
`(stating that “the PTAB routinely defers detailed consideration of any
`objective indicia until after institution”). Although arguably relevant to
`Becton, Dickinson factor (f), we determine that neither of these contentions,
`even if true, outweigh Petitioner’s failure in this proceeding to show material
`error in the Examiner’s consideration of the Webb Declaration, as Advanced
`Bionics requires.
`
`C. Summary
`For the reasons discussed above, we exercise our discretion under 35
`U.S.C. § 325(d) to deny institution of trial. As required by Advanced
`Bionics, we determine that the same or substantially the same art previously
`was presented to the Office and that Petitioner has not demonstrated that the
`Examiner erred when considering the prior art.
`IV. CONCLUSION
`For the foregoing reasons, we exercise our discretion to deny
`institution of inter partes review under 35 U.S.C. § 325(d).
`V. ORDER
`After due consideration of the record before us, and for the foregoing
`reasons, it is:
`ORDERED that the Petition is denied as to all challenged claims, and
`no trial is instituted.
`
`18
`
`
`
`IPR2020-01263
`Patent 8,101,659 B2
`FOR PETITIONER:
`
`Christopher Ferenc
`Brian Sodikoff
`KATTEN MUCHIN ROSENMAN LLP
`christopher.ferenc@kattenlaw.com
`brian.sodikoff@kattenlaw.com
`
`
`FOR PATENT OWNER:
`
`Nicholas N. Kallas
`Christina Schwarz
`VENABLE LLP
`nkallas@Venable.com
`cschwarz@venable.com
`
`
`19
`
`
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