Trials@uspto.gov Paper No. 11
`Tel: 571-272-7822
`Entered: July 3, 2017
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`MONOSOL RX, LLC,
`Petitioner,
`
`v.
`
`ICOS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2017-00412
`Patent 6,943,166 B1
`_______________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`Tel: 571-272-7822
`Entered: July 3, 2017
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`MONOSOL RX, LLC,
`Petitioner,
`
`v.
`
`ICOS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2017-00412
`Patent 6,943,166 B1
`_______________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`
`IPR2017-00412
`Patent 6,943,166 B1
`
`
`INTRODUCTION
`MonoSol Rx, LLC (“Petitioner”) filed a Corrected Petition (Paper 4,
`“Pet.”) to institute an inter partes review of claims 1−12 of U.S. Patent No.
`6,943,166 B1 (Ex. 1001, “the ’166 patent”). ICOS Corporation (“Patent
`Owner”) timely filed a Preliminary Response. Paper 9 (“Prelim. Resp.”).
`Based on this record, we determine Petitioner has not established a
`reasonable likelihood that it would prevail in showing the unpatentability of
`at least one challenged claim. See 35 U.S.C. § 314(a). Therefore, we deny
`institution of an inter partes review.
`Related Proceedings
`According to the parties, Patent Owner asserted the ’166 patent
`against numerous entities, but not Petitioner, in the United States District
`Court for the Eastern District of Virginia. Pet. 45; Paper 8, 2–4.
`We previously denied a petition for inter partes review of the same
`challenged claims filed by IntelGenX Corp. IntelGenX Corp. v. ICOS
`Corp., IPR2016-00678 (PTAB Sept. 1, 2016) (Paper 13). Thereafter,
`IntelGenX filed a request for rehearing, and we authorized Patent Owner to
`file a responsive brief. IPR2016-00678, Papers 14, 15. Before Patent
`Owner filed any responsive briefing, Petitioner withdrew its request.
`IPR2016-00678, Paper 16. We, thus, terminated that proceeding. IPR2016-
`00678, Paper 17.
`The ’166 patent is also the subject of IPR2017-00323, filed by Mylan
`Pharmaceuticals Inc. We instituted an inter partes review in that case.
`Mylan Pharmaceuticals Inc. v. ICOS Corp., IPR2017-00323 (PTAB June
`12, 2017) (Paper 12).
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`IPR2017-00412
`Patent 6,943,166 B1
`
`
`The ’166 Patent
`The ’166 patent relates to a highly selective phosphodiesterase (PDE)
`enzyme inhibitor, and its use in a pharmaceutical unit dosage form.
`Ex. 1001, Abstract, 1:14–16.
`Type 5 cGMP-specific PDE (PDE5) is an attractive target in the
`treatment of sexual dysfunction. Id. at 1:34–39. Before the ’166 patent
`invention, a pharmaceutical product, which provides a PDE5 inhibitor, was
`available and marketed for treating male erectile dysfunction (“ED”) under
`the trademark VIAGRA®. Id. at 1:41–43. The active ingredient in
`VIAGRA® is sildenafil. Id. at 1:43–44. According to the ’166 patent,
`however, “[w]hile sildenafil has obtained significant commercial success, it
`has fallen short due to its significant adverse side effects.” Id. at 1:58–60.
`The ’166 patent discloses a pharmaceutical unit dosage composition
`comprising about 1 to about 20 mg of compound tadalafil, which has the
`following structure:
`
`
`Id. at 3:11–28. The ’166 patent discloses that the pharmaceutical unit
`dosage is suitable for oral administration, and is useful for treating sexual
`dysfunction. Id. at 3:29–31.
`
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`IPR2017-00412
`Patent 6,943,166 B1
`
`
`Illustrative Claim
`Claim 1 is the sole independent claim challenged in the Petition. It
`reads:
`1. A method of treating sexual dysfunction in a patient in need
`thereof comprising orally administering one or more unit dose
`containing about 1 to about 20 mg, up to a maximum total dose
`of 20 mg per day, of a compound having the structure [of formula
`(I)].
`
`Asserted Grounds of Unpatentability
`Petitioner asserts the following grounds, each of which challenges the
`patentability of claims 1–12:
`Reference(s)
`Basis
`Daugan1 and the Guideline for Industry2
`§ 103
`Daugan and the FDA Petition3
`§ 103
`Daugan
` § 103
`In support of its patentability challenges, Petitioner relies on the
`Declaration of Dr. Roger Williams (Ex. 1010).
`ANALYSIS
`Claim Construction
`In an inter partes review, the Board interprets a claim term in an
`unexpired patent according to its broadest reasonable construction in light of
`the specification of the patent in which it appears. 37 C.F.R. § 42.100(b);
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016). Under
`that standard, and absent any special definitions, we assign claim terms their
`
`
`1 Daugan, WO 97/03675, published Feb. 6, 1997 (Ex. 1005).
`2 The Guideline for Industry, Dose Response Information to Support Drug
`Registration, published November 9, 1994 (Ex. 1014).
`3 Petition To Add Information About Sildenafil’s Danger’s To The Drug
`Label, Dated July 1, 1998 (Ex. 1015).
`
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`IPR2017-00412
`Patent 6,943,166 B1
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`ordinary and customary meaning, as would be understood by one of ordinary
`skill in the art at the time of the invention, in the context of the entire patent
`disclosure. 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. In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994).
`Claim terms need only be construed to the extent necessary to resolve
`the controversy. Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361
`(Fed. Cir. 2011). On this record and for purposes of this Decision, we see no
`need to construe any term expressly in order to determine whether to
`institute an inter partes proceeding.
`Prior Art Disclosures
`
`Daugan
`Daugan identifies (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-
`(3,4-methylene-dioxyphenyl)pyrazino[2',1':6.1] pyrido[3,4-b]indole-1,4-
`dione, also known as compound (A), as a compound of the invention.
`Ex. 1007, 3:24–25. Compound (A) is the same as the compound of the
`formula in the ’166 patent set forth above, i.e., tadalafil.
`Daugan teaches that tadalafil is useful for treating male or female
`sexual dysfunction. Id. at 4:25−28. According to Daugan, tadalafil may be
`administered orally to treat ED. Id. at 3:30−32. It also teaches that “for a
`typical adult patient, individual tablets or capsules contain from 0.2-400mg
`of active compound, in a suitable pharmaceutically acceptable vehicle or
`carrier, for administration in single or multiple doses, once or several times
`per day,” and that generally, the dosage is “in the range of from 0.5-800mg
`
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`IPR2017-00412
`Patent 6,943,166 B1
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`daily.” Id. at 5:1−7. Further, Daugan teaches preparing tablets with 50 mg
`active compound. Id. at 12:15−14:16.
`The Guideline for Industry
`According to the Guideline for Industry, “[d]ose response data are
`desirable for almost all new chemical entities entering the market.”
`Ex. 1014, 13. The Guideline for Industry suggests that a drug sponsor
`should use the data to
`a. Identify a reasonable starting dose, ideally with specific
`adjustments . . . .
`b. Identify reasonable, response-guided titration steps, and the
`interval at which they should be taken . . . .
`c. Identify a dose, or a response (desirable or undesirable),
`beyond which titration should not ordinarily be attempted
`because of a lack of further benefit or an unacceptable
`increase in undesirable effects.
`
`Id.
`
`The Guideline for Industry states that “[i]t is prudent to carry out
`dose-ranging or concentration-response studies early in development as well
`as in later stages in order to avoid failed Phase 3 studies or accumulation of a
`database that consists largely of exposures at ineffective or excessive doses.”
`Id.
`The FDA Petition4
`The FDA Petition appears to be a letter from Sidney M. Wolfe, M.D.,
`Larry Sasich, Pharm. D., M.P.H., and Elizabeth Barbehenn, Ph.D. to
`Michael A. Friedman, M.D., Lead Deputy Commissioner for the FDA.
`
`
`4 Patent Owner challenges the prior-art status of the FDA Petition. Prelim.
`Resp. 31–36. For purposes of this Decision, we assume, without deciding,
`that the FDA Petition qualifies as prior art under 35 U.S.C. § 102(a).
`
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`IPR2017-00412
`Patent 6,943,166 B1
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`Ex. 1015, 1, 5.
`According to the FDA Petition,
`The purposes of this letter are to petition FDA to change the
`labeling and other sources of information about Viagra to add
`important information about the drug’s dangers currently
`missing from such sources and to warn doctors and patients that
`a substantial proportion of patients using the drug are unwittingly
`using it to treat impotence or other types of sexual dysfunction
`which are probably adverse reactions caused or worsened by
`other drugs known to impair sexual function.
`Id. at 1.
`The letter states:
`There is a serious question as to whether patients, were they
`adequately informed, would choose to use sildenafil to treat the
`sexual adverse effects of another drug, especially if an alternative
`drug which did not cause sexual dysfunction or a lower dose of
`the same drug or would obviate the need for sildenafil.
`Id. at 2.
`
`Asserted Obviousness Grounds
`Petitioner contends that claims 1–12 would have been obvious over
`the teachings of Daugan, (1) alone, (2) in combination with the Guideline for
`Industry, or (3) in combination with the FDA Petition. Pet. 7–43. Based on
`the current record, we determine Petitioner has not established a reasonable
`likelihood that it would prevail on any challenged claims for any of these
`assertions.
`In all of its obviousness challenges, Petitioner refers to Daugan for
`teaching tadalafil formulations comprising individual tablets or capsules
`containing “from 0.2-400mg of active compound,” and for teaching oral
`administration of tadalafil in the “range of from 0.5-800 mg daily for an
`average adult patient.” Pet. 7, 12, 15, 27, 33, 37–38 (citing Ex. 1005, 5).
`
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`IPR2017-00412
`Patent 6,943,166 B1
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`Petitioner also refers to Daugan for stating that “[i]n practice the physician
`will determine the actual dosing regimen which will be most suitable for an
`individual patient.” Id. at 8, 15, 27, 37 (citing Ex. 1005, 5). In addition,
`Petitioner points to Daugan for providing examples of 50 mg tadalafil in oral
`dosage forms, and for teaching that “other strengths may be prepared.” Id.
`at 8, 12, 15, 27, 33, 37–38 (citing Ex. 1005, 12–16).
`Petitioner contends that these teachings of Daugan provide “a
`reasonable starting dose,” upon which an ordinary artisan “would only need
`routine optimization” to “find a maximum dose that would maintain efficacy
`and lower side effects.” Pet. 8–12, 28, 38. Citing KSR, Petitioner asserts
`that because there is a “design need or market pressure to solve a problem
`and there are a finite number of identified, predictable solutions,” an
`ordinary artisan would have found the claimed range of “about 1 to about 20
`mg, up to a maximum total dose of 20 mg per day” obvious. Id. at 9
`(quoting KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007)). In
`addition, Petitioner argues that the claimed range would have been obvious
`to try. Pet. 15, 22, 27, 38.
`Specifically, according to Petitioner, an ordinary artisan, following the
`Guideline for Industry, “could then identify reasonable, response-guided
`titration steps and the intervals at which they should be taken, with
`appropriate adjustments. Then, the [ordinary artisan] can identify a dose
`beyond which titration should not ordinarily be attempted because of a lack
`of further benefit or an unacceptable increase in undesirable effects.” Id. at
`13. In this case, Petitioner argues, an ordinary artisan would have found that
`the maximum daily dose is 20 mg. Id. at 14.
`
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`IPR2017-00412
`Patent 6,943,166 B1
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`
`Alternatively, Petitioner asserts that, in view of the FDA Petition, an
`ordinary artisan “would have known that based on the market pressure to
`compete with sildenafil, a drug manufacturer would have to market a drug
`that had the same or better efficacy, and in a dose that maintained efficacy
`but that also minimized adverse effects.” Id. at 25. Thus, according to
`Petitioner, an ordinary artisan would have been motivated to combine the
`teachings of Daugan and the FDA Petition “to use the known compound
`tadalafil, in doses that would minimize the adverse side effects, and yet
`maintain the efficacy needed to compete with sildenafil.” Id.
`We are not persuaded by Petitioner’s arguments. Petitioner may be
`correct that, in the pharmaceutical field generally, an ordinary artisan would
`strive to optimize a drug dose to minimize adverse side effects while
`maintaining efficacy. But, a claimed invention is not shown to be
`unpatentable where “the prior art gave only general guidance as to the
`particular form of the claimed invention or how to achieve it.” In re
`O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). Such is the case here.
`Daugan teaches tadalafil in a daily dose range of 0.5–800 mg and
`dosage forms with 50 mg active ingredients. The Guideline for Industry
`teaches developing dose-response information to support drug registration,
`whereas the FDA Petition merely addresses the side effects of sildenafil.
`The teachings of the asserted prior art, at best, provide “general guidance” to
`identify a maximum daily dosage of tadalafil. Petitioner does not point to
`any other persuasive evidence to account for the claimed limitation. Instead,
`Petitioner relies on “common sense.” See, e.g., Pet. 9, 21, 36. Common
`sense, however, “cannot be used as a wholesale substitute for reasoned
`analysis and evidentiary support, especially when dealing with a limitation
`
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`IPR2017-00412
`Patent 6,943,166 B1
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`missing from the prior art references specified.” Arendi S.A.R.L. v. Apple
`Inc., 832 F.3d 1355, 1362 (Fed. Cir. 2016). We, thus, are not persuaded that
`the challenged claims would have been obvious over Daugan, in
`combination with either the Guideline for Industry, or the FDA Petition.
`Petitioner further argues that the challenged claims would have been
`obvious over Daugan alone because an ordinary artisan “would be motivated
`to administer tadalafil in the claimed dose range, up to a maximum total
`dose of 20 mg per day[,] in order to obtain FDA approval.” Id. at 33. In
`support, Petitioner points to Exhibits 1018 and 1019. Id. at 34–43.
`According to Petitioner, Exhibit 1018 is “FDA Clinical Hold - 21-368
`FDA Cialis Correspondence P5.” Pet. ii. Petitioner relies on Exhibit 1018
`to support its argument that an ordinary artisan would have recognized that
`the FDA placed a clinical hold for tadalafil on December 9, 1997 for reasons
`related to dosing. Id. at 35 (citing Ex. 1010 ¶¶ 181–82 (citing Ex. 1018,
`0004)). Specifically, Petitioner argues that an ordinary artisan “would
`recognize that there was pressure to use lower doses because, ‘In fact,
`studies for tadalafil were on IND “Clinical Hold” until the sponsor agreed to
`lower the doses by upwards of 10-fold and follow patients for clinical
`evidence of arteritis.’” Id. (citing Ex. 1010 ¶¶ 181–82 (quoting Ex. 1018,
`0004)).
`According to Petitioner, Exhibit 1019 is “FDA Review – Pharmr
`Part 5.” Pet. ii. Petitioner relies on Exhibit 1019 to support its argument
`that the FDA “was aware of certain adverse effects of tadalafil during
`testing, particularly in ‘high dose groups.’” Id. at 34–35 (citing Ex. 1019).
`On its face, neither Exhibit 1018 nor Exhibit 1019 appears to be in
`existence before the priority date of the ’166 patent. Indeed, Exhibit 1018
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`IPR2017-00412
`Patent 6,943,166 B1
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`refers, in the past tense, to studies conducted in 2000 and 2001, and to
`meeting minutes dated in 2002. See, e.g., Ex. 1018, 0005, 0009, 0043, 0048.
`Similarly, Exhibit 1019 suggests that the “Review and Evaluation of
`Pharmacology/Toxicology Data” of tadalafil was completed on June 14,
`1999. Ex. 1019, 0092. The same page also shows a stamped date of “AUG
`10 1999.” Id.
`Because Petitioner has not shown either Exhibit 1018 or Exhibit 1019
`was in existence, much less publicly accessible, before April 30, 1999, the
`priority date of the ’166 patent, we are not persuaded that an ordinary artisan
`would have been motivated to modify the dosage range in Daugan to obtain
`FDA approval.
`In sum, based on the current record, we conclude Petitioner has not
`established a reasonable likelihood it would prevail in showing that any
`challenged claim would have been obvious over Daugan, (1) alone, (2) in
`combination with the Guideline for Industry, or (3) in combination with the
`FDA Petition.
`
`CONCLUSION
`On this record, Petitioner has not demonstrated a reasonable
`likelihood of prevailing on its challenges to the patentability of any
`challenged claim of the ’166 patent on the grounds asserted in the Petition.
`ORDER
`
`Accordingly, it is
`ORDERED that Petitioner’s request for an inter partes review of
`claims 1–12 of the ’166 patent is denied and no inter partes review is
`instituted.
`
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`11
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`IPR2017-00412
`Patent 6,943,166 B1
`
`PETITIONER:
`Harold Fox
`hfox@steptoe.com
`
`Gretchen Miller
`gmiller@steptoe.com
`
`PATENT OWNER:
`Mark Feldstein
`mark.feldstein@finnegan.com
`
`Joshua Goldberg
`joshua.goldberg@finnegan.com
`
`Yieyie Yang
`yieyie.yang@finnegan.com
`
`Maureen Queler
`maureen.queler@finnegan.com
`
`Mark Stewart
`stewart_mark@lilly.com
`
`Dan Wood
`wood_dan_l@lilly.com
`
`Gerald P. Keleher
`keleher_gerald@lilly.com
`
`
`12
`
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`
`
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