Trials@uspto.gov
`Tel: 571-272-7822
`
`
`Paper 12
`Entered: June 12, 2017
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`ICOS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2017-00323
`Patent 6,943,166 B1
`_______________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`Tel: 571-272-7822
`
`
`Paper 12
`Entered: June 12, 2017
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`ICOS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2017-00323
`Patent 6,943,166 B1
`_______________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
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`IPR2017-00323
`Patent 6,943,166 B1
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`INTRODUCTION
`Mylan Pharmaceuticals Inc. (“Petitioner”) filed a Petition (Paper 2,
`“Pet.”) to institute an inter partes review of claims 112 of U.S. Patent No.
`6,943,166 B1 (Ex. 1001, “the ’166 patent”). ICOS Corporation (“Patent
`Owner”) filed a Preliminary Response. Paper 9 (“Prelim. Resp.”). We
`review the Petition under 35 U.S.C. § 314.
`For the reasons provided below, we determine Petitioner has satisfied
`the threshold requirement set forth in 35 U.S.C. § 314(a). Because
`Petitioner has established a reasonable likelihood that it would prevail in
`showing the unpatentability of at least one challenged claim, we institute an
`inter partes review of claims 1–12.
`Related Proceedings
`According to the parties, Patent Owner asserted the ’166 patent
`against Petitioner in Eli Lilly and Company et al. v. Mylan Pharmaceuticals
`Inc., No. 1:16-cv-01122 (E.D. Va.). Pet. 25; Paper 8, 2. Patent Owner also
`asserted the ’166 patent against numerous other entities in the same district
`court. Pet. 25–26; 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.
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`Patent 6,943,166 B1
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`
`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. The ’166 patent
`acknowledges a prior-art 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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`Patent 6,943,166 B1
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`
`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 Ground of Unpatentability
`Petitioner challenges the patentability of claims 1–12 based on a
`single ground—obviousness over the combination of Daugan,1 SNDA,2 and
`the FDA Guideline.3
`In support of its patentability challenges, Petitioner relies on the
`Declaration of Drs. George Grass (Ex. 1002) and Muta M. Issa (Ex. 1004).
`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
`ordinary and customary meaning, as would be understood by one of ordinary
`
`
`1 Daugan, International Publication No. WO 97/03675, published Feb. 6,
`1997 (Ex. 1007, “Daugan”).
`2 Center for Drug Evaluation and Research, Approval Package for
`VIAGRA®, Approval Date March 27, 1998 (Ex. 1008, “SNDA”).
`3 Dose-Response Information to Support Drug Registration, 59 Fed. Reg.
`55972 (Nov. 9, 1994) (Ex. 1009, “the FDA Guideline”).
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`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.
`Disclosures of Asserted Prior Art
`
`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 4:2528. According to Daugan, tadalafil may be
`administered orally to treat ED. Id. at 3:3032. 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
`daily.” Id. at 5:17. Further, Daugan teaches preparing tablets with 50 mg
`active compound. Id. at 12:1514:16.
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`SNDA
`SNDA teaches sildenafil is a potent PDE5 inhibitor and is useful for
`treating ED. Ex. 1008, 35. Sildenafil is therapeutically effective for treating
`ED at doses of 25, 50, and 100 mg. Id. at 127–28, 215, 217–19. According
`to SNDA, in some patients, doses as low as 5 and 10 mg are therapeutically
`effective over placebo. Id. SNDA states that the “maximum recommended
`dosing frequency is once per day.” Id. at 50.
`The FDA Guideline
`The FDA guideline “describes why dose-response information is
`useful and how it should be obtained in the course of drug development.
`This information can help identify an appropriate starting dose as well as
`how to adjust dosage to the needs of a particular patient. It can also identify
`the maximum dosage beyond which any added benefits to the patient would
`be unlikely or would produce unacceptable side effects.” Ex. 1009, 55972.
`Level of Ordinary Skill
`Petitioner argues that an ordinary artisan at the time of the ’166 patent
`invention would have “some combination of (a) experience with the research
`or development of pharmaceuticals; (b) the ability to gather and interpret
`pharmacokinetic and pharmacodynamics data including dose-response
`curves; and (c) the ability to understand results and findings presented or
`published by others in the field, including the references discussed in this
`Petition.” Pet. 15 (citing Ex. 1002 ¶¶ 38–39; Ex. 1004 ¶¶ 24–25).
`According to Petitioner, an ordinary artisan “would have, or would be a
`member of a team with individuals having, a Pharm.D. or Ph.D. with
`experience in clinical pharmacology, medicinal chemistry, or in a related
`field.” Id. at 16. In addition, Petitioner contends, an ordinary artisan “may
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`also have, or have access as part of a team to a person having, an M.D. with
`experience in the field of urology, with specific experience in sexual
`dysfunction.” Id.
`Patent Owner contends that Petitioner’s proposed definition of the
`skill level “does not require any expertise in the claimed subject matter”
`because Petitioner states that an ordinary artisan may have an M.D. with
`experience in urology.4 Prelim. Resp. 21. According to Patent Owner, an
`ordinary artisan “would have been a team including, or an individual having
`the collective experience of, at least: (1) a scientist having a Ph.D. in
`pharmacy, or an equivalent discipline, with approximately seven years of
`experience in preclinical and clinical pharmacokinetics and
`pharmacodynamics; and (2) a board certified M.D. with a specialty in the
`medical management of sexual dysfunction, including approximately seven
`years of experience in its research, diagnosis, and/or treatment.” Id. at 19–
`20.
`
`We agree with Patent Owner that an ordinary artisan would have, or
`have access to, an M.D. with a specialty in the medical management of
`sexual dysfunction. Indeed, Dr. Grass, the declarant for Petitioner, testifies
`that “as pharmaceutical development is an inherently collaborative process,
`the skilled artisan would have access to, or be part of a team including, other
`skilled individuals such as an M.D. with experience in the field of urology,
`
`
`4 Patent Owner represents that Petitioner’s definition is “without reference to
`the sexual dysfunction subject matter.” Prelim. Resp. 21. We disagree. The
`Petition specifically states that an ordinary artisan may have an M.D. with
`experience in urology, “with specific experience in sexual dysfunction.”
`Pet. 16.
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`with specific experience in sexual dysfunction.” Ex. 1002 ¶ 38.
`Aside from the medical expertise in managing sexual dysfunction, we
`do not discern other appreciable differences in the parties’ respective
`definitions of the level of ordinary skill in the art. Both parties contend that
`a person of ordinary skill in the art would have experience with and
`knowledge of pharmaceutical development, including preclinical and
`clinical pharmacokinetics and phamacodynamics. Pet. 15; Prelim. Resp. 20.
`Both parties acknowledge that an ordinary artisan would have access to, or
`be part of a multidisciplinary team of specialists. Prelim. Resp. 20; Ex. 1002
`¶ 38. Thus, on this record, we determine it is unnecessary to resolve any
`other perceived differences in the parties’ definitions of the level of ordinary
`skill in the art, as any distinction does not impact our Decision.
`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)).
`
`Obviousness over Daugan, SNDA, and the FDA Guideline
`Petitioner contends that claims 1–12 would have been obvious over
`the combined teachings of Daugan, SNDA, and the FDA Guideline.
`Pet. 20–46. Based on the current record, we determine Petitioner has
`established a reasonable likelihood that it would prevail in this assertion.
`Petitioner argues that SNDA qualifies as prior art under 35 U.S.C.
`§ 102(b). Pet. 11–14. Patent Owner disagrees. Prelim. Resp. 8–19. At this
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`stage of the proceeding, having reviewed the parties’ arguments and
`supporting evidence, we determine that Petitioner has presented sufficient
`evidence regarding the prior-art status of SNDA.
`To qualify as a printed publication, a reference “must have been
`sufficiently accessible to the public interested in the art” before the critical
`date. In re Cronyn, 890 F.2d 1158, 1160 (Fed. Cir. 1989). Whether a
`reference is publicly accessible is determined on a case-by-case basis based
`on the “facts and circumstances surrounding the reference’s disclosure to
`members of the public.” In re Lister, 583 F.3d 1307, 1311 (Fed. Cir. 2009).
`A reference is considered publicly accessible if it was disseminated or
`otherwise made available to the extent that persons interested and ordinarily
`skilled in the subject matter or art, exercising reasonable diligence, can
`locate it. Id.
`Petitioner points out that the “FDA approved sildenafil (VIAGRA®)
`on March 27, 1998.” Pet. 13 (citing Exs. 1008, 1032). Petitioner refers to a
`printout of an FDA webpage showing the table of contents of SNDA, and
`emphasizes the statement on the printout: “Date created: March 27, 1998.”
`Id. at 13; Ex. 1031. Patent Owner challenges that Petitioner has not shown
`the “Date created” language in Exhibit 1031 relates to the underlying
`documents (i.e., SNDA), and not merely the webpage with the table of
`contents of SNDA. Prelim. Resp. 12–13. In addition, Patent Owner
`contends that even if SNDA was created on the “Date created,” as shown in
`Exhibit 1031, “this does not alone establish” the public availability of SNDA
`on that date. Id. at 12–13.
`We agree with Patent Owner that Exhibit 1031, by itself, does not
`show that SNDA was publicly available on March 27, 1998. This exhibit,
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`however, is not the only evidence Petitioner relies on.5
`Under 21 C.F.R. § 314.430(e), after FDA sends an approval letter to
`the applicant of a new drug, certain data and information in the application
`are “immediately available for public disclosure.” These data and
`information include “a summary or summaries of the safety and
`effectiveness data and information submitted with or incorporated by
`reference in the application,” including “a Summary Basis of Approval
`(SBA) document that contains a summary of the safety and effectiveness
`data and information evaluated by FDA during the drug approval process.”
`21 C.F.R. § 314.430(e)(2)(ii).
`Petitioner asserts that an ordinary artisan would have been aware of
`the approval of sildenafil on March 27, 1998 because it “was publicized
`broadly that same day.” Pet. 13–14 (citing Exs. 1033–34). According to
`Petitioner, after FDA sent the approval letter to the applicant on March 27,
`1998, SNDA became “immediately available for public disclosure” under 21
`C.F.R. § 314.430(e). Id. at 12–13. Thus, Petitioner argues that an ordinary
`artisan, upon the approval of sildenafil on March 27, 1998, “could have
`requested and obtained the documents containing the safety and
`effectiveness information contained within” the SNDA. Id. at 14.
`Patent Owner challenges that Petitioner has not submitted any expert
`declaration to support its assertion. Prelim. Resp. 15. Patent Owner also
`questions whether SNDA corresponds to the “safety and effectiveness data”
`
`
`5 To the extent Patent Owner challenges the admissibility of Exhibit 1031
`(see Prelim. Resp. 12–13), the proper avenue is through a motion to exclude.
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,767 (Aug. 14,
`2012).
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`under 21 C.F.R § 314.430(e), pointing out that SNDA contains sections that
`“on their face appear to not be ‘safety and effectiveness data.’” Id. at 16. In
`addition, relying on a 2003 report by the Office of the Inspector General
`(Ex. 2005) and the 2014 CDER Manual of Policies and Procedures titled
`“Communicating Drug Approval Information” (Ex. 2006), Patent Owner
`contends that “immediately available” does not mean documents are
`available to the public on the very day a drug is approved. Id. at 16–17. We
`are not persuaded by Patent Owner’s arguments.
`First, the documents Patent Owner relies on, i.e., the report by the
`Office of the Inspector General and the CDER Manual of Policies and
`Procedures, are from 2003 and 2014, respectively. Id. at 16–17; Exs. 2005,
`2006. Sildenafil, however, was approved in 1998. Ex. 1032. Thus, at this
`stage of the proceeding, although we consider Exhibits 2005 and 2006, we
`accord them limited weight. Second, the majority of SNDA is directed to
`“Joint Clinical Reviews,” “Pharmacology Reviews,” “Statistical Review and
`Evaluation” including “Carcinogenicity Review,” and “Carcinogenicity
`Assessment Committee Report and FDA-CDER Rodent Carcinogenicity
`Database Factsheet.” Ex. 1008, 2–257, 264–496. Patent Owner does not
`dispute that these sections are directed to the “safety and effectiveness” of
`sildenafil. Thus, we are not persuaded that the mere inclusion of other
`sections would disqualify SNDA as the “safety and effectiveness data”
`under 21 C.F.R § 314.430(e). Third, we do not find the lack of expert
`testimony here fatal to the Petition. To be sure, direct evidence, such as a
`declaration, would have been more persuasive in establishing the public
`availability of SNDA. Nevertheless, for purposes of deciding whether to
`institute an inter partes review in this case, we find Petitioner presented has
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`sufficient indirect evidence, including the broadly publicized approval of
`sildenafil and the FDA regulation, regarding the prior-art status of SNDA.
`Substantively, Petitioner points to Daugan for teaching tadalafil as a
`“potent and selective” inhibitor of PDE5, and thus, is useful in treating
`sexual dysfunction. Pet. 31–32 (citing Ex. 1007, 1, 3–4, 6). Petitioner also
`relies on Daugan for teaching administering tadalafil orally to avoid “the
`disadvantages associated with i.c. administration.” Ex. 1007, 3–4; Pet. 32–
`33. Petitioner refers to Daugan for teaching tadalafil formulations
`comprising individual tablets or capsules containing “from 0.2-400mg of
`active compound, . . . for administration in single or multiple doses, once or
`several times per day.” Pet. 32 (citing Ex. 1007, 5).
`According to Petitioner, “[i]t was a routine matter for a person of
`ordinary skill in the art to identify a safe and effective dose range of tadalafil
`for the treatment of sexual dysfunction.” Pet. 33 (citing Ex. 1002 ¶ 71). In
`support, Petitioner refers to the FDA Guideline for teaching the development
`of dose-responsive information. Id. at 33–34.
`Petitioner contends that an ordinary artisan would have had a reason
`to look to SNDA to inform the dose-ranging studies for tadalafil because
`tadalafil and sildenafil “were known to have utility for the same indication,
`as well as share a common enzymatic target, PDE5, and the adverse events
`associated with PDE5 inhibition.” Id. at 34–35. In addition, according to
`Petitioner, tadalafil is a more potent inhibitor of PDE5 than sildenafil. Id. at
`35 (citing Ex. 1002 ¶ 75); compare Ex. 1007, 17 (showing IC50 for tadalafil
`is 2 nM) with Ex. 1008, 37 (showing IC50 for sildenafil is 3.5 nM).
`Petitioner argues that an ordinary artisan “would expect that lower
`doses of tadalafil would achieve similar efficacy as higher doses of sildenafil
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`in the treatment of sexual dysfunction.” Pet. 35 (citing Ex. 1002 ¶¶ 77–78).
`Petitioner further contends that an ordinary artisan would have appreciated
`the lower doses of tadalafil would result in lower frequencies of adverse
`events because they were known to be “clearly dose-related.” Id. at 35–36.
`As a result, Petitioner asserts, an ordinary artisan would have been motivated
`to look to the doses of sildenafil, as taught in SNDA, to identify the doses of
`tadalafil that are efficacious while retaining favorable adverse event profiles.
`Id.
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`Petitioner points to SNDA for teaching that sildenafil is
`therapeutically effective in treating ED at doses as low as 5 mg and as high
`as 100 mg. Id. at 36 (citing Ex. 1008, 126–28). Citing the testimony of
`Dr. Grass, Petitioner argues that “these doses, adjusted for the increased
`potency of tadalafil, are expected to be approximately equivalent to tadalafil
`doses of 2.8 mg and 57 mg, respectively.” Id. (citing Ex. 1002 ¶ 79); see
`also Ex. 1002 ¶ 77 (calculating the predicted doses of tadalafil based on the
`doses of sildenafil and the ratio of IC50 values).
`Petitioner emphasizes the teaching of SNDA that a dose of 25 mg
`sildenafil “is already fairly high on the dose-response curve.” Pet. 37 (citing
`Ex. 1008, 70). According to Petitioner, 25 mg of sildenafil is approximately
`equivalent to 15 mg of tadalafil. Id. (citing Ex. 1002 ¶¶ 77–78). Relying on
`the testimony of Dr. Grass, Petitioner contends that an ordinary artisan
`“would have reasonably expected a 15 mg dose of tadalafil to be near the top
`of the tadalafil dose-response curve based on the PDE5 inhibition results
`disclosed” in the SNDA. Id. (citing Ex. 1002 ¶ 78).
`Petitioner also refers to SNDA for repeatedly teaching that sildenafil
`is to be administered “not more than once per day,” and for conducting the
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`dose-ranging studies using once-daily dosing of sildenafil. Id. at 35 (citing
`Ex. 1008, 126, 132, 139, 146, 155, 217, 223, 238, 245, 251). In view of this
`teaching, Petitioner asserts that administering tadalafil in a unit dose of
`15 mg once daily meets the limitations of the challenged claim 1, i.e., “the
`unit dose must be between 1 to 20 mg and the total daily dose of tadalafil be
`no larger than 20 mg.” Id. at 38 (citing Ex. 1002 ¶ 82).
`At this stage of the proceeding, we find that Petitioner has offered
`sufficient evidence to institute trial. Although Patent Owner’s arguments are
`not unreasonable, they do not persuade us that we should decline to go
`forward with a trial.
`For example, Patent Owner challenges the assertion by Petitioner that
`the doses of tadalafil can be predicted based on the doses of sildenafil and
`the ratio of the IC50 values. Prelim. Resp. 24. Patent Owner contends that
`Dr. Grass, the declarant for Petitioner, cites no support for his testimony that
`“Potencies, as expressed in terms of IC50 and EC50 of known
`pharmaceuticals having a common target, can be compared to yield
`estimates of appropriate dosing.” Id. (quoting Ex. 1002 ¶ 55). We note that
`Dr. Grass cites Exhibits 1015 and 1025 to support the two sentences
`immediately preceding the quoted statement. See Ex. 1002 ¶ 55 (citing
`Ex. 1015, 50; Ex. 1025, 27). Considering this paragraph of Dr. Grass’s
`testimony as a whole, we are not persuaded that the challenged testimony is,
`as Patent Owner contends, entirely unsupported.
`In addition, according to Patent Owner, Petitioner has neither
`addressed the structural difference between tadalafil and sildenafil, nor
`explained the propriety of extrapolating in vitro data, such as IC50, to predict
`in vivo effects in patients. Id. at 24–25. Based on the current record, in
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`which Petitioner’s declarant has drawn plausible comparisons as to the
`relative potency of tadalafil to sildenafil, these are merely attorney argument
`as to how such structural or in vitro versus in vivo differences would affect
`the obviousness inquiry. We would be better equipped to resolve these
`factual disputes after the record is fully develop during trial.
`Patent Owner asserts that even if the doses of tadalafil can be
`predicted based on the doses of sildenafil and the ratio of IC50 values, it
`would have led to a maximum of at least 57 mg tadalafil, which corresponds
`to the maximum dose of 100 mg sildenafil. Prelim. Resp. 27. Thus,
`according to Patent Owner, an ordinary artisan “would not have been
`motivated to limit the dose of tadalafil to a maximum of 20 mg per day, as
`claimed.” Id. Based on the current record, we are not persuaded by this
`argument.
`As Petitioner points out, the FDA Guideline teaches that
`Historically, drugs have often been initially marketed at what
`were later recognized as excessive doses (i.e., doses well onto
`the plateau of the dose-response curve for the desired effect),
`sometimes with adverse consequences. . . . What is most helpful
`in choosing the starting dose of a drug is knowing the shape and
`location of the population (group) average dose-response curve
`for both desirable and undesirable effects. Selection of dose is
`best based on that information, together with a judgment about
`the relative importance of desirable and undesirable effects.
`Pet. 33 (quoting Ex. 1009, 55973).
`Although SNDA teaches the maximum dose of 100 mg sildenafil, it
`also teaches that sildenafil is therapeutically effective in treating ED at doses
`as low as 5 mg. Ex. 1008, 126–28. In addition, SNDA teaches that a dose
`of 25 mg sildenafil “is already fairly high on the dose-response curve” (id. at
`70), and that the frequencies of adverse events are “clearly dose-related” (id.
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`at 95). Thus, an ordinary artisan would have taken these teachings into
`consideration in identifying the optimal maximum dose of tadalafil.
`Patent Owner further argues that “Petitioner’s obviousness analysis
`tries to merge ‘a maximum total dose of 20 mg per day’ and ‘one or more
`unit dose containing about 1 to about 20 mg’ together.” Prelim. Resp. 27.
`We are not persuaded. As we understand the Petition, Petitioner relies on
`the unit doses of sildenafil and the ratio of IC50 values to account for the unit
`doses of tadalafil. See Pet. 39–40 (citing Ex. 1002 ¶¶ 76–79). Petitioner
`then relies on the teaching in SNDA that sildenafil is administered “not more
`than once per day” to account for the maximum total dose per day. Id. at 35
`(citing Ex. 1008, 126, 132, 139, 146, 155, 217, 223, 238, 245, 251).
`Patent Owner argues that Petitioner improperly relies on the
`disclosure of the challenged ’166 patent (i.e., tadalafil in a 10 mg dosage
`form) to support the limitation of maximum daily dose. Prelim. Resp. 28
`(citing Pet. 28). We are not persuaded by this argument, either. Petitioner
`proposes that we construe claim 1 to require “the unit dose is in the range of
`1 to 20 mg and that the total daily dose does not exceed 20 mg” (Pet. 28),
`which Patent Owner does not dispute (Prelim. Resp. 22). Again, as we
`understand the Petition, in support of its proposed construction, Petitioner
`merely states that the most preferred dose disclosed in the ’166 patent
`satisfies the limitations of claim 1 because (1) a 10 mg dosage form meets
`the requirement of a “unit dose containing about 1 to about 20 mg;” and (2)
`when administered once per day, meets the requirement of “up to a
`maximum total dose of 20 mg per day.” See Pet. 28.
`In sum, based on the current record, we conclude that Petitioner has
`established a reasonable likelihood of prevailing on its assertion that claim 1
`
`16
`
`
`
`
`
`IPR2017-00323
`Patent 6,943,166 B1
`
`would have been obvious over the combined teachings of Daugan, SNDA,
`and the FDA Guideline.
`
`CONCLUSION
`For the foregoing reasons, we find that Petitioner has offered
`sufficient evidence to institute an inter partes review. The information
`presented in the Petition and accompanying evidence establishes a
`reasonable likelihood that Petitioner would prevail in showing the
`unpatentability of claim 1of the ’166 patent.
`At this stage of the proceeding, the Board has not made a final
`determination as to the construction of any claim term or the patentability of
`any challenged claim.
`
`ORDER
`
`Accordingly, it is
`ORDERED that pursuant to 35 U.S.C. § 314, an inter partes review is
`hereby instituted to determine whether claims 1–12 of the ’166 patent would
`have been obvious over the combination of Daugan, SNDA, and the FDA
`Guideline.
`FURTHER ORDERED that pursuant to 35 U.S.C. § 314(a), inter
`partes review of the ’166 patent is hereby instituted commencing on the
`entry date of this Order, and pursuant to 35 U.S.C. § 314(c) and 37 C.F.R.
`§ 42.4, notice is hereby given of the institution of a trial.
`
`
`
`
`
`
`
`
`
`
`
`
`17
`
`
`
`IPR2017-00323
`Patent 6,943,166 B1
`
`PETITIONER:
`
`Steven W. Parmelee
`Michael T. Rosato
`Jad A. Mills
`WILSON SONSINI GOODRICH & ROSATI
`sparmelee@wsgr.com
`mrosato@wsgr.com
`jmills@wsgr.com
`
`PATENT OWNER:
`
`Mark J. Feldstein
`Joshua L. Goldberg
`Yieyie Yang
`Maureen D. Queler
`FINNEGAN, HENDERSON, FARABOW,
` GARRETT & DUNNER, LLP
`mark.feldstein@finnegan.com
`joshua.goldberg@finnegan.com
`yieyie.yang@finnegan.com
`maureen.queler@finnegan.com
`
`Mark J. Stewart
`Dan L. Wood
`Gerald P. Keleher
`ELI LILLY AND COMPANY
`stewart_mark@lilly.com
`wood_dan_l@lilly.com
`keleher_gerald@lilly.com
`
`
`
`
`18
`
`
`
`
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