Paper No. __
`
`Filed: June 9, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`INTELGENX CORPORATION
`Petitioner
`
`v.
`
`ICOS CORPORATION
`Patent Owner
`
`IPR2016-00678
`Patent No. 6,943,166
`
`Patent Owner’s Preliminary Response
`
`
`
`
`
`
`
`
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................... 1
`
`BACKGROUND ............................................................................................. 4
`
`A.
`
`B.
`
`C.
`
`The Parties ............................................................................................. 4
`
`Overview of U.S. Patent 6,943,166 to Pullman .................................... 5
`
`Prosecution History ............................................................................... 8
`
`III. CLAIM CONSTRUCTION .......................................................................... 11
`
`IV. GROUNDS OF ALLEGED UNPATENTABILITY .................................... 12
`
`V.
`
`THE PETITION SHOULD BE DENIED FOR FAILING TO
`ADDRESS AN ESSENTIAL CLAIM ELEMENT ...................................... 12
`
`A.
`
`B.
`
`C.
`
`The Petition Must Address Each Claim Limitation with
`Particularly .......................................................................................... 13
`
`The Claimed “Unit Dose of About 1 to About 20 mg” and “a
`Maximum Total Dose of 20 mg per Day” Are Separate Claim
`Limitations ........................................................................................... 15
`
`The Petition Should Be Denied for Failure to Address the “a
`Maximum Total Dose of 20 mg per Day” Limitation ........................ 18
`
`VI. THE BOARD SHOULD DECLINE REVIEW OF PETITIONER’S
`REDUNDANT ARGUMENTS .................................................................... 23
`
`A.
`
`B.
`
`The Board Should Deny Institution Where the Same or
`Substantially
`the Same Prior Art or Arguments Were
`Previously Presented ........................................................................... 23
`
`Both Grounds Should Be Denied as Redundant to the Art and
`Arguments Previously Considered and Overcome During
`Prosecution .......................................................................................... 24
`
`1.
`
`The First Ground Relies on Art and Arguments
`Previously Considered and Overcome ...................................... 24
`
` i
`
`
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`The Second Ground Fails to Present Persuasive Evidence
`to Supplement the Record Already Considered by the
`Office......................................................................................... 29
`
`The First Ground Should Also Be Denied as Vertically
`Redundant to the Second Ground ............................................. 31
`
`Denial Under § 325(d) Is Appropriate in This Case ................. 33
`
`2.
`
`3.
`
`4.
`
`VII. CONCLUSION .............................................................................................. 35
`
`
`
`
`ii
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`Federal Cases
`
`Abbott Labs. v. Baxter Pharm. Prods., Inc., 334 F.3d 1274 (Fed. Cir. 2003) ........... 9
`
`In re Wilson, 424 F.2d 1382 (C.C.P.A. 1970) .................................................. 14, 16
`
`Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111 (Fed.
`Cir. 2004) ..............................................................................................................16
`
`Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., --F.3d--, 2016 WL 2620512
`(Fed. Cir. May 9, 2016) ........................................................................................13
`
`Merck & Co. v. Teva Pharms. USA, Inc., 395 F.3d 1364 (Fed. Cir. 2005) ...... 14, 16
`
`Nike, Inc. v. Adidas AG, 812 F.3d 1326 (Fed. Cir. 2016) ........................................18
`
`ResQNet.com, Inc. v. Lansa, Inc., 594 F.3d 860 (Fed. Cir. 2010) ............................. 9
`
`Vederi, LLC v. Google, Inc., 744 F.3d 1376 (Fed. Cir. 2014) .................................16
`
`Patent Trial and Appeal Board Cases
`
`Conopco, Inc. v. The Proctor & Gamble Co., IPR2013-00510, Paper 9 (P.T.A.B.
`Feb. 12, 2014) .......................................................................................................21
`
`Funai Elec. Co. v. Gold Charm Ltd., IPR2015-01491, Paper 15 (P.T.A.B. Dec. 28,
`2015) ........................................................................................................ 24, 30, 35
`
`Harmonic, Inc. v. Avid Tech., Inc., IPR2013-00252, Paper 12 (P.T.A.B. Sept. 25,
`2013) ........................................................................................................ 15, 18, 31
`
`Hopkins Mfg. Corp. v. Cequent Performance Prods., Inc., IPR2015-00616, Paper 9
`(P.T.A.B. Aug. 17, 2015) ............................................................................... 14, 15
`
`Jiawei Tech. (HK) Ltd. v. Richmond, IPR2014-00937, Paper 22 (P.T.A.B. Dec. 16,
`2014) .............................................................................................................. 14, 18
`
`
`iii
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`Liberty Mutual Ins. Co. v. Progressive Casualty Ins. Co., CBM2013-00003
`(P.T.A.B. Oct. 25, 2012) .......................................................................... 31, 32, 33
`
`Medtronic, Inc. v. Lifeport Sci. LLC, IPR2014-00284, Paper 10 (P.T.A.B. June 25,
`2014) ............................................................................................................. passim
`
`Neil Ziegmann, N.P.Z., Inc. v. Stephens, IPR2015-01860, Paper 11 (P.T.A.B. Feb.
`24, 2016) ............................................................................................ 24, 29, 34, 35
`
`Prism Pharma Co. v. Choongwae Pharma Corp., IPR2014-00315, Paper 14
`(P.T.A.B. July 8, 2014) .........................................................................................24
`
`Statutes
`
`35 U.S.C. § 312(a)(3) ...............................................................................................13
`
`35 U.S.C. § 314 ....................................................................................................1, 14
`
`35 U.S.C. § 325(d) ........................................................................................ 1, 24, 35
`
`Other Authorities
`
`H.R. Rep. No. 112-98, pt.1, at 48 (2011) .......................................................... 23, 34
`
`Regulations
`
`37 C.F.R. § 42.104 ........................................................................................ 1, 14, 15
`
`37 C.F.R. § 42.108 ...............................................................................................1, 31
`
`37 C.F.R. § 42.6 .......................................................................................................21
`
`37 CFR § 42.20 ........................................................................................................15
`
`
`
`
`iv
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`Patent Owner’s Exhibit List
`
`Exhibits
`
`Description
`
`2001
`
`2002
`
`2003
`
`Daugan, U.S. Patent No. 6,140,329
`
`Daugan, U.S. Patent No. 5,859,006
`
`Eli Lilly & Co., Heritage,
`
`https://www.lilly.com/About/Heritage/heritage.aspx (last visited
`
`June 6, 2016)
`
`2004
`
`IntelGenX Techs. Corp., Annual Report (Form 10-K) (Mar. 30,
`
`2016), available at http://www.intelgenx.com/sec-filings-
`
`details/default.aspx?FilingId=11287482
`
`2005
`
`IntelGenX Corp., Films,
`
`http://www.intelgenx.com/product/films/default.aspx (last visited
`
`June 8, 2016)
`
`2006
`
`Background and Need for Legislation, H.R. Rep. No. 112-98 (2011)
`
`
`
` v
`
`
`
`

`
`I.
`
`INTRODUCTION
`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`The Board should deny institution for two reasons. First, the Petition fails to
`
`specify where each limitation of the challenged claims is found in or obvious from
`
`the cited references, and therefore it fails to demonstrate a reasonable likelihood of
`
`unpatentability under 35 U.S.C. § 314. See 37 C.F.R. §§ 42.104(b)(4), 42.108.
`
`Second, the Petition is redundant under 35 U.S.C. § 325(d).
`
`As to the first reason for denial, the Petition fails to address a key limitation
`
`in every claim of the ’166 patent, which covers the FDA-approved method of using
`
`tadalafil (the active ingredient in Cialis®) to treat erectile dysfunction. Ex. 1029
`
`(Cialis® label) at 1. Claim 1, the only independent claim, recites “[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 [tadalafil].” Ex. 1001 (’166 patent) at
`
`col. 14:65-15:15 (emphasis added). Although the Petition purports to show “where
`
`every element of claim 1 was taught in the prior art,” it fails to address the
`
`maximum-daily-dose claim limitation, ignoring the limitation in its claim charts,
`
`substantive argument, and two expert declarations. See Pet. at 20-25, 38-43; Ex.
`
`1005 (Hellstrom Declaration); Ex. 1007 (Patterson Declaration). By failing to
`
`
` 1
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`address every claim limitation, Petitioner has necessarily failed to establish a prima
`
`facie case. Denial of the Petition as a whole is required.
`
`Regarding the second independent reason for denial, both of the Petition’s
`
`two grounds are based on the same or substantially the same art and arguments that
`
`Patent Owner already overcame during prosecution. Neither the Office nor Patent
`
`Owner should be forced to revisit those redundant arguments.
`
`Petitioner’s first ground, which relies on a reference to Daugan (“Daugan
`
`’675”)1, is entirely duplicative of a rejection based on a related Daugan reference
`
`(“Daugan ’329”)2 that Patent Owner overcame during prosecution. Petitioner
`
`recognizes the redundancy of its argument but alleges Daugan ’675 “contains
`
`additional disclosures related to tadalafil’s potency” compared to Daugan ’329.
`
`Pet. at 18. The purported “additional disclosures” in Daugan ’675, however, are
`
`found in the ’166 patent specification and in yet another reference to Daugan
`
`(“Daugan ’006”)3 that was discussed in the ’166 patent specification and
`
`
`1 International Application Publication No. WO 97/03675 (Ex. 1002); see also Ex.
`
`1024 (’166 patent file history) at 221-244.
`
`2 U.S. Patent No. 6,140,329 (Ex. 2001).
`
`3 U.S. Pat. No. 5,859,006. (Ex. 2002).
`
`
` 2
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`considered by the Examiner. Ex. 1001 (’166 patent) at col. 2:12-21, 5:60-64
`
`(listing IC50 value for tadalafil); Ex. 1024 (’166 patent file history) at 530; Ex.
`
`2002 (Daugan ’006) at col. 48:50-64 (listing PDE5 IC50 values). Additionally,
`
`Petitioner does not rely on tadalafil’s potency in its alleged ground of invalidity.
`
`Pet. at 20-25.
`
`Petitioner’s second ground, Daugan ’675 in combination with materials from
`
`the New Drug Application (NDA) 20-895 for Sildenafil (“sildenafil SNDA”), is
`
`likewise redundant with the prosecution record. In addition to the Examiner
`
`having considered the related “NDA 20-895 (New Drug Application) Sildenafil for
`
`Male Impotence” materials (“sildenafil NDA approval documents”), the ’166
`
`patent specification expressly discloses sildenafil’s PDE5 receptor IC50 potency—
`
`the same information on which Petitioner relies from the sildenafil approval
`
`documents. Compare Ex. 1024 (’166 patent file history) at 578, and Ex. 1001
`
`(’166 patent) at col. 1:41-57, with Pet. at 26.
`
`Petitioner’s first ground is also vertically redundant to its second ground,
`
`which wholly subsumes the first. Yet, Petitioner offers no justification for
`
`maintaining both grounds. On this additional basis, the first ground should be
`
`denied.
`
`
` 3
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`Accordingly, the Petition should be denied because (1) it fails to address a
`
`key limitation—“a maximum total dose of 20 mg per day”—of every claim of the
`
`’166 patent and (2) both grounds are redundant to the same arguments and the
`
`same or substantially the same art that the Office already considered. Additionally,
`
`the first ground should be denied because it is vertically redundant to the second
`
`ground and Petitioner fails to articulate any distinction between them.
`
`II. BACKGROUND
`A. The Parties
`Patent Owner, ICOS Corporation, in partnership with Eli Lilly & Company
`
`(“Lilly”), developed, manufactures, and markets Cialis®. E.g., Ex. 1020 at 1.
`
`Based in Indianapolis, Indiana, Lilly is a worldwide leader in the development of
`
`innovative medicines. Ex. 2003 (Lilly Heritage) at 1.
`
`Petitioner, IntelGenX Corporation, is a Canadian company, established in
`
`2003 and headquartered in Montreal. Ex. 2004 (IntelGenX Form 10K) at 5.
`
`According to its website, Petitioner is attempting to develop a tadalafil formulation
`
`evidently to be marketed for the same indications and at the same doses (maximum
`
`of 20 mg per day) as Lilly’s approved Cialis® product, and selected tadalafil over
`
`the other two major PDE5 inhibitors marketed for the treatment of erectile
`
`dysfunction (sildenafil and vardenafil) for this purpose. Ex. 2005 (IntelGenX
`
`
` 4
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`Films) at 2. Petitioner claims that its proposed tadalafil product “is bioequivalent
`
`with the brand product, Cialis®” (Ex. 2004 (IntelGenX Form 10K) at 9), boasts
`
`that it “targets launch readiness ahead of Cialis® patent expiry” (Ex. 2005
`
`(IntelGenX Films) at 2), and intends to submit an application to the FDA later in
`
`2016 (Ex. 2004 (IntelGenX Form 10K) at 9).
`
`B. Overview of U.S. Patent 6,943,166 to Pullman
`The ’166 patent teaches inventive methods of treating sexual dysfunction by
`
`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 tadalafil. Ex. 1001 (’166 patent) at
`
`col. 14:65-15:15. It is based on the inventors’ surprising discovery, supported by
`
`extensive human clinical trials, that tadalafil administered in the claimed unit dose
`
`up to a maximum total dose of 20 mg per day provides effective treatment for
`
`erectile dysfunction (ED) without clinically significant side effects. Id. at col.
`
`2:22-51. For example, the claimed method provides efficacious treatment with a
`
`reduced tendency to cause the facial flushing and vision abnormalities adverse
`
`effects found with sildenafil that were thought to be both indicative of PDE5
`
`efficacy and inherent to treatment therewith. Id. at col. 2:22-32, 5:15-24.
`
`The ’166 patent has 12 claims; claim 1 is the sole independent claim.
`
`1. A method of treating sexual dysfunction in a patient in
`need thereof comprising orally administering one or more
`
` 5
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`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 tadalafil:]
`
`
`
`
`Id. at col. 14:65-15:15. The dependent claims recite further features, such as a unit
`
`
`
`dose of about 20 mg in claim 12. Id. at col. 15:18-16:20.
`
`The ’166 patent specification provides background information on tadalafil
`
`and sildenafil, the latter of which was the only approved PDE5 inhibitor for
`
`treating sexual dysfunction at the time of filing.
`
`First, the specification discusses Daugan ’006’s disclosure of a 2,000-fold
`
`range of unit doses (0.2 to 400 mg) and 10,000-fold PDE5 IC50 (in vitro potency4)
`
`range (1 nM to 10 µM) of “certain tetracyclic derivatives that are potent inhibitors
`
`of cGMP-specific PDE,” including tadalafil. Id. at 2:12-21. Both the ’166 patent
`
`
`4 The ’166 patent describes IC50 as “the concentration of a compound that results in
`
`50% enzyme inhibition in a single-dose response experiment.” Id. at 3:40-47.
`
`
` 6
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`specification and Daugan ’006 also disclose PDE5 IC50 values. Id. at 5:60-64
`
`(listing IC50 for tadalafil as 2.5 nM); see also Ex. 2002 (Daugan ’006) at col.
`
`48:50-64.
`
`Second, the specification notes that sildenafil is sold in 25, 50, and 100 mg
`
`tablets and has reported PDE5 IC50 values of 3 and 3.9 nM. Ex. 1001 at col. 1:44-
`
`52.
`
`The specification also describes extensive human clinical trials entailing
`
`administering doses up to 100 mg. Id. at col. 12:9-14:42.
`
`Example 5 discusses a “clinical pharmacology drug interaction study that
`
`evaluated the hemodynamic effects of concomitant administration of a selective
`
`PDE[5] inhibitor (i.e., Compound (I)) and short-acting nitrates on healthy male
`
`volunteers.” Id. at col. 12:8-33. As explained earlier in the ’166 patent,
`
`interactions with nitrates (e.g., nitroglycerin used by
`
`individuals having
`
`cardiovascular disease) are
`
`important because sildenafil potentiates
`
`their
`
`hypotensive effects. Id. at col. 1:58-2:11. Example 5 shows that tadalafil
`
`administered according to the claimed method was well-tolerated and resulted in
`
`“minimal, if any, effect on mean systolic blood pressure, and mean maximal
`
`nitroglycerin-induced decrease in systolic blood pressure.” Id. at col. 12:26-33.
`
`
` 7
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`Example 6 describes a study where tadalafil was administered at a range of
`
`doses “in both daily dosing and for on demand therapy.” Id. at col. 12:36-40.
`
`“Doses from 5 to 20 mg of Compound (I) were efficacious and demonstrated less
`
`than 1% [facial] flushing and no reports of vision abnormalities.” Id. at col. 12:40-
`
`42. It was also found that “a 10 mg dose of Compound (I) was fully efficacious
`
`and demonstrated minimal side effects.” Id. at col. 12:42-44.
`
`Example 7 discloses a third study involving over 200 men with mild to
`
`severe ED, who received 2 mg, 5 mg, 10 mg, and 25 mg doses on demand and not
`
`more than once every 24 hours. Id. at col. 12:65-13:4. “Comparisons revealed
`
`statistically significant differences in change in penetration ability between placebo
`
`and all dose levels of Compound (I).” Id. at col. 13:39-41. Indeed, all four doses
`
`“produced significant improvement, relative to placebo, in the sexual performance
`
`of men with erectile dysfunction,” without significant side effects. Id. at col.
`
`13:57-61, 14:25-36. The study also showed that doses above 25 mg up to 100 mg
`
`do not achieve further efficacy but adverse side effects continually increase. Id. at
`
`col. 14:1-36.
`
`Prosecution History
`
`C.
`The same references Petitioner relies on here were presented and considered
`
`during prosecution.
`
`
` 8
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`Applicant submitted both Daugan ’675 and the sildenafil NDA approval
`
`documents,5 which the Examiner acknowledged as presented and considered. Ex.
`
`1024 (’166 patent file history) at 221-244, 530, 578.
`
`The Examiner relied on the U.S. national phase entry of Daugan ’675,
`
`Daugan ’329, in initially rejecting all of the claims. E.g., Id. at 527. Specifically,
`
`like the Petitioner does here with Daugan ’675, the Examiner cited Daugan ’329 as
`
`“disclos[ing] the instant compound and a method of using it to treat sexual
`
`dysfunction,” as well as “oral administration and a dosage within the recited
`
`range.” Id.; see also id. at 576, 599, 628.
`
`In response, Applicant distinguished Daugan ’329 for two separate reasons:
`
`it “fails to teach or suggest [1] an oral dosage form containing about 1 to about 20
`
`mg of the claimed PDE5 inhibitor, or [2] its use in a method of treating sexual
`
`dysfunction using a maximum total dose of about 20 mg per day. Id. at 536
`
`
`5 Applicant’s identification of the sildenafil NDA approval documents in an
`
`Information Disclosure Statement is not an admission that they constitute prior art.
`
`E.g., ResQNet.com, Inc. v. Lansa, Inc., 594 F.3d 860, 866 (Fed. Cir. 2010); Abbott
`
`Labs. v. Baxter Pharm. Prods., Inc., 334 F.3d 1274, 1279 (Fed. Cir. 2003).
`
`
` 9
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`(emphasis added). For example, specifically addressing the second limitation,
`
`Applicant argued:
`
`• “the ’329 patent does not teach or suggest a low maximum daily dose
`
`for effective treatment of sexual dysfunction” (id. at 537, 589, 612-13
`
`(emphasis in original));
`
`• “[Daugan ’329] fails to teach or suggest . . . a maximum total dose of
`
`about 20 mg per day” (id. at 588);
`
`• “The ’329 patent contains no disclosure that would lead a person
`
`skilled in the art to consider using the presently claimed low unit dose
`
`and maximum daily dose of Compound (I)” (id. at 590); and
`
`• “The ’329 patent . . . fails to teach or suggest the specific unit
`
`dosage, maximum daily dosage, and the specific compound of the
`
`present invention that provides such new and unexpected benefits”
`
`(id. at 593, 613).
`
`Applicant further cited unexpected results from the unit dose and dose range
`
`of the claimed method, which surprisingly provides comparable efficacy to higher
`
`doses but with no or low side effects. Id. at 612, 855-59. In this regard, Applicant
`
`cited data in the specification showing that maximum daily doses in the range of 2
`
`mg to 100 mg are efficacious, but there were unpleasant adverse events when the
`
`
` 10
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`maximum daily dose exceeded about 20 mg per day. Id. at 612. Applicant
`
`explained that the low dose range claimed “has surprisingly low adverse side
`
`effects while still unexpectedly found to be efficacious.” Id. This was surprising,
`
`as further explained, because although “decreasing a dose of drug often decreases
`
`side effects, it also often decreases efficacy.” Id. at 857 (emphasis added).
`
`Therefore, the “observed divergence of retained efficacy from decreased side
`
`effects in [the claimed] substantially lower doses is unexpected.” Id. In support of
`
`these unexpected results, Applicant submitted two declarations from Dr. Gregory
`
`Sides, who testified that the “dramatic reduction in adverse events . . . coupled with
`
`an efficacy [comparable to higher doses] across the claimed dose range is an
`
`unexpected advance in the art.” Id. at 615-20, 860-864.
`
`The Examiner found Applicant’s unexpected results persuasive, concluding
`
`that the claimed low dose of tadalafil showed comparable efficacy to a higher dose
`
`but “dramatically reduced” adverse side effects. Id. at 875 (Notice of Allowance).
`
`III. CLAIM CONSTRUCTION
`The unexpired ’166 patent’s claims have not been construed in U.S.
`
`litigation.
`
`Petitioner proposes constructions for three claim terms:
`
`
` 11
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`• “compound having the structure”: compound recited by its chemical name
`
`in the specification (at col. 2:23-27, 2:60-62), shown in claim 1, and also
`
`known as “tadalafil”;
`
`• “female arousal disorder”: type of sexual dysfunction, more specifically a
`
`type of female sexual dysfunction; and
`
`• “free drug”: solid particles of drug not intimately embedded in a polymeric
`
`coprecipitate (i.e., as defined in the specification at col. 4:1-2).
`
`Pet. at 15-17. For the purposes of this preliminary response, Patent Owner does
`
`not contest these proposed constructions.
`
`IV. GROUNDS OF ALLEGED UNPATENTABILITY
`Petitioner raises two grounds for alleged obviousness:
`
`1) Claims 1-12 are unpatentable as obvious over Daugan ’675; and
`
`2) Claims 1-12 are unpatentable as obvious over Daugan ’675 and the
`
`sildenafil citrate (Viagra®) Approval Package for New Drug
`
`Application No. 20-895.
`
`V. THE PETITION SHOULD BE DENIED FOR FAILING TO
`ADDRESS AN ESSENTIAL CLAIM ELEMENT
`
`It is Petitioner’s burden to demonstrate that it is entitled to the relief it
`
`requests, which includes showing where each element of the claim is allegedly
`
`found in the cited prior art patents and publications. Here, Petitioner ignores the
`
`
` 12
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`claim limitation “a maximum total daily dose of 20 mg per day,” addressing only
`
`the separate limitation “one or more unit dose containing about 1 to about 20 mg.”
`
`Nowhere in the substantive argument, claim charts, or expert declarations for either
`
`of its proposed grounds does Petitioner address the maximum-daily-dose limitation
`
`or explain why a person of ordinary skill would have been motivated to modify the
`
`cited references to arrive at the maximum-daily-dose limitation. Accordingly,
`
`Petitioner fails to carry its burden, and the Petition should be denied in its entirety.
`
`A. The Petition Must Address Each Claim Limitation with
`Particularly
`A petition must “identif[y] . . . with particularity . . . the grounds on which
`
`the challenge to each claim is based.” 35 U.S.C. § 312(a)(3). As the Federal
`
`Circuit has recently explained, “[i]t is of the utmost importance that petitioners in
`
`the IPR proceedings adhere to the requirement that the initial petition identify
`
`‘with particularity’ the ‘evidence that supports the grounds for the challenge to
`
`each claim.’” Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., --F.3d--, 2016
`
`WL 2620512, at *8 (Fed. Cir. May 9, 2016). Denial is required where, as here,
`
`Petitioner fails to meet this basic requirement.
`
`More specifically, the statutorily required particularity means that a petition
`
`“must specify where each element of the claim is found in the prior art patents or
`
`printed publications relied upon.” Hopkins Mfg. Corp. v. Cequent Performance
`
`
` 13
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`Prods., Inc., IPR2015-00616, Paper 9, at 7 (P.T.A.B. Aug. 17, 2015) (citing 37
`
`C.F.R. § 42.104(b)(4) (emphasis added)). In this regard, “[a]ll words in a claim
`
`must be considered in judging the patentability of that claim against the prior art.”
`
`In re Wilson, 424 F.2d 1382, 1385 (C.C.P.A. 1970); see also Merck & Co. v. Teva
`
`Pharms. USA, Inc., 395 F.3d 1364, 1372 (Fed. Cir. 2005) (claims should be
`
`construed to give meaning to every term).
`
`“Additionally, the petition must identify . . . ‘specific portions of the
`
`evidence that support the challenge.’” Hopkins Mfg., IPR2015-00616, Paper 9, at 7
`
`(quoting 37 C.F.R. § 42.104(b)(5)). A petition must be rejected where it fails to
`
`identify specific portions of the evidence that support the challenge, because
`
`without such specificity the petitioner cannot establish a reasonable likelihood of
`
`unpatentability under 35 U.S.C. § 314.
`
`For example, as the Board held in Jiawei Tech. (HK) Ltd. v. Richmond,
`
`when it denied institution, a petitioner who fails to address all the claim limitations
`
`fails to “demonstrate[] a reasonable likelihood of success in showing the subject
`
`matter of [the challenged claims] would have been obvious.” IPR2014-00937,
`
`Paper 22, at 7-8 (P.T.A.B. Dec. 16, 2014). Similarly, in Medtronic, Inc. v. Lifeport
`
`Sci. LLC, institution was denied on claims where the petitioner failed to meet the
`
`requirement that “each limitation in a challenged claim must be addressed.”
`
`
` 14
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`IPR2014-00284, Paper 10, at 19-20 (P.T.A.B. June 25, 2014) (citing 37 C.F.R.
`
`§ 42.104(b)(4) (failing to address claim limitation in claim charts or substantive
`
`argument); see also Harmonic, Inc. v. Avid Tech., Inc., IPR2013-00252, Paper 12,
`
`at 35-36 (P.T.A.B. Sept. 25, 2013) (denying institution on ground where petition
`
`“fails to provide a sufficient and credible explanation as to how [the cited
`
`reference] teaches the features recited in these claims limitations”).
`
`Finally, as a matter of both law and equity, “all vagueness and ambiguity” in
`
`a petitioner’s arguments are resolved against the petitioner because it bears the
`
`burden to establish that it is entitled to the requested relief. Hopkins Mfg.,
`
`IPR2015-00616, Paper 9, at 7; 37 CFR § 42.20(c).
`
`B.
`
`The Claimed “Unit Dose of About 1 to About 20 mg” and “a
`Maximum Total Dose of 20 mg per Day” Are Separate
`Claim Limitations
`
`Under well-settled legal principles and as confirmed by the prosecution
`
`history, “a maximum total dose of 20 mg per day” and “one or more unit dose
`
`containing about 1 to about 20 mg” are separate limitations, and both must be
`
`addressed. Indeed, Petitioner does not even attempt to argue otherwise—it simply
`
`ignores the maximum-daily-dose limitation.
`
`The Federal Circuit has provided clear guidance that each separate recitation
`
`in a claim is presumptively a distinct limitation. This is the case because, with
`
`
` 15
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`limited exceptions, “all claim terms are presumed to have meaning in a claim.”
`
`Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1119
`
`(Fed. Cir. 2004). Thus, claims should be construed to give meaning to every term
`
`and constructions that render terms superfluous are routinely rejected. E.g., Merck
`
`& Co., 395 F.3d at 1372; see also Vederi, LLC v. Google, Inc., 744 F.3d 1376,
`
`1382-83 (Fed. Cir. 2014). Likewise, in the context of validity—as is at issue
`
`here—“[a]ll words in a claim must be considered in judging the patentability of
`
`that claim against the prior art.” In re Wilson, 424 F.2d at 1385.
`
`The prosecution history here is consistent with the legal presumption and
`
`reinforces that “one or more unit dose containing about 1 to about 20 mg,” and “a
`
`maximum total dose of 20 mg per day” are two separate limitations. For example,
`
`responding to the first office action, Applicant stressed that the claimed invention
`
`recited both a “unit dose of about 1 to about 20 mg” and “using a maximum total
`
`dose of about 20 mg per day,” explaining that neither was disclosed in the cited
`
`reference. Ex. 1024 (’166 patent file history) at 536 (“As discussed hereafter, the
`
`cited reference fails to teach or suggest an oral dosage form containing about 1 to
`
`about 20 mg of the claimed PDE5 inhibitor, or its use in a method of treating
`
`sexual dysfunction using a maximum total dose of about 20 mg per day.”
`
`(emphasis added)).
`
`
` 16
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`Indeed, throughout prosecution, Applicant repeatedly emphasized that the
`
`maximum-daily-dose limitation was one of several features that each distinguished
`
`the claimed invention over the cited prior art reference, Daugan ’329. Id. at 537
`
`(“the ’329 patent does not teach or suggest a low maximum daily dose for effective
`
`treatment of sexual dysfunction”); id. at 588 (“[Daugan ’329] fails to teach or
`
`suggest . . . a maximum total dose of about 20 mg per day.”); id. at 593 (“The ’329
`
`patent . . . fails to teach or suggest the specific unit dosage, maximum daily dosage,
`
`and the specific compound of the present invention that provides such new and
`
`unexpected benefits.”). The Daugan references addressed during prosecution
`
`likewise distinguish between unit dose size and the maximum daily dose. E.g., Ex.
`
`2001 (Daugan ’329) at col. 3:48-54 (disclosing daily oral dosages in the range of
`
`0.5-800 mg unit doses of 0.2-400 mg); Ex. 1002 (Daugan ’675) at col. 5:1-5
`
`(same).
`
`Thus, the prosecution-history-supported presumption—not addressed much
`
`less overcome by Petitioner—is that “one or more unit dose containing about 1 to
`
`about 20 mg,” and “a maximum total dose of 20 mg per day” are two separate
`
`limitations.
`
`
` 17
`
`

`
`IPR2016-00678
`Patent Owner’s Preliminary Response
`U.S. Patent 6,943,166
`
`
`C. The Petition Should Be Denied for Failure to Address the “a
`Maximum Total Dose of 20 mg per Day” Limitation
`
`The Petition sets forth argument (Pet. at 20-25, 38-43), including claim
`
`charts (Pet. a