`
`IPR2017-01673
`U.S. Patent No. 6,790,459
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________________________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`Aurobindo Pharma USA Inc.
`Petitioners,
`v.
`Andrx Labs, LLC
`Patent Owner
`____________________________________________
`Case IPR2017-01673
`U.S. Patent No. 6,790,459
`____________________________________________
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`UNDER 37 C.F.R. § 42.107
`
`

`

`
`
`IPR2017-01673
`U.S. Patent No. 6,790,459
`
`I. 
`II. 
`
`TABLE OF CONTENTS
`
`Introduction ...................................................................................................... 1 
`Background ...................................................................................................... 5 
`A. 
`State of the Art in November 2000 ....................................................... 5 
`B. 
`Clinical Development and Approval of Fortamet® .............................. 6 
`C. 
`The ’459 Patent ..................................................................................... 7 
`D. 
`Litigation Involving the ’459 Patent ................................................... 10 
`E. 
`Alleged Prior Art Relied on by Petitioner ........................................... 12 
`III.  Level of Ordinary Skill in the Art ................................................................. 16 
`IV.  Claim Construction ........................................................................................ 17 
`A. 
`“Membrane” ........................................................................................ 17 
`B. 
`“Dinnertime” or “At Dinner” .............................................................. 19 
`C. 
`“Cmax” .................................................................................................. 19 
`D. 
`“Tmax” ................................................................................................... 19 
`E. 
`“AUC0-24” ............................................................................................ 20 
`F. 
`Other Claim Terms Not Requiring Construction ................................ 20 
`The Petition Fails to Establish a Reasonable Likelihood that Any of Claims
`1-21 is Anticipated by Chen (Ground I) ........................................................ 21 
`VI.  The Petition Fails to Establish a Reasonable Likelihood that Any of Claims
`1-21 is Obvious Over Cheng in View of Timmins, Tucker, and Lewis
`(Ground II) ..................................................................................................... 23 
`A. 
`Petitioner’s Conclusory Assertions Cannot Support a Finding of
`Motivation to Combine with a Reasonable Expectation of Success ... 23 
`Arguments in the Akhlaghi Declaration Regarding Tmax Cannot
`Support a Finding of Motivation to Combine with a Reasonable
`Expectation of Success ........................................................................ 27 
`VII.  Objective Indicia Support the Non-Obviousness of the Challenged
`Claims ............................................................................................................ 29 
`VIII.  Conclusion ..................................................................................................... 32 
`
`
`
`V. 
`
`B. 
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`IPR2017-01673
`U.S. Patent No. 6,790,459
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Intendis GMBH v. Glenmark Pharmacuetical Inc., USA,
`822 F.3d 1355 (Fed. Cir. 2016) .......................................................................... 24
`InTouch Technologies v. VGO Communications, Inc.,
`751 F.3d 1327 (Fed. Cir. 2014) .................................................................... 23, 27
`In re Katz,
`687 F.2d 450 (C.C.P.A. 1982) ............................................................................ 21
`In re Lee,
`277 F.3d 1338 (Fed. Cir. 2002) .......................................................................... 24
`In re NuVasive, Inc.,
`842 F.3d 1376 (Fed. Cir. 2016) .................................................................... 24, 26
`In re Van Os,
`844 F.3d 1359 (Fed. Cir. 2017) .................................................................... 24, 26
`Kinetic Technologies, Inc. v. Skyworks Solutions, Inc.,
`IPR2014-00529, Paper 8 (P.T.A.B. Sept. 23, 2014) ............................................. 5
`Kingston Technology. Co. v. Imation Corp.,
`IPR2015-00066, Paper 19 (P.T.A.B. Mar. 24, 2016) ......................................... 28
`Personal Web Technologies, LLC v. Apple, Inc.,
`848 F.3d 987 (Fed. Cir. 2017) ...................................................................... 24, 27
`Sinorgchem Co. v. International Trade Commission,
`511 F.3d 1132 (Fed. Cir. 2007) .............................................................. 18, 19, 20
`Docketed Cases
`Sciele Pharma, Inc. et al v. Lupin Ltd. et al.,
`No. 1-09-cv-00105 (D. Md.) ............................................................................... 11
`Shionogi Inc. and Andrx Labs. L.L.C. v. Aurobindo Pharma Ltd. et al.,
`Civ. Act. No. 1:17-cv-00072-MSG (D. Del.) ..................................................... 10
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`IPR2017-01673
`U.S. Patent No. 6,790,459
`
`
`Shionogi Inc. et al. v. Qingdao Baheal Pharmaceutical Co. Ltd.,
`Civ. Act. No. 17-cv-1347-MSG (D. Del.) .......................................................... 11
`Takeda Pharmaceutical Co., Ltd., et. al. v. Mylan, Inc., et. al.,
`No. 2-12-cv-00026 (W.D. Pa.) ........................................................................... 12
`Takeda Pharmaceutical Company Limited et al v. Mylan, Inc. et al.,
`No. 1-12-cv-00024 (S.D.N.Y.) ........................................................................... 11
`Takeda Pharmaceutical Company Limited et al v. Mylan, Inc. et al.,
`No. 1-12-cv-02038 (S.D.N.Y.) ........................................................................... 11
`Statutes, Codes & Regulations
`35 U.S.C. § 102(g) ................................................................................................... 22
`35 U.S.C. § 314 .......................................................................................................... 1
`37 C.F.R. § 42.6(a)(3) .............................................................................................. 28
`37 C.F.R. § 42.22(a)(2) ............................................................................................ 28
`37 C.F.R. § 42.108 ..................................................................................................... 1
`American Inventors Protection Act of 1999 ............................................................ 22
`Intellectual Property and High Technology Technical Amendments
`Act of 2002 ......................................................................................................... 22
`Other Authorities
`December 11, 2002 Examination Guidelines for 35 U.S.C. § 102(e) ..................... 22
`MPEP § 706.02(F)(1)(I)(C)(3) ........................................................................... 21, 22
`MPEP § 2132(III) ..................................................................................................... 21
`MPEP § 2136.04 ...................................................................................................... 21
`
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`I.
`
`Introduction
`
`IPR2017-01673
`U.S. Patent No. 6,790,459
`
`Aurobindo petitions to institute inter partes review of U.S. Patent No.
`
`6,760,459 (“the ’459 patent”) (Ex. 1001) based on legally deficient grounds and on
`
`references already considered and rejected by the Patent Office over the course of a
`
`rigorous examination. The Petition and the accompanying Declaration of Dr.
`
`Fatemeh Akhlaghi (hereinafter “the Akhlaghi Declaration”) (Ex. 1009) not only
`
`reargue positions that the Patent Office previously considered and rejected before
`
`issuing the challenged claims, but also assert a reference that does not even qualify
`
`as prior art to the ’459 patent. As such, the Petition fails to establish that Petitioner
`
`is reasonably likely to prevail in establishing the unpatentability of any challenged
`
`claim. Accordingly, the Board should decline to institute inter partes review. See
`
`35 U.S.C. § 314; 37 C.F.R. § 42.108.
`
`Petitioner has challenged claims 1-21 of the ’459 patent. The challenged
`
`claims describe the important discovery of a method for lowering blood glucose
`
`levels in human patients with non-insulin-dependent diabetes mellitus (“NIDDM,”
`
`also known as type 2 diabetes) using a controlled release once-a-day dosage form
`
`of metformin that provides effective control of blood glucose levels, and that is
`
`superior to prior methods. More specifically, the challenged claims recite, inter
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`alia, a method for lowering blood glucose levels in human patients needing
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`treatment for NIDDM, the method comprising:
`
` orally administering on a once-a-day basis at least one oral controlled
`
`release dosage form comprising an effective dose of metformin or a
`
`pharmaceutically acceptable salt thereof and an effective amount of a
`
`controlled release carrier;
`
` wherein following oral administration of a single dose, the dosage
`
`form provides a mean time to maximum plasma concentration (Tmax)
`
`of metformin at from 5.5 to 7.5 hours after administration following
`
`dinner; and
`
` wherein the administration provides:
`o a mean AUC0-24 of 22,590 ± 3,626 ng·hr/mL and mean Cmax of
`
`2,435 ± 630 ng/mL on the first day of administration; and
`o a mean AUC0-24 of 24,136 ± 7,996 ng·hr/mL and mean Cmax of
`
`2,288 ± 736 ng/mL on the 14th day of administration;
`
` for administration of a 2,000 mg once-a-day dose of metformin.
`
`’459 patent, col. 22 ll. 13-35. The claimed methods are embodied in the approved
`
`use of Fortamet® Extended Release Tablets, Patent Owner’s drug used in the
`
`management of type 2 diabetes.
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`The Petition asserts two invalidity grounds, neither of which should be
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`
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`instituted.
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`First, Petitioner asserts that claims 1-21 are anticipated by Chen (Ex. 1011)
`
`– a reference that does not even qualify as prior art to the ’459 patent.1 Petitioner
`
`fails to (and cannot) explain how Chen so qualifies under any section of pre-AIA
`
`35 U.S.C. § 102. Accordingly, Petitioner has failed to meet its burden of
`
`establishing a reasonable likelihood that it will prevail on at least one claim based
`
`on anticipation by Chen, and Ground I should be denied.
`
`Second, Petitioner asserts that claims 1-21 are obvious over Cheng (Ex.
`
`1002) in view of Timmins (Ex. 1013), Tucker (Ex. 1005) and Lewis (Ex. 1003).2
`
`However, Cheng, Timmins, and Lewis were already considered and rejected by the
`
`1 See International Patent Application Publication No. WO 00/12097 (hereinafter
`
`“Chen” or Ex. 1011).
`
`2 See International Patent Application Publication No. WO 99/47125 (hereinafter
`
`“Cheng” or Ex. 1002); International Patent Application Publication No. WO
`
`99/47128 (hereinafter “Timmins” or Ex. 1013); Tucker, G. T. et al., Br. J.
`
`Pharmacol. 1981, 12, 235-46 (hereinafter “Tucker” or Ex. 1005); International
`
`Patent Application Publication No. WO 00/28989 (hereinafter “Lewis” or Ex.
`
`1003).
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`Patent Office during prosecution of the application that issued as the ’459 patent
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`over the course of an examination that included three Office Actions. Tucker, the
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`only reference that the Patent Office did not previously consider, is cited by
`
`Petitioner for its alleged disclosure of certain pharmacokinetic parameters provided
`
`by prior immediate release dosage forms of metformin, but neither the Petition nor
`
`the Akhlaghi Declaration explain how this secondary reference overcomes the
`
`deficiencies of Cheng, Timmins, and Lewis found by the Patent Office, beyond
`
`mere conclusory assertions. Even taking the arguments in the Petition at face
`
`value, Petitioner fails to show that a person of ordinary skill in the art (“POSA”) at
`
`the time of the ’459 patent would have been motivated to combine the asserted
`
`prior art references with a reasonable expectation of success in arriving at the
`
`claimed dosage forms. In fact, the Petition never even states that a POSA would
`
`make such a combination in a way that would provide the pharmacokinetic
`
`parameters recited in the challenged claims, let alone a reason why they would do
`
`so. Accordingly, Petitioner also has failed to meet its burden of establishing a
`
`reasonable likelihood that it will prevail on at least one claim based on the
`
`combination presented in Ground II. Therefore, Ground II should be denied.
`
`Each of the Grounds in the Petition thus falls far short of providing the
`
`“articulated reasoning with rational underpinning” necessary to support a legal
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`conclusion of anticipation or obviousness. Kinetic Techs., Inc. v. Skyworks Sols.,
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`Inc., IPR2014-00529, Paper 8 at 16 (P.T.A.B. Sept. 23, 2014). Petitioner has not
`
`established a reasonable likelihood of prevailing on any of its anticipation or
`
`obviousness grounds. Accordingly, inter partes review should not be instituted.
`
`II. Background
`
`A.
`
`State of the Art in November 2000
`
`Metformin is a short-acting drug used to treat non-insulin-dependent
`
`diabetes mellitus (NIDDM). ’459 patent, col. 1 ll. 57-59. At the time of filing of
`
`the ’459 patent in November 2000, metformin hydrochloride was marketed as
`
`Glucophage® by Bristol-Myers Squibb in the United States. Id. col. 1 ll. 62-64.
`
`At the time, there was no fixed dosage regimen for Glucophage® to manage
`
`hyperglycemia in patients with diabetes mellitus – instead, dosages were
`
`individualized to each patient using 500 mg, 850 mg, or 1,000 mg tablets based on
`
`both effectiveness and tolerance, while not exceeding the maximum recommended
`
`dose of 2,550 mg per day. Id. col. 1 l. 65 – col. 2 l. 3. However, because
`
`metformin is a short-acting drug, patients had to take the medication two or three
`
`times each day. Id. col. 2 ll. 5-7. Such frequent dosing typically led to reduced
`
`patient compliance and increased adverse events. See id. col. 1 ll. 15-19; col. 2 ll.
`
`5-7. In the case of metformin, such adverse events include the potentially
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`dangerous side-effects of anorexia, nausea, and vomiting. Id. col. 2 ll. 7-9; col. 20
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`ll. 47-49.
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`At the time of the ’459 patent, there was thus a need in the art for a method
`
`of controlling blood glucose levels in patients with type 2 diabetes using a safe and
`
`effective dosage form of metformin that would enable patients with type 2 diabetes
`
`to take their medication once-a-day, thereby improving patient compliance and
`
`reducing adverse events.
`
`B. Clinical Development and Approval of Fortamet®
`
`To address these shortcomings in the prior art treatments for type 2 diabetes,
`
`the inventors of the ’459 patent developed Fortamet®, a novel extended release
`
`dosage form of metformin. Results from clinical studies demonstrated that
`
`Fortamet® was comparable to immediate-release metformin in terms of efficacy
`
`and safety, while providing for a more convenient once-daily dosage regimen. See
`
`Apr. 27, 2004 Letter from the FDA Approving NDA 21-574 (hereinafter “the
`
`Fortamet® FDA Approval Letter”) (Ex. 2001); Fortamet® FDA Label (Rev.
`
`02/10) at 8-12, 28 (Ex. 2002). The FDA approved Fortamet® for use in managing
`
`type 2 diabetes on April 27, 2004. See Fortamet® FDA Approval Letter (Ex.
`
`2001).
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`C. The ’459 Patent
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`The ’459 Patent, entitled “Methods For Treating Diabetes Via
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`Administration of Controlled Release Metformin,” issued from U.S. Patent
`
`Application No. 09/705,625, filed on November 3, 2000 (“the ’625 application”).
`
`The named inventors are Xiu Xiu Cheng, Chih-Ming Chen, Steve Jan, and Joseph
`
`Chou.
`
`During prosecution of the ’625 application, the Patent Office was aware of,
`
`and specifically considered, Cheng (Ex. 1002), Timmins (Ex. 1013), and Lewis
`
`(Ex. 1003), on which Petitioner now relies. As an initial matter, Applicant
`
`discussed both Timmins and Cheng in the Background of the Invention section of
`
`the ’459 patent specification. ’459 patent, col. 2 ll. 35-48. In addition, in the first
`
`Office Action, the Examiner rejected the pending claims over Cheng and Lewis
`
`under pre-AIA 35 U.S.C. § 102, and over either Cheng or Lewis alone or in
`
`combination with a secondary reference, Drug Facts and Comparisons (hereinafter
`
`“DFC”), under pre-AIA 35 U.S.C. § 103. Office Action mailed Dec. 31, 2001 for
`
`the ’625 application, at 3-6 (Ex. 1006 at 254-57) The Examiner stated that Lewis
`
`and Cheng “teach controlled release metformin compositions” and argued that the
`
`“claimed functional limitations are inherent.” Id. at 5 (Ex. 1006 at 256). The
`
`Examiner again rejected the claims as allegedly anticipated by Cheng in the second
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`Office Action, reiterating that Cheng “discloses controlled release
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`antihyperglycemic dosage form[s] that ha[ve] the same composition taught by the
`
`specification as providing the instant mean fluctuation indexes.” Office Action
`
`mailed Oct. 22, 2002 for the ’625 application, at 4-5 (Ex. 1006 at 232-33). Finally,
`
`in a third Office Action, the Examiner rejected the claims as allegedly obvious
`
`over, inter alia, Lewis in combination with secondary references DFC and Chiao
`
`(Remington, 1995), stating that “it would have been obvious to one skilled in the
`
`art at the time of the invention to combine [Lewis] with Chiao and DFC… with the
`
`motivation of providing controlled delivery of metformin over a desired period of
`
`time to lower blood glucose levels when an individual is in the fed state.” Office
`
`Action mailed July 14, 2003 for the ’625 application, at 3-4 (Ex. 1006 at 195-96).
`
`In the same Office Action, the Examiner rejected the claims as allegedly obvious
`
`over Cheng and DFC, stating that “it would have been obvious to one skilled in the
`
`art at the time of the invention to manipulate the release profile of [Cheng] in
`
`accordance with the teachings in [U.S. Patent No. 3,845,770] and lower blood
`
`glucose levels accordingly with the motivation of providing controlled delivery of
`
`metformin over a desired period of time and to administer the compositions at
`
`dinner or at a fed state with the motivation of regulating sugar levels.” Id. at 4-5
`
`(Ex. 1006 at 196-97). The rationale underlying these rejections was the same as
`
`Petitioner’s argument to the Board – that Cheng and Lewis taught or suggested the
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`claimed dosage forms, the recited Tmax, AUC0-24, and Cmax values were inherently
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`disclosed, and that a POSA therefore would have modified those teachings to
`
`arrive at the recited Tmax, AUC0-24, and Cmax values.
`
`In response to these rejections, Applicant explained that Cheng, Lewis, and
`
`the other cited references failed to teach or suggest the claimed range of mean Tmax
`
`values, or to provide any motivation that would lead the skilled person to a method
`
`that would provide those values. Applicant also amended the claims to recite
`
`particular limitations related to AUC0-24 and Cmax obtained following oral
`
`administration of a single dose. In addition, Patent Owner conducted an interview
`
`with the Examiner and his Supervisor on November 20, 2003, where “[i]t was
`
`agreed that the claims were allowable over the prior art previously relied upon by
`
`the Examiner,” including the Cheng, Timmins, and Lewis references. See
`
`Statement of Substance of Interview dated Nov. 25, 2003 at 2 (Ex. 1006 at 50-53).
`
`After considering Applicant’s arguments and amendments, the Examiner
`
`eventually withdrew the rejections based on Cheng, Timmins, and Lewis and
`
`allowed the claims of the ’625 application. Notice of Allowance for the ’625
`
`application mailed Feb. 11, 2004 (Ex. 1006 at 27). The ’459 patent then issued on
`
`September 14, 2004. See ’459 patent. In other words, none of the positions on
`
`which Petitioner now relies survived Applicant’s amendments and arguments
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`advanced during prosecution of the ’459 patent. The Patent Office thus correctly
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`concluded that the claims were patentable over Cheng, Timmins, Lewis, and a
`
`combination of prior art because the references failed to teach or suggest key
`
`limitations (e.g., a mean Tmax of 5.5 hours to 7.5 hours, a mean AUC0-24 of 22,590
`
`± 3,626 ng·hr/mL and mean Cmax of 2,435 ± 630 ng/mL on the first day of
`
`administration, and a mean AUC0-24 of 24,136 ± 7,996 ng·hr/mL and mean Cmax of
`
`2,288 ± 736 ng/mL on the 14th day of administration, for administration of a 2,000
`
`mg once-a-day dose of metformin) recited in the claims of the ’459 patent.
`
`D. Litigation Involving the ’459 Patent
`
`The ’459 patent is currently the subject of a pending action in the District of
`
`Delaware, Shionogi Inc. and Andrx Labs. L.L.C. v. Aurobindo Pharma Ltd. et al.,
`
`Civ. Act. No. 1:17-cv-00072-MSG (D. Del. Jan. 25, 2017). Patent Owner and
`
`Shionogi Inc. (“Shionogi”) (the exclusive licensee of the ’459 patent in the United
`
`States) filed a complaint on January 25, 2017, and the defendants filed an answer
`
`and counterclaims for declaratory judgment of noninfringement and invalidity on
`
`July 24, 2017. On September 13, Aurobindo filed a First Amended Answer and
`
`Affirmative Defenses and Counterclaims. Patent Owner and Shionogi filed an
`
`Answer and Defenses to Counterclaims on September 27.
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`The ’459 patent is also currently the subject of a second pending action in
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`
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`the District of Delaware, Shionogi Inc. et al. v. Qingdao Baheal Pharmaceutical
`
`Co. Ltd., Civ. Act. No. 17-cv-1347-MSG (D. Del. Sept. 22, 2017).
`
`The ’459 patent was previously the subject of a number of other actions:
`
` Sciele Pharma, Inc. et al v. Lupin Ltd. et al., No. 1-09-cv-00105 (D.
`
`Md.). This action was stayed and administratively closed on February
`
`20, 2009, prior to ruling on any claims of patent infringement or any
`
`defenses and counterclaims of patent invalidity following settlement
`
`and entry by the District of Delaware of a Stipulation and Order of
`
`Dismissal on June 13, 2013 in the earlier-filed Sciele Pharma, Inc. v.
`
`Lupin Ltd., Civ. Action No. 09-0037 (D. Del.) action.
`
` Takeda Pharmaceutical Company Limited et al v. Mylan, Inc. et al.,
`
`No. 1-12-cv-00024 (S.D.N.Y.), and Takeda Pharmaceutical Company
`
`Limited et al v. Mylan, Inc. et al., No. 1-12-cv-02038 (S.D.N.Y.).
`
`These consolidated actions were dismissed on February 26, 2014,
`
`before the final pre-trial conference.
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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` Takeda Pharmaceutical Co., Ltd., et. al. v. Mylan, Inc., et. al., No. 2-
`
`12-cv-00026 (W.D. Pa.), which was transferred to the S.D.N.Y. and
`
`later dismissed on February 26, 2014.
`
`E. Alleged Prior Art Relied on by Petitioner
`
`The Petition presents two invalidity grounds based on four references
`
`alleged to be prior art to the ’459 patent.
`
`Chen. International Patent Application Publication No. WO 00/12097
`
`(“Chen”) is titled “Controlled Release Tablet Comprising a Hypoglycemic Drug
`
`and an Antihyperglycemic Drug.”3 Chen discloses a controlled release
`
`pharmaceutical tablet containing an antihyperglycemic drug and a hypoglycemic
`
`drug. The disclosed formulation does not contain an expanding or gelling polymer
`
`layer and comprises a core containing the antihyperglycemic drug and the
`
`3 The issued United States counterpart of Chen (i.e., U.S. Patent No. 6,284,275)
`
`was considered by the Examiner during prosecution of the ’459 patent. See Form
`
`PTO-1449 included with Office Action mailed Dec. 31, 2001 for the ’625
`
`application (Ex. 1006 at 262); Form PTO-1449 included with Office Action mailed
`
`July 14, 2003 for the ’625 application (Ex. 1006 at 201). This reference also
`
`accordingly appears in the list of References Cited on the face of the ’459 patent.
`
`See ’459 patent.
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`hypoglycemic drug, a semipermeable coating membrane surrounding the core and
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`at least one passageway in the membrane to allow the drugs to be released from the
`
`core. Chen p. 1 (Ex. 1011).
`
`Chen lists the same inventive entity as the ’459 patent (i.e., Chih-Ming
`
`Chen, Xiu Xiu Cheng, Joseph Chou, and Steve Jan). Chen published on March 9,
`
`2000, less than one year prior to the November 3, 2000 filing date of the ’459
`
`patent.
`
`Cheng. International Patent Application Publication No. WO 99/47125
`
`(“Cheng”) is titled “Controlled Release Oral Tablet Having a Unitary Core.”
`
`Cheng discloses a “controlled release antihyperglycemic tablet … comprising a
`
`core containing the antihyperglycemic drug, a semipermeable membrane coating
`
`the core and at least one passageway in the membrane.” Cheng at Abstract.
`
`Cheng teaches mean peak plasma (i.e., Tmax) levels at 8-12 hours after oral
`
`administration following dinner. Thus, Cheng explicitly describes a formulation
`
`providing a mean Tmax that is longer than the mean Tmax required by the claims (i.e.,
`
`5.5 to 7.5 hours).
`
`As set forth above, Cheng was the subject of three office actions during the
`
`prosecution of the ’459 patent, serving as the basis for rejections under both pre-
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`AIA 35 U.S.C. §§ 102 and 103, all of which were overcome by Patent Owner
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`IPR2017-01673
`U.S. Patent No. 6,790,459
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`during prosecution. Cheng accordingly appears in the list of References Cited on
`
`the face of the ’459 patent.
`
`Timmins. International Patent Application Publication No. WO 99/47128
`
`(“Timmins”) is titled “Biphasic Controlled Release Delivery System for High
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`Solubility Pharmaceuticals and Method.” It was published on the same day as
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`Cheng. Timmins discloses a “biphasic controlled release delivery system for
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`pharmaceuticals which have high water solubility, such as the antidiabetic
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`metformin [hydrochloride] salt, … which provides a dosage form that has
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`prolonged gastric residence.” Timmins at Abstract.
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`Timmins does not disclose a single mean Tmax value for the disclosed
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`compositions. Specifically, Timmins does not teach a mean Tmax between 5.5 to
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`7.5 hours, as required by independent claim 1 of the ’459 patent. Timmins
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`provides no teaching at all on what range of mean Tmax values would be desirable.
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`Timmins was cited to and considered by the Examiner during the
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`prosecution of the ’459 patent, and accordingly appears in the list of References
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`Cited on the face of the ’459 patent. See Form PTO-1449 dated Jan. 28, 2004 for
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`the ’625 application (Ex. 1006 at 31); Form PTO-1449 included with Notice of
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`Allowance mailed Feb. 11, 2004 (Ex. 1006 at 35); ’459 patent.
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`Tucker. Tucker is an August 1981 article from the British Journal of
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`U.S. Patent No. 6,790,459
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`
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`Clinical Pharmacology titled “Metformin Kinetics in Healthy Subjects and in
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`Patients with Diabetes Mellitus.” Tucker discloses the results of studies on the
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`kinetics of metformin after intravenous and oral administration in four healthy
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`subjects and after oral administration to 12 patients with type 2 diabetes. Tucker at
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`235. Tucker discloses the administration of 0.5 g, 1.0 g, and 1.5 g oral doses of
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`metformin in the form of Glucophage® tablets. See Tucker at 236.
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`Tucker reports mean Tmax values for four different groups of patients
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`receiving 0.5 g, 1.0 g, 1.0 g, and 1.5 g oral doses of metformin of 2.2 ± 0.5 hours,
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`2.1 ± 0.8 hours, 2.4 ± 0.7 hours, and 1.5 ± 0.4 hours, respectively. Tucker at 240-
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`41. Thus, Tucker describes metformin dosage regimens providing a mean Tmax that
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`is shorter than the mean Tmax required by the claims (i.e., 5.5 to 7.5 hours).
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`Lewis. International Patent Application Publication No. WO 00/28989
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`(“Lewis”) is titled “Pharmaceutical Composition for Modified Release of an
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`Insulin Sensitiser and Another Antidiabetic Agent.” Lewis discloses a
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`pharmaceutical composition comprising “an insulin sensitiser and another
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`antidiabetic agent and a pharmaceutically acceptable carrier therefor, wherein the
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`composition is arranged to provide a modified release of at least one of the insulin
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`sensitiser and the other antidiabetes agent, and the use of such composition in
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`medicine.” Lewis at Abstract.
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`Lewis does not disclose a single mean Tmax value for the disclosed
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`compositions, let alone a mean Tmax between 5.5 to 7.5 hours, as required by
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`independent claim 1 of the ’459 patent. Nor does Lewis provide any teaching on
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`what range of mean Tmax values would be desirable. In fact, Lewis provides no in
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`vivo data whatsoever, or any indication what possible pharmacokinetic parameters
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`the disclosed formulations should display.
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`As set forth above, Lewis was the subject of two office actions during the
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`prosecution of the ’459 patent, serving as the basis for rejections under both pre-
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`AIA 35 U.S.C. §§ 102 and 103, all of which were overcome by Patent Owner
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`during prosecution. Lewis accordingly appears in the list of References Cited on
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`the face of the ’459 patent.
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`III. Level of Ordinary Skill in the Art
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`A person of ordinary skill in the art at the time of the invention would be a
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`person who, at the time of the invention, held a degree in pharmacy, chemistry,
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`chemical engineering, or a related field with at least three to five years of
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`pharmacokinetics, biopharmaceutics, medicinal chemistry, pre-formulation, or
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`formulation experience, research, or training. In addition, such a person would be
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`familiar, at the time of the invention, with the methods used in formulating oral
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`dosage forms, modified release dosage forms, and osmotic delivery, and have an
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`understanding of the fundamental principles as to how osmotic dosage forms
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`behave and function.
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`IV. Claim Construction
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`Patent Owner proposes the following constructions for the purposes of this
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`proceeding.4
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`A.
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`“Membrane”
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`The term “membrane” should be construed to mean “a membrane that is
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`permeable to both aqueous solutions or bodily fluids and to the active drug or
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`pharmaceutical ingredient[, and that] is porous to drug.” This proposed
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`construction encompasses the term “semipermeable membrane” as defined in the
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`’459 patent. Patent Owner’s proposed construction comes directly from the
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`express definition that the Applicant provided in the ’459 patent. See ’459 patent
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`col. 11 ll. 53-61. Under established claim construction principles, where the
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`inventors set forth an express definition of a claim term in the specification, that
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`4 Patent Owner reserves the right to pursue different constructions in other venues,
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`where different standards may be applicable.
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`definition governs. Sinorgchem Co. v. Int’l Trade Comm’n, 511 F.3d 1132, 1136
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`(Fed. Cir. 2007) (“[T]he inventor’s lexicography governs.”).
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`Petitioner’s proposed construction for the term “the membrane” is incorrect
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`and contrary to the express definition in the ’459 patent in two ways. First,
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`Petitioner’s proposed construction indicates that the term “membrane” means “a
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`semipermeable membrane.” Corrected Pet. at 22. This is incorrect, as the ’459
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`patent explicitly states that the term “membrane,” as defined in the specification,
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`“generically encompasses the term ‘semipermeable membrane’,” indicating that
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`the terms are not co-extensive. See ’459 patent col. 11 ll. 59-61 (emphasis added).
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`Thus, Petitioner’s construction which equates these terms cannot be correct.
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`Second, Petitioner’s proposed construction states that the term “membrane” means
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`a semipermeable membrane that is “impermeable to the active drug or
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`pharmaceutical ingredient ….” Corrected Pet. at 22 (emphasis added). This
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`assertion directly contradicts the definition in the ’459 patent, which states that
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`“membrane” means “a membrane that is permeable to both aqueous solution