`
`IPR2018-00530
`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 IPR2018-00530
`U.S. Patent No. 6,790,459
`____________________________________________
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`UNDER 37 C.F.R. § 42.107
`
`

`

`
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`I. 
`II. 
`
`TABLE OF CONTENTS
`
`Introduction .................................................................................................... 1 
`Background .................................................................................................... 7 
`A. 
`State of the Art in November 2000 ....................................................... 7 
`B. 
`Clinical Development and Approval of Fortamet® .............................. 8 
`C. 
`The ’459 Patent ..................................................................................... 9 
`D. 
`Litigation Involving the ’459 Patent ................................................... 13 
`E. 
`Alleged Prior Art Relied on by Petitioner ........................................... 17 
`III.  Level of Ordinary Skill in the Art .............................................................. 23 
`IV.  Claim Construction ..................................................................................... 23 
`A. 
`“Cmax” ................................................................................................... 24 
`B. 
`“Tmax” ................................................................................................... 24 
`C. 
`“AUC0-24” or “AUC0-24hr” .................................................................... 25 
`D.  Other Claim Terms Not Requiring Construction ................................ 25 
`Institution Should Be Denied Under 35 U.S.C. §§ 314(a) and 325(d)
`Because the Petitioner’s Request Provides Nothing New Over Its
`Previous Request for Inter Partes Review ................................................. 26 
`A. 
`Institution Should Be Denied Under § 325(d) Because Petitioner
`Presents Substantially The Same Prior Art And Arguments Previously
`Presented To (and Rejected by) The Office ........................................ 26 
`The General Plastic Factors Strongly Favor Denial of Institution
`Under 35 U.S.C. § 314(a) .................................................................... 27 
`VI.  The Petition Fails to Establish a Reasonable Likelihood that Any of
`Claims 1-21 is Obvious Over Cheng in View of Timmins, Wagner,
`Lewis, Gibaldi, and DeFronzo (Ground I) ................................................ 33 
`A. 
`Petitioner’s Conclusory Assertions Cannot Support a Finding of
`Motivation to Combine with a Reasonable Expectation of Success ... 33 
`Petitioner And Its Declaration Fail to Properly Assert a Reasonable
`Expectation of Success ........................................................................ 44 
`VII.  Objective Indicia Support the Non-Obviousness of the Challenged
`Claims ........................................................................................................... 45 
`VIII.  Patent Owner Reserves the Right to Challenge the Validity of This Inter
`Partes Review Proceeding ........................................................................... 48 
`IX.  Conclusion .................................................................................................... 48 
`
`V. 
`
`B. 
`
`B. 
`
`- i -
`
`

`

`TABLE OF AUTHORITIES
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`
`
`Page(s)
`
`
`
`Cases
`
`Ashland Oil, Inc. v. Delta Resins & Refractories, Inc.,
`776 F.2d 281 (Fed. Cir. 1985)............................................................................................35, 40
`
`Aurobindo Pharma,
`IPR2017-01673, Papers 1, 10 and 11 (PTAB) .........................................................2, 12, 27, 38
`
`Eli Lilly & Co. v. Medtronic, Inc.
`496 US 661 (1990) .............................................................................................................15, 16
`General Plastic Indus. v. Canon Kabushiki Kaisha,
`IPR2016-01357/-01358/-01359/-01360/-01361 (PTAB) ................................................ passim
`
`Intendis GMBH v. Glenmark Pharm. Inc., USA,
`822 F.3d 1355 (Fed. Cir. 2016)....................................................................................32, 42, 43
`
`InTouch Techs. v. VGO Commc’ns, Inc.,
`751 F.3d 1327 (Fed. Cir. 2014)..........................................................................................32, 42
`
`Kinetic Techs., Inc. v. Skyworks Sols., Inc.,
`IPR2014-00529, Paper 8 (PTAB Sept. 23, 2014) ......................................................................7
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................................................2
`
`In re NuVasive, Inc.,
`842 F.3d 1376 (Fed. Cir. 2016)....................................................................................32, 40, 41
`
`In re Van Os,
`844 F.3d 1359 (Fed. Cir. 2017)....................................................................................32, 40, 41
`
`NVIDIA Corp. v. Samsung Elec. Co.,
`IPR2016-00134, Paper 9 (PTAB May 4, 2016) .................................................................25, 29
`
`Oil States Energy Servs., LLC v. Greene’s Energy Group, LLC
`584 U. S. ___ (2018) (slip op., ) ..............................................................................................46
`
`Pers. Web Techs., LLC v. Apple, Inc.,
`848 F.3d 987 (Fed. Cir. 2017)............................................................................................32, 42
`
`Plas-Pak Indus., Inc. v. Sulzer Mixpac AG,
`600 F. App’x 755 (Fed. Cir. 2015) ....................................................................................32, 35
`
`- ii -
`
`

`

`
`Sciele Pharma, Inc. et al v. Lupin Ltd. et al.,
`No. 1-09-cv-00105 (D. Md.) ....................................................................................................14
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`Sciele Pharma, Inc. v. Lupin Ltd.,
`684 F.3d 1253 (Fed. Cir. 2012)................................................................................................36
`
`Sciele Pharma, Inc. v. Lupin Ltd.,
`No. 09-0037 (D. Del.) ..............................................................................................................14
`
`Shionogi Inc. and Andrx Labs. L.L.C. v. Aurobindo Pharma Ltd. et al.,
`No. 1:17-cv-00072-MSG (D. Del. Jan. 25, 2017) ...................................................................13
`
`Shionogi Inc. et al. v. Qingdao Baheal Pharmaceutical Co. Ltd.,
`No. 17-cv-1347-MSG (D. Del. Sept. 22, 2017) .......................................................................14
`
`Sinorgchem Co. v. Int’l Trade Comm’n,
`511 F.3d 1132 (Fed. Cir. 2007)..........................................................................................22, 23
`
`Takeda Pharmaceutical Co., Ltd., et. al. v. Mylan, Inc., et. al.,
`No. 2-12-cv-00026 (W.D. Pa.) .................................................................................................15
`
`Takeda Pharmaceutical Company Limited et al v. Mylan, Inc. et al.,
`No. 1-12-cv-00024 (S.D.N.Y.) ................................................................................................14
`
`Takeda Pharmaceutical Company Limited et al v. Mylan, Inc. et al.,
`No. 1-12-cv-02038 (S.D.N.Y.) ................................................................................................14
`
`Unified Patents Inc. v. Berman,
`No. IPR2016-01571, Paper 10 (PTAB December 14, 2016) ...................................................25
`
`In re Van Os,
`844 F.3d 1359 (Fed. Cir. 2017)....................................................................................32, 40, 41
`
`Federal Statutes
`
`35 U.S.C. § 102 ..................................................................................................................10, 16, 19
`
`35 U.S.C. § 103 ..................................................................................................................10, 16, 19
`
`35 U.S.C. § 314 ...................................................................................................................... passim
`
`35 U.S.C. § 316(a)(11) ...................................................................................................................30
`
`35 U.S.C. § 325(d) ...................................................................................................2, 14, 24, 25, 31
`
`Regulations
`
`37 C.F.R. § 42.24(d) ......................................................................................................................48
`
`- iii -
`
`

`

`
`37 C.F.R. § 42.100(b) ....................................................................................................................21
`37 CPR. § 42.100(b) ....................................................................................................................21
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`US. Patent No. 6,790,459
`
`IPR2018-0053O
`
`37 C.F.R. § 42.108 .....................................................................................................................3, 25
`37 CPR. § 42.108 ..................................................................................................................... 3, 25
`
`
`
`- iv -
`
`-iv-
`
`

`

`
`I.
`
`Introduction
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`In a transparent attempt at a second bite at the apple, Petitioner Aurobindo
`
`submits an equally deficient second petition attempting to institute inter partes
`
`review (“IPR”) of U.S. Patent No. 6,760,459 (“the ’459 patent”) (Ex. 1001) using
`
`the same three core references (including the same primary reference) that the
`
`Board previously found insufficient for institution. In fact, Petitioner merely
`
`modifies its prior case using the prior Decision Denying Institution by removing
`
`one secondary reference and adding three new secondary references, only one of
`
`which even relates to the drug recited in the claimed method, and one of which
`
`does not even qualify as prior art based on its indicated date of publication. But it
`
`is not merely the use of the same references that renders this second petition
`
`deficient. Petitioner only minimally adjusts the argument and declaration of its
`
`purported expert submitted with its first petition without addressing the
`
`fundamental reason for the denial of institution of its first petition – failure to
`
`adequately articulate a reason why a person of ordinary skill in the art (“POSA”) in
`
`November 2000 would have modified the references to achieve the claimed
`
`method.
`
`Specifically, in its prior Decision on Institution, the Board found that
`
`“Petitioner [did] not persuasively explain why a person of ordinary skill in the art
`
`- 1 -
`
`

`

`
`would have been motivated to modify Cheng to obtain the Tmax, AUC, and Cmax
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`values recited in the claims,” and instead had simply stated that a POSA could
`
`modify the alleged disclosure of Cheng to arrive at the alleged Tmax, AUC, and
`
`mean Cmax values recited in the claims of the ’459 patent. Aurobindo Pharma USA
`
`Inc. v. Andrx Labs, LLC, No. IPR2017-01673, Paper 11 at 14 (PTAB December
`
`29, 2017) (Ex. 2003). As in its first attempt, Petitioner has again failed to provide
`
`“some articulated reasoning with some rational underpinning to support the legal
`
`conclusion of obviousness.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418
`
`(2007).
`
`Because substantially the same prior art and arguments were previously
`
`presented to, and rejected by, the United States Patent and Trademark Office, the
`
`Board should exercise its discretion under 35 U.S.C. § 325(d) and reject this
`
`petition.
`
`Even should the Board decline to use its discretion to deny institution under
`
`35 U.S.C. § 325(d), it should deny institution under 35 U.S.C. § 314(a) because
`
`Petitioner’s allegations rest on a legally deficient ground that includes a reference
`
`indicating that it was published seven years after the filing date of the ’459 patent.
`
`As in its first attempt, this Petition and the accompanying Declaration of Dr.
`
`Fatemeh Akhlaghi (hereinafter “the Akhlaghi Declaration”) (Ex. 1009) reargue
`
`- 2 -
`
`

`

`
`positions that the Patent Office previously considered and rejected before issuing
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`the challenged claims in 2004, and subsequently denying institution Petitioner’s
`
`prior request for IPR in 2017. In short, Aurobindo is presenting the substantially
`
`the same arguments before the Office for the third time. 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. This is
`
`especially the case where, as here, the seven factors set forth by the Board for
`
`assessing whether follow-on petitions should be instituted either weigh in favor of
`
`a denial of institution or are neutral. See General Plastic Indus. v. Canon
`
`Kabushiki Kaisha, IPR2016-01357/-01358/-01359/-01360/-01361, Paper 19 at 9-
`
`10 (PTAB Sept. 6, 2017) (Decision Denying Request for Rehearing) (designated
`
`precedential) (hereinafter “General Plastic”).
`
`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
`
`- 3 -
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`

`

`
`alia, a method for lowering blood glucose levels in human patients needing
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`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`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 ngꞏhr/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 ngꞏhr/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.
`
`- 4 -
`
`

`

`The Petition asserts a single ground of invalidity – namely, that claims 1-21
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`
`
`are obvious over Cheng (Ex. 1002) in view of Timmins (Ex. 1013), Wagner (Ex.
`
`1019), Lewis (Ex. 1003), Gibaldi (Ex. 1018), and DeFronzo (Ex. 1020).1
`
`However, this ground of invalidity raises no new issues of patentability that were
`
`not previously considered by the Office during prosecution or Aurobindo’s first
`
`petition. The Office considered and rejected the Cheng, Timmins, and Lewis
`
`references during the lengthy prosecution of the application that issued as the ’459
`
`patent over the course of an examination that included three Office Actions.
`
`Petitioner raised these references yet again in its first petition, and this Board
`
`refused to institute IPR proceedings. Aurobindo has offered no new evidence or
`
`
`1 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); John G. Wagner, Fundamentals of
`
`Clinical Pharmacokinetics, 133-145 ( 1st ed. 1975) (hereinafter “Wagner” or Ex.
`
`1019); International Patent Application Publication No. WO 00/28989 (hereinafter
`
`“Lewis” or Ex. 1003); Milo Gibaldi & Donald Perrier, Pharmacokinetics, 2d ed.
`
`(hereinafter “Gibaldi” or Ex. 1018); Ralph A. DeFronzo, et al. Efficacy of
`
`Metformin in Patients with Non-Insulin-Dependent Diabetes Mellitus, 333 New
`
`Eng. J. Med. 541, (1995) (hereinafter “DeFronzo” or Ex. 1020).
`
`- 5 -
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`

`

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`arguments regarding these references that are fundamental to its sole ground of
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`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`invalidity.
`
`Petitioner cites three secondary references not previously considered by the
`
`Patent Office: Wagner, Gibaldi, and DeFronzo. But Aurobindo does not provide
`
`any rationale as to how these references overcome the deficiencies of the primary
`
`references in its first petition. Only one of these references (DeFronzo) relates to
`
`metformin, and one (Gibaldi) does not even qualify as prior art to the challenged
`
`claims based on its stated publication date. Petitioner cites to Wagner and Gibaldi
`
`for the proposition that a POSA could estimate multiple dose blood levels at a
`
`desired sampling time, and cites to DeFronzo for teaching the safety and efficacy
`
`of a 2,550 mg immediate release dosage form of metformin. However, beyond
`
`mere conclusory assertions, neither the Petition nor the Akhlaghi Declaration
`
`explain how these secondary references overcome the deficiencies of Cheng,
`
`Timmins, and Lewis previously found by the Patent Office and the Board. Even
`
`taking the arguments in the Petition at face value, Petitioner fails to show that a
`
`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 methods. In fact, the Petition never even states that a POSA would
`
`make such a combination in a way that would provide the AUC and Cmax
`
`- 6 -
`
`

`

`
`parameters recited in the challenged claims (let alone a reason why they would do
`
`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`so), or that they would have a reasonable expectation of success in doing so. For
`
`these reasons, Petitioner has again 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 I.
`
`The sole Ground in the Petition thus falls far short of providing the
`
`“articulated reasoning with rational underpinning” necessary to support a legal
`
`conclusion of anticipation or obviousness. Kinetic Techs., Inc. v. Skyworks Sols.,
`
`Inc., IPR2014-00529, Paper 8 at 16 (PTAB Sept. 23, 2014) (quoting In re Kahn,
`
`441 F.3d 977, 988 (Fed. Cir. 2006). Petitioner has not established a reasonable
`
`likelihood of prevailing on its obviousness ground. Accordingly, the Board should
`
`deny institution of inter partes review.
`
`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 that time, there was no fixed dosage regimen for Glucophage® to manage
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`- 7 -
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`

`

`
`hyperglycemia in patients with diabetes mellitus – instead, dosages were
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`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
`
`dangerous side-effects of anorexia, nausea, and vomiting. Id. col. 2 ll. 7-9; col. 20
`
`ll. 47-49.
`
`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
`
`- 8 -
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`

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`Fortamet® was comparable to immediate-release metformin in terms of efficacy
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`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).
`
`C. The ’459 Patent
`
`The ’459 Patent, entitled “Methods For Treating Diabetes Via
`
`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
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`- 9 -
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`

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`under pre-AIA 35 U.S.C. § 102, and over either Cheng or Lewis alone or in
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`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, (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.” (Ex. 1006 at 256). The Examiner
`
`again rejected the claims as allegedly anticipated by Cheng in the second Office
`
`Action, reiterating that Cheng “discloses controlled release 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, (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, (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
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`of the invention to manipulate the release profile of [Cheng] in accordance with the
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`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.” (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 claimed dosage forms,
`
`the recited Tmax, AUC0-24, and mean Cmax values were inherently disclosed, and that
`
`a POSA therefore would have modified those teachings to arrive at the recited
`
`Tmax, AUC0-24, and mean 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
`
`- 11 -
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`the Examiner,” including the Cheng, Timmins, and Lewis references. See
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`IPR2018-00530
`U.S. Patent No. 6,790,459
`
`Statement of Substance of Interview dated Nov. 25, 2003 (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
`
`advanced during prosecution of the ’459 patent. The Patent Office thus correctly
`
`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 ngꞏhr/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 ngꞏhr/mL and mean Cmax of
`
`2,288 ± 736 ng/mL on the 14th day of administration, for administration of a 2,000
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`mg once-a-day dose of metformin) recited in the claims of the ’459 patent.
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`Petitioner Aurobindo initially filed a petition requesting IPR of the ’459
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`patent in IPR2017-01673 on June 23, 2017. Aurobindo Pharma, IPR2017-01673,
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`Paper 1 (PTAB June 23, 2017). On December 29, 2017, the Board issued an order
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`denying institution. Ex. 2003.
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`D. Litigation Involving the ’459 Patent
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`The ’459 patent is currently the subject of two pending Hatch-Waxman
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`actions. One such action is pending in the District of Delaware, Shionogi Inc. and
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`Andrx Labs. L.L.C. v. Aurobindo Pharma Ltd. et al., Civ. Act. No. 1:17-cv-00072-
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`MSG (D. Del. Jan. 25, 2017). Patent Owner and Shionogi Inc. (“Shionogi”) (the
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`exclusive licensee of the ’459 patent in the United States) filed a complaint on
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`January 25, 2017, and the defendants filed an answer and counterclaims for
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`declaratory judgment of noninfringement and invalidity on July 24, 2017. On
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`September 13, 2017, Aurobindo filed a First Amended Answer and Affirmative
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`Defenses and Counterclaims. Patent Owner and Shionogi filed an Answer and
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`Defenses to Counterclaims on September 27, 2017. On May 23, 2018, Patent
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`Owner and Shionogi filed a Motion to Enforce Settlement Agreement. That
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`motion is not yet fully briefed.2
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`2 In that motion, Patent Owner and Shionogi contend that, as of April 27, 2018, the
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`parties agreed to the terms of a fully enforceable settlement agreement, a
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`settlement that would include withdrawal of Aurobindo’s Petition. Until that
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`The ’459 patent is also currently the subject of a second pending Hatch-
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`
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`Waxman action in the District of Delaware, Shionogi Inc. et al. v. Qingdao Baheal
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`Pharmaceutical Co. Ltd., No. 17-cv-1347-MSG (D. Del. Sept. 22, 2017).
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`Pursuant to 35 U.S.C. §§ 314(a) and/or 325(d), the Board and Director
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`should exercise their discretion to not institute this Petition as being duplicative of
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`currently pending patent litigation under the 21 U.S.C. § 355 (the “Hatch-Waxman
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`Act”). In particular, the Board and/or Director should deny and/or choose not to
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`institute this Petition, which represents an attempt to circumvent Congress’ intent
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`to allow for resolution of patent disputes over generic drugs through the framework
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`set forth in the Hatch-Waxman Act. Congress passed the Hatch-Waxman Act to
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`shorten the time and effort necessary for generic manufacturers to obtain marketing
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`approval. To obtain the shortened regulatory approval track provided by the Act,
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`generic manufacturers must file an Abbreviated New Drug Application (“ANDA”)
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`establishing bioequivalence of the generic drug to the innovator drug. See 21
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`U.S.C. § 355(j)(2). The generic manufacturer must also assert that any patents
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`listed in the FDA’s Orange Book as covering the innovator drug will not be
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`infringed and/or are invalid. Under the Hatch-Waxman, this filing is a constructive
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`motion is resolved by the District Court, however, Patent Owner and Shionogi are
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`obligated to respond to that Petition.
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`act of infringement allowing for the innovator to bring an infringement action
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`against the generic manufacturer. See id. Congress’ intent was to establish this
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`expedited infringement remedy for innovators in exchange for generic
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`manufacturers rights under the provisions of the Hatch-Waxman Act to avoid
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`costly and time-consuming studies required for approval of pioneer drugs. See Eli
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`Lilly & Co. v. Medtronic, Inc., 496 US 661, 676-67 (1990). For those parties that
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`take advantage of this abbreviated ANDA review system, Hatch-Waxman was
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`intended to be the sole mechanism for the resolution of patent disputes for Orange
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`Book listed patents.
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`Here, Aurobindo has availed itself of the provisions of the Hatch-Waxman
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`Act to shorten its development time and reduce its costs, and thus is bound by the
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`patent dispute resolution mechanism it chose. However, Aurobindo now seeks to
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`avoid the provisions of the Hatch-Waxman Act that allow for the Patent Owner to
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`assert infringement against Aurobindo. Congress established the Hatch-Waxman
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`Act to provide the mechanism of handling disputes for a narrow class of patents –
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`such as the one at issue in Petitioner’s second petition. Id. Petitioner’s strategy is
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`to gain the advantages afforded to generic manufacturers by Congress, while
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`avoiding the balancing of those advantages with the rights of innovators.
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`Congress’ intent was clearly to afford generic manufacturers the right to obtain
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`shortened regulatory approval, but only if innovators had the right to pursue
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`IPR2018-00530
`U.S. Patent No. 6,790,459
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`infringement and have the validity and infringement of the patents heard in Federal
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`court. Nothing in the AIA subverts this intent. For this reason alone, the petition
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`should be denied. See
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`The ’459 patent was previously the subject of a number of other actions:
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` Sciele Pharma, Inc. et al v. Lupin Ltd. et al., No. 1-09-cv-00105 (D.
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`Md.). This action was stayed and administratively closed on February
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`20, 2009, prior to ruling on any claims of patent infringement or any
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`defenses and counterclaims of patent invalidity following settlement
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`and entry by th