IPR2017-01648
`U.S. Patent No. 6,866,866
`
`
`
`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 IPR2017-01648
`U.S. Patent No. 6,866,866
`____________________________________________
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`UNDER 37 C.F.R. § 42.107
`
`

`

`IPR2017-01648
`U.S. Patent No. 6,866,866
`
`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 ’866 Patent ..................................................................................... 7 
`D. 
`Litigation Involving the ’866 Patent ................................................... 10 
`E. 
`Alleged Prior Art Relied on by Petitioner ........................................... 12 
`III.  Level of Ordinary Skill in the Art ................................................................. 15 
`IV.  Claim Construction ........................................................................................ 16 
`A. 
`“Membrane” ........................................................................................ 16 
`B. 
`“Dinnertime” or “At Dinner” .............................................................. 18 
`C. 
`“Tmax” ................................................................................................... 18 
`D.  Other Claim Terms Not Requiring Construction ................................ 19 
`The Petition Fails to Establish a Reasonable Likelihood that Any of Claims
`1-25 is Anticipated by Chen (Ground I) ........................................................ 19 
`VI.  The Petition Fails to Establish a Reasonable Likelihood that Any of Claims
`1-3 is Anticipated by Timmins (Ground II) .................................................. 21 
`A.  Ground II Should Be Denied Because the Petition Does Not Apply the
`Correct Legal Standard for the Anticipation of a Claimed Range By
`an Overlapping Prior Art Range.......................................................... 21 
`1. 
`A Claim to a Range is Anticipated By a Prior Art Disclosure of
`an Overlapping Range Only Where There Is No Reasonable
`Difference in How the Invention Operates Over the Ranges ... 21 
`Petitioner Contends that Timmins Discloses a Range of Mean
`Tmax Values, Rather Than Specific Mean Tmax Values Within
`That Range ................................................................................ 22 
`Petitioner Fails to Sufficiently Show How the Range of Mean
`Tmax Values Allegedly Disclosed By Timmins Anticipates the
`Claimed Range .......................................................................... 24 
`Ground II Should Also Be Denied Because it Presents the Same Prior
`Art that Previously Was Considered and Rejected By the Patent
`Office ................................................................................................... 25 
`
`V. 
`
`B. 
`
`2. 
`
`3. 
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`VII.  The Petition Fails to Establish a Reasonable Likelihood that Any of Claims
`1-25 is Obvious Over Cheng in View of Timmins (Ground III) .................. 26 
`VIII.  Objective Indicia Support the Non-Obviousness of the Challenged
`Claims ............................................................................................................ 30 
`IX.  Conclusion ..................................................................................................... 33 
`
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Atofina v. Great Lakes Chemical Corp.,
`441 F.3d 991 (Fed. Cir. 2006) ............................................................ 4, 21, 22, 24
`ClearValue, Inc. v. Pearl River Polymers, Inc.,
`668 F.3d 1340 (Fed. Cir. 2012) ...................................................................... 4, 22
`INEOS USA LLC v. Berry Plastics Corp.,
`783 F.3d 865 (Fed. Cir. 2015) .................................................................. 3, 22, 24
`In re Cyclobenzaprine Hydrochloride Extended-Release Patent Litigation,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 27
`In re Katz,
`687 F.2d 450 (C.C.P.A. 1982) ............................................................................ 20
`Kinetic Technologies, Inc. v. Skyworks Solutions, Inc.,
`IPR2014-00529, Paper 8 (P.T.A.B. Sept. 23, 2014) ............................................. 5
`Sinorgchem Co. v. International Trade Commission,
`511 F.3d 1132 (Fed. Cir. 2007) .................................................................... 17, 18
`Tessera, Inc. v. Internatonal Trade Commission,
`646 F.3d 1357 (Fed. Cir. 2011) .......................................................................... 21
`Titanium Metals Corp. v. Banner,
`778 F.2d 775 (Fed. Cir. 1985) ............................................................................ 22
`Docketed Cases
`Sciele Pharma Inc. et al. v. Lupin Ltd., et al.,
`No. 2012-1228 (Fed. Cir.) .................................................................................. 11
`Sciele Pharma, Inc. et al v. Lupin Ltd. et al.,
`No. 1-09-cv-00105 (D. Md.) ............................................................................... 11
`Sciele Pharma, Inc. v. Lupin Ltd.,
`Civ. Act. No. 09-0037 (D. Del.) ......................................................................... 11
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`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
`Shionogi Inc. et al. v. Nostrum Laboratories, Inc., et al.,
`1:12-cv-04402 (D.N.J.) ....................................................................................... 12
`Shionogi Inc. et al. v. Qingdao Baheal Pharmaceutical Co. Ltd.,
`Civ. Act. No. 17-cv-1347-MSG (D. Del.) .......................................................... 11
`Shionogi Pharma v. Mylan, Inc.,
`Civ. Act. No. 10-135 (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.) ........................................................................... 12
`Takeda Pharmaceutical Company Limited et al v. Mylan, Inc. et al.,
`No. 1-12-cv-02038 (S.D.N.Y.) ........................................................................... 12
`Statutes, Codes & Regulations
`35 U.S.C. § 102(g) ................................................................................................... 20
`35 U.S.C. § 314 .......................................................................................................... 1
`37 C.F.R. § 42.108 ..................................................................................................... 1
`American Inventors Protection Act of 1999 ............................................................ 20
`Intellectual Property and High Technology Technical Amendments
`Act of 2002 ......................................................................................................... 20
`Other Authorities
`December 11, 2002 Examination Guidelines for 35 U.S.C. § 102(e) ..................... 20
`MPEP § 706.02(F)(1)(I)(C)(3) ........................................................................... 19, 20
`MPEP § 2132(III) ..................................................................................................... 20
`MPEP § 2136.04 ...................................................................................................... 20
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`
`I.
`
`Introduction
`
`Aurobindo petitions to institute inter partes review of U.S. Patent No.
`
`6,866,866 (“the ’866 patent”) (Ex. 1001) based on legally deficient grounds and on
`
`references already effectively considered and rejected by the Patent Office over the
`
`course of a rigorous examination. The Petition and the accompanying Declaration
`
`of Dr. Fatemeh Akhlaghi (Ex. 1019) not only reargue positions that the Patent
`
`Office previously considered and rejected before issuing the challenged claims, but
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`also (a) assert a reference that does not even qualify as prior art to the ’866 patent,
`
`and (b) rest on a conclusory allegation of anticipation that fails to apply the proper
`
`legal standard. 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 1-25 of the ’866 patent. The challenged
`
`claims describe the important discovery of controlled release once-a-day dosage
`
`forms of metformin that provide effective control of blood glucose levels and that
`
`are superior to prior dosage forms. More specifically, the challenged claims, inter
`
`alia, recite a controlled release oral dosage form for the reduction of serum glucose
`
`levels in human patients with non-insulin-dependent diabetes mellitus (“NIDDM,”
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`also known as type 2 diabetes), comprising an effective dose of metformin or a
`
`pharmaceutically acceptable salt thereof and a controlled-release carrier, wherein
`
`following oral administration of a single dose, the dosage form provides a mean
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`time to maximum plasma concentration (Tmax) of the metformin from 5.5 to 7.5
`
`hours after administration following dinner. ’866 patent, col. 21 ll. 48-59. The
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`claimed dosage form is embodied in Fortamet® Extended Release Tablets, Patent
`
`Owner’s antihyperglycemic drug product used in the management of type 2
`
`diabetes.
`
`The Petition asserts three invalidity grounds, none of which should be
`
`instituted.
`
`First, Petitioner asserts that claims 1-25 are anticipated by Chen (Ex. 1007)
`
`– a reference that does not even qualify as prior art to the ’866 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.
`
`
`1 See International Patent Application Publication No. WO 00/12097 (hereinafter
`
`“Chen” or Ex. 1007).
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`Second, Petitioner asserts that claims 1-3 are anticipated by Timmins (Ex.
`
`1003),2 which Petitioner states discloses a dosage form of metformin that provides
`
`a range of mean Tmax values. See Corrected Petition for Inter Partes Review filed
`
`July 18, 2017 (hereinafter “Corrected Pet.”) at 18. Petitioner states that this range
`
`“overlaps and intrudes into each of the ranges claimed by claims 1-3 of the ’866
`
`patent,” and concludes that these claims are therefore “taught in every detail by
`
`Timmins and are, therefore, anticipated by Timmins.” Id. However, Timmins
`
`does not disclose the claimed range. Instead, Petitioner relies on the disclosure of
`
`a median Tmax value without any information that would allow determination of a
`
`mean Tmax.
`
`Furthermore, Petitioner applies the wrong legal standard for anticipation of a
`
`claimed range by a reference that discloses an overlapping range, ignoring over a
`
`decade of Federal Circuit case law.
`
`In fact, the correct legal standard for overlapping ranges requires a showing
`
`that the prior art reference describes the claimed range with sufficient specificity
`
`such that a reasonable fact finder could conclude that there is no reasonable
`
`difference in how the invention operates over the ranges. See INEOS USA LLC v.
`
`2 See International Patent Application Publication No. WO 99/47128 (hereinafter
`
`“Timmins” or Ex. 1003).
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`Berry Plastics Corp., 783 F.3d 865, 869 (Fed. Cir. 2015) (citing Atofina v. Great
`
`Lakes Chem. Corp., 441 F.3d 991 (Fed. Cir. 2006); ClearValue, Inc. v. Pearl River
`
`Polymers, Inc., 668 F.3d 1340 (Fed. Cir. 2012)). Petitioner and its declarant fail
`
`even to offer any argument that there is no reasonable difference in how the
`
`invention operates over the claimed range and the range disclosed by Timmins. As
`
`a result, Petitioner also has failed to meet its burden of establishing a reasonable
`
`likelihood that it will prevail on at least one claim based on anticipation by
`
`Timmins, and Ground II should be denied.
`
`Third, Petitioner asserts that claims 1-25 are obvious over Cheng (Ex. 1002)
`
`in view of Timmins.3 However, Cheng and Timmins were already effectively
`
`considered and rejected by the Patent Office during prosecution of the application
`
`that issued as the ’866 patent. Moreover, 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 ’866 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. Accordingly, Petitioner also has failed to meet its
`
`burden of establishing a reasonable likelihood that it will prevail on at least one
`
`
`3 See International Patent Application Publication No. WO 99/47125 (hereinafter
`
`“Cheng” or Ex. 1002).
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`claim based on the combination presented in Ground III. Therefore, Ground III
`
`should be denied.
`
`Each of the Grounds in the Petition thus falls far short of providing the
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`“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 (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). ’866 patent, col. 1 ll. 56-57. At the time of filing of
`
`the ’866 patent in November 2000, metformin hydrochloride was marketed as
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`Glucophage® by Bristol-Myers Squibb in the United States. Id. col. 1 ll. 61-63.
`
`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. 63 – col. 2 l. 2. However, because
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`metformin is a short-acting drug, patients had to take the medication two or three
`
`times each day. Id. col. 2 ll. 4-6. Such frequent dosing typically led to reduced
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`patient compliance and increased adverse events. See id. col. 1 ll. 14-18; col. 2 ll.
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`4-6. In the case of metformin, such adverse events include the potentially
`
`dangerous side-effects of anorexia, nausea, and vomiting. Id. col. 2 ll. 6-8; col. 20
`
`ll. 16-18.
`
`At the time of the ’866 patent, there was thus a need in the art for 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.
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`B. Clinical Development and Approval of Fortamet®
`
`To address these shortcomings in the prior art treatments for type 2 diabetes,
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`the inventors of the ’866 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
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`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
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`type 2 diabetes on April 27, 2004. See Fortamet® FDA Approval Letter (Ex.
`
`2001).
`
`C. The ’866 Patent
`
`The ’866 Patent, entitled “Controlled Release Metformin Compositions,”
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`issued from U.S. Patent Application No. 09/705,630, filed on November 3, 2000
`
`(“the ’630 application”). The named inventors are Chih-Ming Chen, Xiu-Xiu
`
`Cheng, Steve Jan, and Joseph Chou.
`
`During prosecution of the ’630 application, the Patent Office was aware of,
`
`and specifically considered, Cheng (Ex. 1002), on which Petitioner now relies. As
`
`an initial matter, Applicant discussed both Timmins and Cheng in the Background
`
`of the Invention section of the ’866 patent specification. ’866 patent col. 2 ll. 34-
`
`47. In addition, in the first Office Action, the Examiner rejected the pending
`
`claims over Cheng under both pre-AIA 35 U.S.C. §§ 102 and 103, stating that
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`Cheng “discloses controlled metformin compositions” including those having “a
`
`semi-permeable membrane coating surrounding the core.” Office Action mailed
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`Dec. 31, 2001 for the ’630 application at 4, 6 (Ex. 1005 at 92, 94). 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 has the same composition taught by the specification as
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`providing the instant mean fluctuation indexes.” Office Action mailed Oct. 22,
`
`2002 for the ’630 application at 5 (Ex. 1005 at 126). Finally, in a third Office
`
`Action, the Examiner rejected the claims as allegedly obvious over Cheng, 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] with the motivation of providing
`
`controlled delivery of metformin over a desired period of time.” Office Action
`
`mailed May 21, 2003 for the ’630 application at 4 (Ex. 1005 at 152). The rationale
`
`underlying these rejections was the same as Petitioner’s argument to the Board –
`
`that Cheng taught or suggested the claimed dosage forms, and therefore the recited
`
`Tmax was inherently disclosed, or that a POSA would have modified those
`
`teachings to arrive at the recited Tmax.
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`In response to these rejections, Applicant explained that Cheng and the other
`
`cited references failed to teach or suggest the claimed range of mean Tmax values,
`
`or provide any motivation that would lead the skilled person to dosage forms
`
`providing those values. After considering Applicant’s arguments and amendments,
`
`the Examiner eventually withdrew the rejections based on Cheng. Notice of
`
`Allowance mailed Dec. 19, 2003 for the ’630 application at 1 (Ex. 1005 at 178);
`
`Form PTO-1449 dated Dec. 12, 2003 for the ’630 application (Ex. 1005 at 177);
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`Supplemental Notice of Allowability dated Nov. 30, 2004 at 1-2 (Ex. 1005 at 198-
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`99); see the ’866 patent.
`
`The Patent Office also considered United States Patent No. 6,475,521
`
`(hereinafter “the ’521 patent”), which had been previously cited to the Examiner
`
`by Patent Owner, and which accordingly appears as a Reference Cited on the face
`
`of the ’866 patent. Notice of Allowance mailed Dec. 19, 2003 for the ’630
`
`application at 1 (Ex. 1005 at 178); Form PTO-1449 dated Dec. 12, 2003 for the
`
`’630 application (Ex. 1005 at 177); Supplemental Notice of Allowability dated
`
`Nov. 30, 2004 at 1-2 (Ex. 1005 at 198-99).4
`
`
`4 The ’521 patent is a continuation-in-part of United States Patent Application No.
`
`09/044,446 to which Timmins also claims priority. Thus, the ’521 patent has
`
`essentially the same disclosure as Timmins, plus additional disclosure. For
`
`purposes of this dispute, the only meaningful difference in the disclosures of the
`
`’521 patent and Timmins is that Timmins discloses a method “for treating
`
`hyperglycemia including Type II diabetes (NIDDM) and/or Type I diabetes
`
`(IDDM) wherein a therapeutically effective amount of the biphasic formulatin
`
`[sic] of the invention containing metformin or a salt thereof, optionally in
`
`combination with another antihyperglycemic agent, is administered to a patient in
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`After considering Cheng, the ’521 patent, and the other prior art before the
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`Patent Office, the Examiner allowed the claims of the ’630 application. The ’866
`
`patent then issued on March 15, 2005. See ’866 patent. The Patent Office thus
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`correctly concluded that the claims were patentable over Cheng, Timmins, 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) recited in the claims of the
`
`’866 patent.
`
`D. Litigation Involving the ’866 Patent
`
`The ’866 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
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`Shionogi Inc. (“Shionogi”) (the exclusive licensee of the ’866 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
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`July 24, 2017. On September 13, Aurobindo filed a First Amended Answer and
`
`Affirmative Defenses and Counterclaims. Patent Owner and Shionogi filed an
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`Answer and Defenses to Counterclaims on September 27.
`
`
`need of treatment,” while the ’521 patent lacks this specific disclosure. See
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`Timmins p. 22 ll. 14-21; cf. ’521 patent.
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`The ’866 patent is also currently the subject of a second pending action in
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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. Sep. 22, 2017).
`
`The ’866 patent was previously the subject of a number of other actions:
`
` Sciele Pharma, Inc. v. Lupin Ltd., Civ. Act. No. 09-0037 (D. Del.) and
`
`Shionogi Pharma v. Mylan, Inc., Civ. Act. No. 10-135 (D. Del.),
`
`which were consolidated. In response to the district court’s grant of
`
`plaintiff’s motion for a preliminary injunction, the case was appealed
`
`to the Federal Circuit. Sciele Pharma Inc. et al. v. Lupin Ltd., et al.,
`
`No. 2012-1228 (Fed. Cir. July 2, 2012). A Federal Circuit panel
`
`issued an opinion on July 2, 2012, vacating the district court’s grant of
`
`a preliminary injunction, in the Sciele District of Delaware case, and
`
`remanding the case for further proceedings. Thereafter, the parties
`
`settled the actions, and the district court entered a Stipulation and
`
`Order of Dismissal on June 13, 2013, prior to ruling on any claims of
`
`patent infringement or any defenses and counterclaims of patent
`
`invalidity.
`
` Sciele Pharma, Inc. et al v. Lupin Ltd. et al., No. 1-09-cv-00105 (D.
`
`Md.). This was a second-filed action that was stayed and
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`administratively closed on February 20, 2009, prior to ruling on any
`
`claims of patent infringement or any defenses and counterclaims of
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`patent invalidity, following settlement of the aforementioned Sciele
`
`action in Delaware.
`
` 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.
`
` 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.
`
` Shionogi Inc. et al. v. Nostrum Laboratories, Inc., et al., 1:12-cv-
`
`04402 (D.N.J.). The parties settled prior to the defendants answering
`
`the complaint, and the court dismissed the case on May 3, 2013.
`
`E. Alleged Prior Art Relied on by Petitioner
`
`The Petition presents three invalidity grounds based on three references
`
`alleged to be prior art to the ’866 patent.
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`Chen. International Patent Application Publication No. WO 00/12097
`
`(“Chen”) is titled “Controlled Release Tablet Comprising a Hypoglycemic Drug
`
`and an Antihyperglycemic Drug.”5 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
`
`hypoglycemic drug, a semipermeable coating membrane surrounding the core and
`
`at least one passageway in the membrane to allow the drugs to be released from the
`
`core. Chen p. 1 (Ex. 1007).
`
`Chen lists the same inventive entity as the ’866 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 ’866
`
`patent.
`
`
`5 The issued United States counterpart of Chen (i.e., U.S. Patent No. 6,284,275, Ex.
`
`1015) was considered by the Examiner during prosecution of the ’866 patent.
`
`Office Action mailed Dec. 31, 2001 for the ’630 application (Ex. 1005 at 98). This
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`reference also accordingly appears in the list of References Cited on the face of the
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`’866 patent. See ’866 patent.
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`IPR2017-01648
`U.S. Patent No. 6,866,866
`Timmins. International Patent Application Publication No. WO 99/47128
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`(“Timmins”) is titled “Biphasic Controlled Release Delivery System for High
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`Solubility Pharmaceuticals and Method.” Timmins discloses a “biphasic
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`controlled release delivery system for pharmaceuticals which have high water
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`solubility, such as the antidiabetic metformin [hydrochloride] salt, … which
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`provides a dosage form that has prolonged gastric residence.” Timmins at
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`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 ’866 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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`A United States counterpart of Timmins (the ’521 patent) was cited to and
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`considered by the Examiner during the prosecution of the ’866 patent, and
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`accordingly appear as a Reference Cited on the face of the ’866 patent. Notice of
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`Allowance mailed Dec. 19, 2003 for the ’630 application at 1 (Ex. 1005 at 178);
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`Form PTO-1449 dated Dec. 12, 2003 for the ’630 application (Ex. 1005 at 177);
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`Supplemental Notice of Allowability dated Nov. 30, 2004 at 1-2 (Ex. 1005 at 198-
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`99). The disclosure related to mean Tmax values in the ’521 patent is the same as
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`that in Timmins.
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`

`

`IPR2017-01648
`U.S. Patent No. 6,866,866
`Cheng. International Patent Application Publication No. WO 99/47125
`
`(“Cheng”) is titled “Controlled Release Oral Tablet Having a Unitary Core.”
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`Cheng discloses a “controlled release antihyperglycemic tablet … comprising a
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`core containing the antihyperglycemic drug, a semipermeable membrane coating
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`the core and at least one passageway in the membrane.” Cheng at Abstract. It was
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`published on the same day as Timmins.
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`Cheng teaches mean peak plasma (i.e., Tmax) levels at 8-12 hours after oral
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`administration following dinner. Thus, Cheng explicitly describes a formulation
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`providing a mean Tmax that is longer than the mean Tmax required by the claims (i.e.,
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`5.5 to 7.5 hours).
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`As set forth above, Cheng was the subject of three office actions during the
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`prosecution of the ’866 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. Cheng accordingly appears as a Reference Cited on the face of
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`the ’866 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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`IPR2017-01648
`U.S. Patent No. 6,866,866
`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.6
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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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`’866 patent. Patent Owner’s proposed construction comes directly from the
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`express definition that the Applicant provided in the ’866 patent. See ’866 patent
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`col. 11 ll. 53-61. Under established claim construction principles, where the
`
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`6 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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`IPR2017-01648
`U.S. Patent No. 6,866,866
`inventors set forth an express definition of a claim term in the specification, that
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`definition governs. See Sinorgchem Co. v. Int’l Trade Comm’n, 511 F.3d 1132,
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`1136 (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 ’866 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 25. This is incorrect, as the ’866
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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 ’866 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 25 (emphasis added). This
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`assertion directly contradicts the definition in the ’866 patent, which states that
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`“membrane” means “a membrane that is permeable to both aqueous solutions or
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`bodily fluids and to the active drug or pharmaceutical ingredient ….” See ’866
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`patent col. 11 ll. 53-56 (emphasis added). Moreover, the ’866 patent states that
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`“the membr