UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`RANBAXY LABORATORIES LTD and RANBAXY INC.,
`Petitioners
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`v.
`
`ADAMAS PHARMACEUTICALS, INC.,
`Patent Owner
`
`
`
`
`Inter Partes Review No.: 2015-00410
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`U.S. Patent No. 8,362,085
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`
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`
`
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT 8,362,085 UNDER
`35 U.S.C. §§ 311-319 AND 37 C.F.R. § 42
`
`

`
`
`
`TABLE OF CONTENTS
`TABLE OF CONTENTS .................................................................................................... ii
`
`TABLE OF CONTENTS .................................................................................................. .. ii
`
`TABLE OF CONTENTS
`
`LIST OF EXHIBITS ........................................................................................................... .. v
`
`LIST OF EXHIBITS ............................................................................................................. v
`
`I.
`
`I.
`
`MANDATORY NOTICES .................................................................................... .. 1
`
`MANDATORY NOTICES ...................................................................................... 1
`
`A.
`A.
`
`B.
`B.
`
`C.
`C.
`
`D.
`D.
`
`Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) ............................................ 1
`Real Party—In—Interest (37 C.F.R. § 42.8(b)(1)) .......................................... .. 1
`
`Related Matters (37 C.F.R. § 42.8(b)(2)) ....................................................... 2
`Related Matters (37 C.F.R. § 42.8(b)(2)) ..................................................... .. 2
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3))....................................... 2
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) ..................................... .. 2
`
`Service Information (37 C.F.R. § 42.8(b)(4)) ............................................... 2
`Service Information (37 C.F.R. § 42.8(b)(4)) ............................................. .. 2
`
`II.
`
`II. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT ......... 3
`
`GROUNDS FOR STANDING AND PROCEDURAL STATEMENT ....... .. 3
`
`III.
`
`III.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF
`THE PRECISE RELIEF REQUESTED ............................................................... 3
`THE PRECISE RELIEF REQUESTED ............................................................. .. 3
`
`IV. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW .............. 3
`IV.
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............ .. 3
`
`V.
`V.
`
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED ................ 4
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED .............. .. 4
`
`A. Grounds of Unpatentability ........................................................................... 4
`A.
`Grounds of Unpatentability ......................................................................... .. 4
`
`B. Overview of the ’085 Patent .......................................................................... 4
`
`Overview of the ’085 Patent ........................................................................ .. 4
`
`B.
`
`C.
`C.
`
`D.
`D.
`
`E.
`E.
`
`F.
`
`F.
`
`G.
`
`G.
`
`Prosecution Background ................................................................................ 5
`Prosecution Background .............................................................................. .. 5
`
`Priority Date of the ’085 Patent ..................................................................... 6
`Priority Date of the ’085 Patent................................................................... .. 6
`
`Level of Ordinary Skill in the Art .................................................................. 9
`Level of Ordinary Skill in the Art ................................................................ .. 9
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`Claim Construction ....................................................................................... .. 9
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`Claim Construction ......................................................................................... 9
`
`Patents and Printed Publications Relied On ............................................ .. 10
`
`Patents and Printed Publications Relied On .............................................. 10
`
`1.
`1.
`
`2.
`2.
`
`3.
`3.
`
`Rastogi – U.S. Patent No. 8,039,009 (Ex. 1007) ............................ 10
`Rastogi — U.S. Patent No. 8,039,009
`1007) .......................... .. 10
`
`Nürnberg – U.S. Patent No. 5,382,601 (Ex. 1009) ........................ 13
`Nurnberg — U.S. Patent No. 5,382,601
`1009) ...................... .. 13
`
`Ditzler (Ex. 1010) .............................................................................. 14
`Ditzler
`1010) ............................................................................ .. 14
`
`ii
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`

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`
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`4.
`
`5.
`
`’741 PCT – PCT International Publication No. WO
`2004/012741 (Ex. 1011) ................................................................... 15
`
`Namenda 2003 Label (Ex. 1014) ..................................................... 17
`
`H. Ground 1: Claims 1 and 7 are Anticipated by Rastogi ............................ 17
`
`1.
`
`Claim 1 is Anticipated by Rastogi .................................................... 17
`
`a)
`
`b)
`
`c)
`
`d)
`
`e)
`
`f)
`
`Rastogi Discloses Element (1) .............................................. 19
`
`Rastogi Discloses Element (2) .............................................. 19
`
`Rastogi Discloses Element (3) .............................................. 19
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`Rastogi Discloses Element (4) .............................................. 20
`
`Rastogi Discloses Element (5) .............................................. 21
`
`Rastogi Discloses Element (6) .............................................. 27
`
`2.
`
`Claim 7 is Anticipated by Rastogi .................................................... 29
`
`I.
`
`Ground 2: Claims 1-12 Would Have Been Obvious Over
`Nürnberg in View of Ditzler, the ’741 PCT and the Namenda
`2003 Label ...................................................................................................... 30
`
`1.
`
`Claim 1 ................................................................................................ 30
`
`a)
`
`b)
`
`One of Ordinary Skill in the Art Would Have Been
`Motivated to Make the Subject Matter of Claim 1,
`With a Reasonable Expectation of Success......................... 30
`
`Applicants’ Arguments Regarding Lack of
`Motivation Should Again Be Rejected ................................. 41
`
`Claim 7 ................................................................................................ 44
`
`Dependent Claims ............................................................................. 45
`
`Secondary Considerations Do Not Rebut the Strong
`Showing of Obviousness Here......................................................... 46
`
`Ground 2 Has Not Been Previously Considered .......................... 51
`
`2.
`
`3.
`
`4.
`
`5.
`
`iii
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`

`
`
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`J. Ground 3: Claims 1-12 Would Have Been Obvious Over the ’741 PCT
`in View of Ditzler and the Namenda 2003 Label...................................... 52
`
`K. Ground 4: Claims 1–12 Would Have Been Obvious Over Rastogi
`in View of Ditzler and the ’741 PCT .......................................................... 55
`
`1.
`
`2.
`
`Claims 1 and 7 .................................................................................... 55
`
`Dependent Claims ............................................................................. 57
`
`a)
`
`b)
`
`c)
`
`Element Added By Claims 2, 4, 6, 8, 10, and 12 ................ 57
`
`Elements Added By Claims 3, 5, 9 and 11 .......................... 58
`
`The Dependent Claims Would Have Been Obvious ......... 59
`
`VI. CONCLUSION ........................................................................................................ 60
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`
`
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`
`iv
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`

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`
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`
`
`Petitioners’
`Ex. No.
`Ex. 1001
`
`LIST OF EXHIBITS
`
`Description
`
`U.S. Patent No. 8,362,085, titled “Method for Administering an
`NMDA Receptor Antagonist to a Subject,” issued January 29, 2013
`Ex. 1002 Declaration of Arthur H. Kibbe, Ph.D.
`Ex. 1003
`Excerpt from the Prosecution History of U.S. Patent No. 8,362,085,
`June 25, 2012 Declaration of Dr. Gregory T. Went
`Excerpt from the Prosecution History of U.S. Patent No. 8,362,085,
`September 24, 2012 Notice of Allowance
`Provisional Application No. 60/630,885, filed November 23, 2004
`Provisional Application No. 60/635,365, filed December 10, 2004
`U.S. Patent No. 8,039,009, titled “Modified Release Formulations of
`Memantine Oral Dosage Forms,” issued on October 18, 2011
`Provisional Application No. 60/581,242, filed on June 17, 2004
`U.S. Patent 5,382,601, titled “Memantine-Containing Solid
`Pharmaceutical Dosage Forms Having an Extended Two-Stage
`Release Profile and Production Thereof,” issued on January 17, 1995
`Ex. 1010 K. Ditzler, Efficacy and Tolerability of Memantine in Patients with Dementia
`Syndrome, 41 DRUG RESEARCH 773 (1991)
`PCT International Publication No. WO 2004/012741, titled
`“Sustained Release Formulations Comprising Lamotrigine,”
`published on February 12, 2004
`Steven M. Troy et al., Bioavailability of Once-Daily Venlafaxine Extended
`Release Compared with the Immediate-Release Formulation in Healthy Adult
`Volunteers, 58 CURR.THER. RES. CLIN. E.492 (1997)
`Clinical Pharmacology and Biopharmaceutics Review, in Center for Drug
`Evaluation and Research Approval Package for: Application
`Number 21-487 (Oct. 2, 2003) (publicly available at
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-
`487_namenda_bioeqr_p1.pdf.)
`
`Ex. 1004
`
`Ex. 1005
`Ex. 1006
`Ex. 1007
`
`Ex. 1008
`Ex. 1009
`
`Ex. 1011
`
`Ex. 1012
`
`Ex. 1013
`
`v
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`

`
`
`
`Ex. 1020
`
`Ex. 1014 Namenda™ Approval Labeling Text, NDA 21-487
`Christoph Maier et al., Efficacy of the NMDA-receptor antagonist
`Ex. 1015
`memantine in patients with chronic phantom limb pain – results of a
`randomized double-blinded, placebo-controlled trial, 103 PAIN 277 (2003)
`Ex. 1016 Hans J. Möbius et al., Memantine Hydrochloride: Pharmacological and
`clinical profile, 40 DRUG TODAY 685 (2004)
`Ex. 1017 Gilbert S. Banker, Pharmaceutical Applications of Controlled Release: An
`Overview of the Past, Present, and Future, in MEDICAL APPLICATIONS OF
`CONTROLLED RELEASE: VOLUME II APPLICATIONS AND
`EVALUATION (Robert S. Langer, Ph.D. and Donald L. Wise, eds.,
`1984)
`Ex. 1018 Henry Brodaty, Efficacy of Once-Daily Galantamine Extended-Release in
`Patients with Mild to Moderate Alzheimer’s Disease, 62 NEUROLOGY
`A317 (Suppl 5) (2004)
`Ex. 1019 Qing Yang et al., Controlled Release Tacrine Delivery System for the
`Treatment of Alzheimer’s Disease, 8 DRUG DELIV. 93 (2001)
`Excerpt from the Prosecution History of U.S. Application No.
`11/399,879, November 5, 2010 Declaration of Dr. Gregory T. Went
`Excerpt from the Prosecution History of U.S. Application No.
`11/285,905, June 15, 2009 Declaration of Dr. Gayatri Sathyan
`Excerpt from the Prosecution History of U.S. Application No.
`11/399,879, February 8, 2011 Office Action
`Excerpt from the Prosecution History of U.S. Application No.
`11/399,879, April 4, 2011 Declaration of Dr. Sid Gilman
`U.S. Patent No. 6,194,000, titled “Analgesic Immediate and
`Controlled Release Pharmaceutical Composition,” issued February
`27, 2001
`Ex. 1025 Marina Pantev et al., Clinical and behavioural evaluation in long-term care
`patients with mild to moderate dementia under Memantine treatment, 6 Z
`GERONTOPSYCHOL PSCYHIATR 103 (1993)
`Yihong Qiu and Guohua Zhang, Research and Development Aspects of
`Oral Controlled-Release Dosage Forms, in HANDBOOK OF
`PHARMACEUTICAL CONTROLLED RELEASE TECHNOLOGY (Donald
`L. Wise, ed., 2000)
`
`Ex. 1024
`
`Ex. 1021
`
`Ex. 1022
`
`Ex. 1023
`
`Ex. 1026
`
`vi
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`

`
`
`
`Ex. 1027
`
`Ex. 1028
`
`Excerpt from the Prosecution History of U.S. Patent No. 8,362,085,
`September 6, 2012 Preliminary Amendment
`Excerpt from the Prosecution History of U.S. Application No.
`11/399,879, May 11, 2011 Amendment and Response to Office
`Action
`Excerpt from the Prosecution History of U.S. Application No.
`11/399,879, September 21, 2011 Notice of Allowance
`Ex. 1030 Douwe D. Breimer, An Integrated Pharmacokinetic and Pharmacodynamic
`Approach to Controlled Drug Delivery, 3 J. OF DRUG TARGET. 411 (1996)
`Bernard Rambeck and Peter Wolf, Lamotrigine Clinical
`Pharmacokinetics, 25 CLIN. PHARMACOKINET. 433 (1993)
`Ex. 1032 Monique Wakelkamp, et al, The influence of drug input rate on the
`development of tolerance to frusemide, 46 J. CLIN. PHARMACOL. 479 (1998)
`
`Ex. 1029
`
`Ex. 1031
`
`vii
`
`

`
`
`
`Pursuant to 35 U.S.C. §§ 311–319 and 37 C.F.R. § 42, Ranbaxy Laboratories
`
`Limited and Ranbaxy Inc. (collectively, “Ranbaxy” or “Petitioners”) petition for Inter
`
`Partes Review (“IPR”) of claims 1 through 12 of U.S. Patent 8,362,085 to Went et
`
`al., titled “Method for Administering an NMDA Receptor Antagonist to a Subject”
`
`(“the ’085 patent,” Ex. 1001). Concurrently filed herewith is a Power of Attorney
`
`pursuant to 37 C.F.R. § 42.10(b). Pursuant to 37 C.F.R. § 42.103, Petitioners authorize
`
`the PTO to charge Deposit Account 11-0060 for the fee set forth in 37 C.F.R. §
`
`42.15(a) and authorizes any additional fees to be charged to the same account.
`
`I. MANDATORY NOTICES
`A. Real Party-In-Interest (37 C.F.R. § 42.8(b)(1))
`Ranbaxy Laboratories Limited and Ranbaxy Inc. are the real parties-in-interest
`
`for Petitioners.
`
`Ranbaxy Inc. is a wholly owned subsidiary of Ranbaxy Holdings (U.K.) Ltd.,
`
`which is a wholly owned subsidiary of Ranbaxy (Netherlands) B.V., which is a wholly
`
`owned subsidiary of Ranbaxy Laboratories Ltd. Ranbaxy Laboratories Ltd. is a
`
`publicly held entity. Its shares are listed on the Stock Exchanges in India, viz.
`
`National Stock Exchange and The Stock Exchange, Mumbai. Its Global Depository
`
`Shares are listed on the Luxembourg Stock Exchange. Daiichi Sankyo Company,
`
`Ltd., a publicly traded entity on the Stock Exchanges in Japan, owns approximately
`
`64% of the outstanding shares of Ranbaxy Laboratories Ltd.’s stock.
`
`1
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`

`
`
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`Petitioners are not aware of any reexamination certificates or pending
`
`prosecution concerning the ’085 patent. Petitioners are parties to a pending litigation
`
`regarding infringement and invalidity of the ’085 patent, namely Forest Laboratories,
`
`Inc. et al v. Ranbaxy Inc. et. al, Civ. Action No. 14-cv-686, currently pending in the
`
`District of Delaware. There are also pending litigations regarding infringement and
`
`invalidity of the ’085 patent currently pending against additional parties in the District
`
`of Delaware, including Civ. Action Nos. 14-cv-121 , 14-cv-200, 14-cv-508, 14-cv-
`
`1058, and 14-cv-1271.
`
`There are also two pending applications claiming benefit to the ’085 patent,
`
`namely No. 14/081,643, filed on November 15, 2013, and No. 14/339,599, filed on
`
`July 24, 2014.
`
`C.
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel
`Anne Elise Herold Li
` (Reg. No. 53,181)
`KENYON & KENYON LLP
`One Broadway
`New York, NY 10004-1007
`ali@kenyon.com
`Tel: 212.908.6083
`Fax: 212.425.5288
`
`
`Back-up Counsel
`John W. Bateman
` (Reg. No. 41,602)
`KENYON & KENYON LLP
`1500 K Street, NW
`Washington, DC 20005
`jbateman@kenyon.com
`Tel: 202.220.4216
`Fax: 202.220.4201
`
`D.
`Service Information (37 C.F.R. § 42.8(b)(4))
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`contact information above. Petitioners consent to service by electronic mail at
`2
`
`

`
`
`
`jbateman@kenyon.com and ali@kenyon.com.
`
`II. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT
`As required by 37 C.F.R. § 42.104(a), Petitioners certify that the ’085 patent is
`
`available for IPR and that the Petitioners are not barred or estopped from
`
`requesting IPR on the grounds identified herein.
`
`III.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED
`Petitioners request inter partes review and cancellation of claims 1 through 12 of
`
`the ’085 patent on one or more of the grounds under 35 U.S.C. §§ 102 and 103 set
`
`forth herein. The ’085 patent is to be reviewed under pre-AIA §§ 102 and 103.
`
`Petitioners’ detailed statement of the reasons for the relief requested is set forth
`
`below in the section titled “Statement of Reasons for Relief Requested.” In
`
`accordance with 37 C.F.R. § 42.6(c), copies of the exhibits are filed herewith. In
`
`addition, this Petition is accompanied by the Declaration of Arthur H. Kibbe, Ph.D.
`
`(“Kibbe Decl.,” Ex. 1002).
`
`IV. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`A petition for inter partes review must demonstrate “a reasonable likelihood
`
`that the petitioner would prevail with respect to at least 1 of the claims challenged in
`
`the petition.” 35 U.S.C. § 314(a). This Petition meets this threshold. For each of the
`
`grounds of unpatentability proposed, there is a reasonable likelihood that Petitioners
`
`will prevail with respect to at least one of the challenged claims.
`
`3
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`

`
`
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`V.
`
`
`
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`A. Grounds of Unpatentability
`
`As set forth in detail below, claims 1–12 of the ’085 patent are unpatentable
`
`based on the following grounds:
`
`Ground 1: Claims 1 and 7 Are Anticipated by Rastogi
`
`Ground 2: Claims 1–12 Are Obvious Over Nürnberg in View of Ditzler, the
`
`’741 PCT and the Namenda 2003 Label
`
`Ground 3: Claims 1–12 Are Obvious Over the ’741 PCT in View of Ditzler
`
`and the Namenda 2003 Label
`
`Ground 4: Claims 1–12 Are Obvious Over Rastogi in View of Ditzler and the
`
`’741 PCT
`
`B. Overview of the ’085 Patent
`The challenged claims of the ’085 patent are generally directed to a method for
`
`treating a patient with a neurological disorder such as Alzheimer’s disease or
`
`dementia that comprises administering once daily a sustained release1 oral dosage
`
`
`
`1
`
`The claims of the ’085 patent refer to a “sustained release oral dosage form,”
`
`but the specification of the ’085 patent uses the terms “sustained release,” “extended
`
`release,” “modified release,” and “controlled release” interchangeably. Ex. 1001 at
`
`col. 2, ll. 39–43 and col. 3, ll. 23–25.
`
`4
`
`

`
`
`
`form containing a certain amount of memantine (either 22.5 to 30 mg, 25 to 30 mg,
`
`or 28 mg) that produces certain pharmacokinetic (PK) parameters when
`
`administered. Ex. 1001 at Abstract; see also Kibbe Decl., Ex. 1002 at ¶ 33. The
`
`claimed PK parameters each relate to the “change in mean plasma concentration of
`
`memantine as a function of time” (“dC/dT”). In different ways, these PK
`
`parameters require that the initial rate of rise of the concentration of memantine in
`
`the plasma produced by the claimed sustained release oral dosage form be slower
`
`than that produced by an “immediate release” (or “IR”) formulation. For example,
`
`some claims require that the dC/dT of the claimed sustained release oral dosage
`
`form be 50% or less than the dC/dT from Time 0 to Tmax of an IR formulation
`
`containing the same amount of memantine. The specification of the ’085 patent
`
`indicates that the claimed sustained release oral dosage forms will reduce side effects
`
`and increase patient compliance. Ex. 1001 at col. 7, l. 56–col. 8, l. 5; see also Kibbe
`
`Decl., Ex. 1002 at ¶ 35.
`
`C.
`Prosecution Background
`The application that issued as the ’085 patent claims priority to a chain of non-
`
`provisional and provisional applications. The application that issued as the ’085
`
`patent was filed June 28, 2012. On the following day, a declaration by one of the
`
`inventors, Dr. Gregory T. Went (“the Went declaration,” Ex. 1003), was submitted.
`
`In his declaration, Dr. Went argued that one of ordinary skill would not have
`
`been motivated to make a sustained release oral dosage form containing 22.5 to 30 mg
`
`5
`
`

`
`
`
`of memantine for several reasons (discussed in detail in section VI1(b) below). Ex.
`
`1003 at ¶¶ 4–7. Dr. Went also described the results of several experiments comparing
`
`the side effects produced by an IR memantine formulation with various sustained
`
`release memantine formulations (referred to as “extended release” or “ER”
`
`formulations in the declaration). Id. at ¶¶ 8–16. Dr. Went argued that these
`
`experiments showed that sustained release memantine formulations with an initial rate
`
`of rise (dC/dT) in memantine plasma concentration that was less than 50% of the
`
`dC/dT for an IR formulation over the same time period produced fewer side effects
`
`than those that did not meet the “less than 50%” limitation., and that this was an
`
`unexpected result that supported patentability. Id. at ¶ 13; see also Kibbe Decl., Ex.
`
`1002 at ¶ 37–39.
`
`The examiner issued a Notice of Allowance to Applicants on September 24,
`
`2012. While Applicants had argued in support of the claims that there was both a
`
`lack of motivation to develop the claimed subject matter and that there had been
`
`unexpected the results, the examiner only relied on the unexpected results component
`
`in the allowance. Ex. 1004 at 2; see also Kibbe Decl., Ex. 1002 at ¶ 40.
`
`D. Priority Date of the ’085 Patent
`The earliest priority date to which the ’085 patent is even possibly entitled is
`
`April 6, 2005, the filing date of provisional application No. 60/669,290. The ’085
`
`patent claims priority to two earlier provisional applications, provisional application
`
`No. 60/630,885 filed November 23, 2004 (“the ’885 provisional,” Ex. 1005) and
`
`6
`
`

`
`
`
`provisional application No. 60/635,365, filed December 10, 2004 (“the ’365
`
`provisional,” Ex. 1006). However, the claims of the ’085 patent are not entitled to
`
`the filing date of the ’885 and ’365 provisionals because they do not provide written
`
`description support for several limitations in those claims.
`
`Specifically, the ’885 and ’365 provisionals do not provide written description
`
`support for at least the limitations requiring (1) a sustained release oral dosage form
`
`that provides a dC/dT that is “less than about 50% of the dC/dT provided by the
`
`same quantity of an immediate release form of memantine, determined in a time
`
`period between 0-Tmax of the immediate release form of memantine” (Ex. 1001,
`
`claims 1–6), (2) a sustained release oral dosage form that provides a dC/dT that is
`
`“less than about 50% of the dC/dT provided by the same quantity of an immediate
`
`release form of memantine, determined in a time period between 0 hours and 6 hours
`
`of administration of memantine” (id. at claims 7–12), (3) a sustained release oral
`
`dosage form that provides a dC/dT that is “2.1 ng/mL/hr or less, determined in a
`
`time period of 0 to 4 hours” (id. at claims 1–12), or (4) a sustained release oral dosage
`
`form that provides a dC/dT that is 2.1 ng/mL/hr or less “determined in a time
`
`period of 2 to 4 hours” (id. at claims 2, 4, 6, 8, 10 and 12). See Kibbe Decl., Ex. 1002
`
`at ¶ 43.
`
`The ’885 provisional is generally directed to “methods and compositions for
`
`administering an NMDA receptor antagonist (e.g., memantine) to a subject,” and
`
`describes sustained release oral dosage forms containing memantine . Ex. 1005 at
`7
`
`

`
`
`
`Abstract; see also p. 3, ll. 13–23; p. 4, ll. 25–29; p. 6, l. 10–p. 10, l. 27. While briefly
`
`mentioning a release profile of the NMDA receptor antagonist, the ’885 provisional
`
`application provides no specific pharmacokinetics of a sustained release oral dosage
`
`form. Id. at p. 5, ll. 11–17. Moreover, the dC/dT parameters recited in the claims of
`
`the ’085 patent are not mentioned and cannot be calculated from the disclosure of the
`
`’885 provisional. See Kibbe Decl., Ex. 1002 at ¶ 44.
`
`The ’365 provisional is directed to methods for treating tuberous sclerosis
`
`complex with an adamantine derivative, including memantine. Ex. 1006 at 3–4, 8–9.
`
`The only disclosure of sustained release oral dosage forms is the statement that “[t]he
`
`formulations can be administered in either a local or systemic manner or in a depot or
`
`sustained release fashion.” Ex 1006 at 12. The ’365 provisional makes no other
`
`mention of sustained release formulations and does not provide any pharmacokinetic
`
`parameters for such formulations. See Kibbe Decl., Ex. 1002 at ¶ 45.
`
`For a later application to be entitled to the priority date of an earlier
`
`application, the earlier application must provide written description support for the
`
`claims of the later application. See 35 U.S.C. §§ 119, 120 (pre-AIA); Lockwood v. Am.
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`Airlines, Inc., 107 F.3d 1565, 1571 (Fed. Cir. 1997). Here, the ’885 and ’365
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`provisionals do not provide written description support for the claim limitations
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`recited above. Accordingly, the claims of the ’085 patent are not entitled to claim
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`priority to either of these provisionals, and the earliest effective filing date to which
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`the ’085 entitled is April 6, 2005. During prosecution of the applications leading to
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`the ’085 patent, there was no substantive consideration of whether the claims were
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`entitled to the filing dates of the ’885 or ’365 provisionals.
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`E. Level of Ordinary Skill in the Art
`A person of ordinary skill in the art at the time of the alleged invention of the
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`’085 patent would have had at least a Master’s degree or Ph.D. degree in the field of
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`pharmaceutical sciences or a related discipline and several years of experience
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`formulating pharmaceutically active compounds in various dosage forms, including
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`immediate release and sustained release dosage forms. A person of ordinary skill
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`could have a lower level of formal education if such a person had a higher degree of
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`experience. A person of ordinary skill in the art would collaborate with others having
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`expertise in methods of treating Alzheimer’s disease and dementia. A person of
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`ordinary skill in the art would understand the references referred to herein and have
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`the capability to draw inferences from them. See Kibbe Decl., Ex. 1002 at ¶ 14.
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`F. Claim Construction
`The claims of the ’085 patent are presumed to take on their ordinary and
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`customary meaning based on the broadest reasonable interpretation of the claim
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`language. Petitioners do not believe that Applicants attributed any special meanings
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`to the claim terms in the ’085 patent when the broadest reasonable interpretation
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`standard is applied. Petitioners’ positions regarding the scope of the claims should
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`not be construed as an assertion regarding the appropriate claim scope in other
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`adjudicative forums, where a different claim interpretation standard may apply.
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`G. Patents and Printed Publications Relied On
`Petitioners rely on the following patents and publications:
`1.
`Rastogi – U.S. Patent No. 8,039,009 (Ex. 1007)
`U.S. Patent No. 8,039,009, titled “Modified Release Formulations of
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`Memantine Oral Dosage Forms” (“Rastogi,” Ex. 1007) was filed on June 16, 2005,
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`and claims priority to Provisional Application No. 60/581,242 (“the ’242 Provisional
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`application,” Ex. 1008) filed on June 17, 2004, which is prior to the earliest filing date
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`for the ’085 patent. Accordingly, the subject matter commonly disclosed in both
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`Rastogi and the provisional application is prior art to the ’085 patent under 35 U.S.C.
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`§ 102(e) (pre-AIA). See In re Giacomini, 612 F.3d 1380, 1383–85 (Fed Cir. 2010).
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`Rastogi was not of record during the prosecution of the applications leading to the
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`’085 patent. Although a published version of the U.S. non-provisional application
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`(US 2006/0051416 A1) that led to Rastogi, as well as a published PCT corresponding
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`to Rastogi (WO 2006/009769 A1), were cited by Applicants during the prosecution of
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`the applications leading to the ’085 patent, there was no substantive discussion of
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`either reference during prosecution.
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`Rastogi discloses once-daily, sustained release formulations containing
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`memantine for the treatment of Alzheimer’s disease. Ex. 1007 at col. 2, l. 65–col. 3, l.
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`7; col. 3, ll. 17–31; col. 5, l. 66–col. 6, l. 6; col. 9, ll. 44–51; col. 10, l. 18–21; Ex. 1008
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`at p. 5, ll. 26–31; p. 6, ll. 8–12; p. 9, ll. 17–21; p. 14, ll. 5–9; p. 14, l. 30–p. 15, l.1; see
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`also Kibbe Decl., Ex. 1002 at ¶ 49.
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`Rastogi indicates there is motivation for making a once-daily, sustained release
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`formulation for the treatment of Alzheimer’s because such a formulation will increase
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`patient compliance and decrease adverse events (i.e., side effects), stating:
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`Currently, a dosing regimen of memantine of twice a day is
`employed using immediate release tablets. This may be
`undesirable because patient compliance decreases as the
`frequency of taking a drug increases. Moreover, administration of
`an immediate-release tablet can lead to greater frequency of
`adverse events due to a faster rate of absorption. . . .There is
`therefore an existing and continual need for a once a day modified
`release formulation containing memantine. . . .
`Ex. 1007 at col. 2, l. 65–col. 3, l. 7; Ex. 1008 at p. 5, ll. 26–31; see also Kibbe Decl., Ex.
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`1002 at ¶ 50.
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`
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`Rastogi discloses memantine hydrochloride forms containing about 10 mg to
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`about 80 mg per tablet. Ex. 1007 at col. 3, ll. 32–55; Ex. 1008 at p. 6, ll. 16–26; see also
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`Kibbe Decl., Ex. 1002 at ¶ 52.
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`
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`Further, Rastogi describes “6-hour release” and “12-hour release”
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`formulations, also referred to as “6 hour dissolution” and “12 hour dissolution”
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`formulations. For the 12-hour release formulations, about 70 to 80% of the active
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`ingredient (memantine hydrochloride) is released after about 12 hours following entry
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`into the use environment. Ex. 1007 at col 3, ll. 32–35; Ex. 1008 at p. 6, ll. 10–15; see
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`also Kibbe Decl., Ex. 1002 at ¶ 51. Example 1 describes 12-hour release formulations
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`made using a polymeric matrix, each of which includes at least one component that
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`sustains release of memantine. Ex. 1007 at Table 1; col. 12, ll. 37–43; Ex. 1008 at p.
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`16, Table 1; p. 16, ll. 10–14.
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`Rastogi also discloses a crossover pharmacokinetic study in which subjects
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`were given each of three treatments one time. The treatments were: Treatment A (or
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`“IR Formulation”), consisting of two tablets of 10 mg of an IR formulation, one
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`given at 8 a.m. and one given at noon; Treatment B (or “MR Formulation I”),
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`consisting of 20 mg of a modified release formulation with a six hour dissolution
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`administered at 8 a.m.; and Treatment C (or “MR Formulation II”), consisting of a
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`second modified release formulation with 20 mg and a twelve hour dissolution
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`administered at 8 a.m. Ex. 1007 at col. 15, ll. 33–45; Ex. 1008 at p. 18, l. 25–p. 19, l. 3.
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`Each subject received a different one of the three treatment regimens on study days 1,
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`22, and 43, allowing a 21-day washout period in between each treatment. Ex. 1007 at
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`col. 15, ll. 33–45; Ex. 1008 at p. 18, l. 25–p. 19, l. 3; see also Kibbe Decl., Ex. 1002 at ¶
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`53. In this way, each subject received each of the three treatment regimens one time
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`(one on day 1, a different one on day 22, and a third one on day 43). Figure 7 of
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`Rastogi presents mean plasma concentrations of memantine during the first 24 hours
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`post-dosage for each treatment. Ex. 1007 at col. 17, l. 41–42; Ex. 1008 at p. 21, l. 19–
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`20; see also Kibbe Decl., Ex. 1002 at ¶ 54. Thus, for example, the curve for the second
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`modified release formulation (Treatment C) represents the mean plasma
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`concentration levels for the subjects who received Treatment C on day 1, the subjects
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`who received Treatment C on day 22, and the subjects who received Treatment C on
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`day 43.
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`2. Nürnberg – U.S. Patent No. 5,382,601 (Ex. 1009)
`U.S. Patent 5,382,601, titled “Memantine-Containing Solid Pharmaceutical
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`Dosage Forms Having an Extended Two-Stage Release Profile and Production
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`Thereof,” (“Nürnberg,” Ex. 1009) issued on January 17, 1995, which is more than one
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`year prior to the earliest filing date for the ’085 patent. Accordingly, Nürnberg is prior
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`art under 35 U.S.C. § 102(b) (pre-AIA).
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`Nürnberg discloses sustained release oral dosage forms containing “agents
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`influencing the demential syndrome such as memantine.” Ex. 1009 at col. 5, ll. 49–50;
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`see also col. 1, ll. 9–23; Kibbe Decl., Ex. 1002 at ¶ 56. Nürnberg discloses that among
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`available pharmaceutical active ingredients, the “[m]ost preferred is memantine.” Ex.
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`1009 at col. 5, l. 63. Example 1 describes an extended-release tablet containing 20 mg
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`of memantine. Id. at col. 7, ll. 17–35; see also Kibbe Decl., Ex. 1002 at ¶ 58.
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`Nürnberg describes a matrix-controlled release system that includes a water-
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`soluble salt of casein and a