IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner
`
`v .
`
`SHIRE LABORATORIES, INC.,
`Patent Owner.
`
`U.S. Patent No. RE41,148 to Burnside et al.
`Issue Date: Feb. 23, 2010
`Title: Oral Pulsed Dose Drug Delivery System
`
`Inter Partes Review No.: IPR2016-XXXX
`
`Petition for Inter Partes Review of U.S. Patent No. RE41,148 Under
`35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`TABLE OF CONTENTS
`
`Page
`
`I.
`II.
`III.
`
`C.
`
`INTRODUCTION ...........................................................................................1
`OVERVIEW....................................................................................................1
`STANDING (37 C.F.R. § 42.104(a); PROCEDURAL
`STATEMENTS)..............................................................................................4
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))......................................4
`A.
`Each Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) ...........................4
`B.
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2))..............................4
`1.
`Judicial Matters...........................................................................4
`2.
`Administrative Matters ...............................................................5
`Designation of Lead and Back-Up Counsel and Service (37
`C.F.R. §§ 42.8(b)(3), 42.8(b)(4), 42.10(a), and 42.10(b)):...................5
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFORE (37 C.F.R. § 42.22(a))..........................................6
`THE ’148 PATENT.........................................................................................6
`A.
`CLAIM CONSTRUCTION ..................................................................7
`VII. PERSON OF SKILL IN THE ART (“POSA”) & STATE OF THE
`ART .................................................................................................................9
`VIII. IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b))...................9
`A.
`The Scope and Content of the Prior Art..............................................10
`1.
`The ’284 Patent .........................................................................10
`2.
`PDR 1997..................................................................................12
`3.
`Brown........................................................................................13
`4.
`The ’131 Patent .........................................................................14
`
`V.
`
`VI.
`
`i
`
`

`

`Slattum ......................................................................................15
`5.
`Invalidity Analysis.........................................................................................16
`A.
`Claims 1-20 Would Have Been Obvious Over the ’284 Patent
`in Light of the PDR 1997, Brown, the ’131 Patent, and Slattum .......16
`1.
`Differences Between the Claims and the Prior Art ..................16
`a.
`Independent Claim 1 and Its Dependent Claims 2-
`11 and 15-20 ...................................................................16
`(i)
`Claim 1 .................................................................16
`(ii)
`Claim 2 .................................................................30
`(iii) Claims 3 and 4......................................................34
`(iv) Claim 5 .................................................................36
`(v)
`Claim 6 .................................................................37
`(vi) Claim 7 .................................................................40
`(vii) Claim 8 .................................................................41
`(viii) Claim 9 .................................................................42
`(ix) Claim 10 ...............................................................42
`(x)
`Claim 11 ...............................................................47
`(xi) Claims 15 and 16..................................................47
`(xii) Claim 17 ...............................................................47
`(xiii) Claim 18 ...............................................................50
`(xiv) Claim 19 ...............................................................51
`(xv) Claim 20 ...............................................................52
`Independent Claim 12 and Its Dependent Claims
`13 and 14.........................................................................53
`(i)
`Claim 12 ...............................................................53
`(ii)
`Claim 13 ...............................................................60
`(iii) Claim 14 ...............................................................61
`Objective Indicia of Non-Obviousness ...............................................61
`1.
`No Unexpected Results Over the Closest Prior Art..................62
`2.
`Other Objective Indicia.............................................................62
`CONCLUSION..............................................................................................63
`
`B.
`
`b.
`
`IX.
`
`X.
`
`ii
`
`

`

`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc.,
`IPR2013-00368...................................................................................................60
`Biomarin Pharmaceticals Inc. v. Genzyme Therapeutics Products
`Ltd.,
`IPR2013-00534...................................................................................................26
`Cuozzo Speed Techs., LLC v. Lee,
`579 U.S. ___, No. 15-446, 2016 WL 3369425 (2016).........................................8
`In re Aller,
`220 F.2d at 456-57.......................................................................................passim
`In re Fout,
`675 F.2d 297 (C.C.P.A. 1982)................................................................19, 25, 47
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ...................................................................passim
`In re Peterson,
`315 F.3d 1329 ..............................................................................................passim
`In re Woodruff,
`919 F.2d 1575 (Fed. Cir. 1990) ...................................................................passim
`Merck & Co. v. Biocraft Labs., Inc.,
`874 F.2d 804 (Fed. Cir. 1989) ............................................................................12
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................59
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2008) ..........................................................................60
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 Fed App’x 978 (Fed. Cir. 2010) ..................................................................60
`
`iii
`
`

`

`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) ......................................................................2, 25
`Shire LLC et al v. Abhai LLC,
`No. 1:15-cv-13909-WGY (D. Mass.)...................................................................4
`Shire LLC v. Amerigen Pharmaceuticals Ltd.,
`No. 1:14-cv-06095-RMB-JS (D.N.J.)...................................................................4
`Shire LLC v. CorePharma, LLCC,
`No. 1-14-cv-05694 (D.N.J.)..................................................................................4
`Shire LLC v. Neos Therapeutics, Inc.,
`3-13-cv-01452 (N.D. Tex.)...................................................................................4
`Shire LLC v. Par Pharmaceutical, Inc. et al,
`No. 1-15-cv-01454 (D.N.J.)..................................................................................4
`Shire LLC v. Watson Pharms., Inc., et al,
`No. 1-11-cv-02340 (S.D.N.Y.) .............................................................................4
`Vandenberg v. Dairy Equip. Co.,
`740 F.2d 1560 (Fed. Cir. 1984) ..........................................................................61
`STATUTES
`35 U.S.C. § 102(b) ............................................................................................passim
`OTHER AUTHORITIES
`37 C.F.R. § 42(a)(1)...................................................................................................4
`37 C.F.R. § 42.6(d) ....................................................................................................9
`37 C.F.R. § 42.8(b)(1)................................................................................................4
`37 C.F.R. § 42.8(b)(2)................................................................................................4
`37 C.F.R. § 42.8(b)(3)................................................................................................5
`37 C.F.R. § 42.10(b) ..................................................................................................3
`37 C.F.R. §42.63(e)....................................................................................................3
`
`iv
`
`

`

`37 C.F.R. § 42.100(b) ................................................................................................8
`
`
`37 C.F.R. § 42.100(b) .............................................................................................. ..837 C.F.R. § 42.100(b) ................................................................................................ 837 C.F.R. § 42.100(b) ................................................................................................ 8
`37 C.F.R. § 42.104(a).................................................................................................3
`
`
`37 C.F.R. § 42.104(a) ............................................................................................... ..337 C.F.R. § 42.104(a) ................................................................................................. 337 C.F.R. § 42.104(a) ................................................................................................. 3
`37 C.F.R. § 42.104(b) ................................................................................................9
`
`
`37 C.F.R. § 42.104(b) .............................................................................................. ..937 C.F.R. § 42.10403) ................................................................................................ 937 C.F.R. § 42.10403) ................................................................................................ 9
`37 C.F.R. § 42.106(a).................................................................................................3
`
`
`37 C.F.R. § 42.106(a) ............................................................................................... ..337 C.F.R. § 42.106(a) ................................................................................................. 337 C.F.R. § 42.106(a) ................................................................................................. 3
`
`v
`
`

`

`Petitioner’s Exhibit List
`
`Description
`Burnside et al., U.S. Patent No. RE41,148, “Oral Pulsed Dose Drug
`Delivery System”
`Declaration of David Auslander, Ph.D.
`Curricula Vitae of David Auslander, Ph.D.
`Amidon et al., U.S. Patent No. 5,229,131, “Pulsatile Drug Delivery
`System”
`Mehta et al., U.S. Patent No. 5,837,284, “Delivery of Multiple Doses
`of Medication”
`Physician’s Desk Reference 28th edition (1974)
`Physician’s Desk Reference 47th edition (1993)
`Physician’s Desk Reference 49th edition (1995)
`Physician’s Desk Reference 51st edition (1997)
`ANSEL, POPOVICH & ALLEN, PHARMACEUTICAL DOSAGE
`FORMS AND DRUG DELIVERY SYSTEMS 220, 223 (6th ed.
`1995)
`Gerald L. Brown et al., Behavior and Motor Activity Response in
`Hyperactive Children and Plasma Amphetamine Levels Following a
`Sustained Release Preparation, J. Am. Academy of Child Psychiatry,
`vol. 19, 255 (1980)
`Charles S. L. Chiao, Ph.D. & Joseph R. Robinson, PhD., Sustained-
`Release Drug Delivery Systems, 1660-1675, in REMINGTON:
`THE SCIENCE AND PRACTICE OF PHARMACY (19th ed.
`1995)
`W. H. Hartung & J. C. Munch, Amino Alcohols, VI. The
`Preparation and Pharmacodynamic Activity of Four Isomeric
`Phenylpropylamines, 53 J. AM. CHEM. SOC. 1875, 1875-79
`(1931)
`Brian B. Hoffman & Robert J. Lefkowitz, Catecholamines,
`Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, in
`GOODMAN & GILMAN’S THE PHARMACOLOGICAL BASIS
`OF THERAPEUTICS, 199 (9th ed. 1996)
`The Merck Index (Susan Budavari, et al., eds., 11th ed. 1989)
`
`Exhibit #
`1001
`
`1002
`1003
`1004
`
`1005
`
`1006
`1007
`1008
`1009
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`vi
`
`

`

`Exhibit #
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`1026
`
`1027
`1028
`1029
`1030
`1031
`
`1032
`
`1033
`
`Description
`Stuart C. Porter, Ph.D., Coating of Pharmaceutical Dosage Forms,
`1650-1659, 1653 in REMINGTON: THE SCIENCE AND
`PRACTICE OF PHARMACY (19th ed. 1995)
`Patricia K. Sonsalia, Central Nervous System Stimulants, in
`REMINGTON: THE SCIENCE AND PRACTICE OF
`PHARMACY 1233-34 (19th ed. 1995)
`Edward Stempel, Prolonged-Action Medication, in DISPENSING
`OF MEDICATION, 1024 (Eric W. Martin ed., 7th ed. 1971)
`1995 United States Pharmacopeia and National Formulary, USP 23-
`NF 18 (1994)
`Patent Owner Preliminary Response, dated January 19, 2016
`Petition for Inter Partes Review of USPN RE42,096, dated October
`1, 2015
`Decision Instituting Inter Partes Review of USPN RE42,096,
`IPR2015-02009
`Dahlinder et al., U.S. Patent No. 4,927,640, “Controlled Release
`Beads Having Glass or Silicon Dioxide Core”
`Arwidsson et al., U.S. Patent No. 5,783,215, “Pharmaceutical
`Preparation”
`Select Portions of NDA 11522
`“Adderall and Other Drugs for Attention-Deficit/Hyperactivity
`Disorder” in The Medical Letter (1994)
`Physician’s Desk Reference 48th edition (1994)
`Records from the U.S. Copyright Office for PDR 1997
`Declaration of Anthony Palmieri, Ph.D.
`Curriculum Vitae of Anthony Palmieri
`Patricia W. Slattum, et al., Comparison of Methods for the
`Assessment of Central Nervous System Stimulant Response after
`Dextroamphetamine Administration to Healthy Male Volunteers, J.
`Clin. Pharmacol., vol. 36 no. 11 (1996)
`Leslie Z. Benet, et al., Basic Principles of Pharmacokinetics,
`Toxicologic Pathology, vol. 23 no. 2 (1995)
`6/24/2002 Office Action by Examiner, US Application No.
`09/807,462
`
`vii
`
`

`

`Exhibit #
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`Description
`10/24/2002 Applicant Arguments/Remarks Made in Amendment,
`US Application No. 09/807,462
`4/21/2003 Applicant Arguments/Remarks After Final Rejection, US
`Application No. 09/807,462
`6/10/2003 Applicant Arguments/Remarks Made in Amendment, US
`Application No. 09/807,462
`Burt Angrist, et al., Early Pharmacokinetics and Clinical Effects of
`Oral D-Amphetamine in Normal Subjects, Biol. Psychiatry, vol. 22
`(1987)
`Orville N. Hinsvark, et al., The Oral Bioavailability and
`Pharmacokinetics of Soluble and Resin-Bound Forms of
`Amphetamine and Phentermine in Man, J. of Pharmacokinetics and
`Biopharmaceutics, vol. 1 No. 4 (1973)
`Boris Birmaher, et al., Sustained Release Methylphenidate:
`Pharmacokinetic Studies in ADDH Males, J. of the Am. Academy of
`Child & Adolescent Psychiatry, vol. 28, no. 5 (1989)
`Specifications and Test Methods for Eudragit® RL 12,5 and
`Eudragit® RL 100 Eudragit® RS 12,5 and Eudragit® RS 100,
`Röhm Pharma Polymers (July 1999)
`
`viii
`
`

`

`I.
`
`INTRODUCTION
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) petitions for Inter Partes Review,
`
`and seeks cancellation of claims 1-20 (“challenged claims”) of U.S. Patent No.
`
`RE41,148 (“the ’148 patent”) (EX1001), which according to the current records of
`
`the USPTO is assigned to Shire LLC (“Patent Owner”).
`
`II. OVERVIEW
`
`Generally speaking,
`
`the ’148 patent purports to cover a mixture of
`
`amphetamine base salts, such as the four amphetamine-salt combination of
`
`Adderall®, wherein the dosage form contains an both immediate-release and a
`
`delayed enteric release dose that is: (1) allegedly sufficient to maintain an effective
`
`level of amphetamine base salts in the patient over the course of at least 8 hours
`
`without further administration of amphetamine salts; and (2) will produce a plasma
`
`concentration versus time curve having an area under the curve (AUC) of about 467
`
`to about 714 ng hr/mL from a “total dose” of 20mg. See, e.g., EX1001 Claim 1. The
`
`dosage form is purported to be useful for treating Attention Deficit Hyperactivity
`
`Disorder (ADHD). See, Id. 8:4-11.
`
`The patentee will not dispute that prior to the earliest priority date for the ’148
`
`patent, the specific pharmaceutically active amphetamine salts, such as those used
`
`in Adderall® (an immediate-release product), were well-known in the art for treating
`
`ADHD. EX1009 at 2210. The ’148 patent does nothing more than modify then
`
`

`

`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
`
`existing amphetamine salt products to include a delayed-release component, and
`
`then claim the resulting pharmacokinetic parameters.
`
`In re Huai-Hung Kao, 639
`
`F.3d 1057, 1070 (Fed. Cir. 2011) (sustaining Board’s obviousness determination for
`
`a claim that recited pharmacokinetic parameters (i.e., Cmax) explaining that such
`
`parameters are “an inherent property . . . present both in controlled release and
`
`immediate release formulations of that drug.”); Santarus, Inc. v. Par Pharm., Inc.,
`
`694 F.3d 1344, 1354 (Fed. Cir. 2012) (an obvious formulation does not “become
`
`patentable merely by testing and claiming an inherent property.”); In Re Baxter
`
`Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“Mere recognition of latent
`
`properties in the prior art does not render nonobvious an otherwise known
`
`invention.”); In re Prindle, 297 F.2d 251, 254 (CCPA 1962).
`
`A person of ordinary skill in the art (“POSA”), however, would have been
`
`motivated to modify the immediate-release form of the amphetamine salt products
`
`(i.e., Adderall®) because it was known that the immediate-release formulations
`
`presented problems such as: (i) amphetamine abuse, (ii) the inconvenience of twice-
`
`a-day administration, (EX1001 at 3:23-30), and (iii) the stigmatism felt by school
`
`children when having to take the second dose in school as part of a twice-a-day
`
`formulation. EX1002, ¶¶36-37. A POSA would have sought to formulate a once-
`
`a-day capsule of the four-amphetamine salt combination of Adderall® to include a
`
`delayed release component to avoid such problems. Id., at ¶38.
`
`2
`
`

`

`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
`
`Modifying parameters to control delayed release profiles were known before
`
`the priority date of the ’148 patent. See, e.g., EX1005, Table 1. For example, by
`
`changing parameters such as the ratios of polymers, amount of coating, amount of
`
`talc, and curing time, U.S. Patent No. 5,837,284 (“the ’284 patent”) (EX1005)
`
`teaches a delayed release profile that resulted in substantially all of the drug
`
`methylphenidate being released after 10 hours. Methylphenidate is “a mild central
`
`nervous system stimulant with pharmacological activity qualitatively similar to that
`
`of amphetamines,” Id. at 2:5-16. EX1005, 13:57-60; 14:21-45. Moreover, the ’284
`
`patent teaches that the delayed release component can exceed the peak plasma
`
`concentration of the immediate release component and other pharmacokinetic
`
`parameters such as area under the curve (“AUC”) and Cmax. EX1005, 5:51-56. In
`
`fact, in reference to the above discussed ’284 patent, in an IPR (IPR2015-02009) for
`
`the parent patent (RE42096), the patent owner admitted that the ’284 patent teaches
`
`the required parameters of a delayed enteric release dosage that lasts for 3-10 hours.
`
`(EX1020, Patent Owner Preliminary Response, dated January 19, 2016 at 16:12-16).
`
`To the extent a POSA would have looked at any further guidance beyond the
`
`’284 patent, the POSA would have only had to look to U.S. Patent No. 5,229,131
`
`(“the ’131 patent”) (EX1004) and known pharmacokinetic data (EX1031, Slattum
`
`at 1044) to arrive at the alleged invention of the ’148 patent with a reasonable
`
`expectation of success.
`
`3
`
`

`

`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
`
`III.
`
`STANDING (37 C.F.R. § 42.104(a); PROCEDURAL STATEMENTS)
`
`Petitioner certifies that (1) the ’148 patent is available for IPR; and (2)
`
`Petitioner is not barred or estopped from requesting IPR of any claim of the ’148
`
`patent on the grounds identified herein. This Petition is filed in accordance with 37
`
`C.F.R. § 42.106(a). Filed herewith are a Power of Attorney and an Exhibit List
`
`pursuant to § 42.10(b) and § 42.63(e). The required fee is paid through an online
`
`credit card, and the Office is authorized to charge any fee deficiencies and credit
`
`overpayments to Deposit Acct. No. 160605 (Customer ID No. 00826).
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`
`Each Real Party-In-Interest (37 C.F.R. § 42.8(b)(1))
`A.
`Mylan Pharmaceuticals Inc., Mylan Inc. and Mylan N.V.
`
`B.
`
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2))
`
`Judicial Matters
`1.
`The ’148 patent is currently the subject, as the parent patent or current reissue
`
`form, of the following litigations: Shire LLC v. Amerigen Pharmaceuticals Ltd., No.
`
`1:14-cv-06095-RMB-JS (D.N.J.); Shire LLC et al v. Abhai LLC, No. 1:15-cv-13909-
`
`WGY (D. Mass.); Shire LLC v. Par Pharmaceutical, Inc. et al, No. 1-15-cv-01454
`
`(D.N.J.); Shire LLC v. CorePharma, LLCC, No. 1-14-cv-05694 (D.N.J.); Shire LLC
`
`v. Neos Therapeutics, Inc., 3-13-cv-01452 (N.D. Tex.); Shire LLC v. Watson
`
`Pharms., Inc., et al, No. 1-11-cv-02340 (S.D.N.Y.).
`
`4
`
`

`

`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
`
`Administrative Matters
`2.
`Petitioner is also aware of at least the following related family members:
`
`application No. 11/091,010 (“the ’010 application”), now the ’148 patent, is a reissue
`
`of application No. 09/807,462 (“the ’462 application”), now U.S. Patent No.
`
`6,605,300, which is a National Stage Entry of PCT/US99/24554, which is a
`
`continuation-in-part of 09/176,542 (“the ’542 application”), now U.S. Patent No.
`
`6,322,819 (“the ’819 patent”). Related family member application 11/091,011 (“the
`
`’011 application”) is now patented as U.S. Patent No. RE 42,096 (“the ’096 patent”).
`
`Related family member applications 10/172,705 and 10/758,417 are now
`
`abandoned. Petitioners have previously filed, a Petition for inter partes review of
`
`RE 42,096 (IPR2016-01033). In addition, the ’096 patent is currently the subject of
`
`Inter Partes Review (IPR2015-02009) filed by Petitioner Amerigen.
`
`C.
`
`Designation of Lead and Back-Up Counsel and Service (37 C.F.R.
`§§ 42.8(b)(3), 42.8(b)(4), 42.10(a), and 42.10(b)):
`
`Lead Counsel:
`
`Jitendra Malik, Ph.D.
`
`(Registration No.
`
`55,823;
`
`jitty.malik@alston.com). Backup Counsel: Bryan L. Skelton, Ph.D. (Registration
`
`No. 50,893; bryan.skelton@alston.com); James Abe (Registration No. 61,182;
`
`james.abe@alston.com);
`
`Brianna
`
`Kadjo
`
`(Registration
`
`No.
`
`74,307;
`
`brianna.kadjo@alston.com). Please direct all correspondence to lead counsel at the
`
`following address: 4721 Emperor Boulevard, Suite 400, Durham, North Carolina
`
`5
`
`

`

`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
`
`27703. Petitioner consents to email service. Telephone: (919) 862-2210. Facsimile:
`
`(919) 862-2260. Petitioner consents to email service.
`
`V.
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFORE (37 C.F.R. § 42.22(a))
`
`Petitioners request IPR and cancellation of claims 1-20. Petitioners’ full
`
`statement of the reasons for the relief requested is set forth in detail below.
`
`VI. THE ’148 PATENT
`
`The ’148 patent has two independent claims (claims 1 and 12). Independent
`
`claim 1 is directed to a pharmaceutical formulation of amphetamine base salts
`
`comprising an immediate release dosage form and a delayed enteric-release dosage
`
`form, wherein the formulation is sufficient to maintain an effective level of
`
`amphetamine base salts in the patient over at least 8 hours.
`
`In addition, other
`
`limitations of claim 1 recite that the peak plasma concentration of the amphetamine
`
`base salts is higher after the delayed enteric release than after the immediate release,
`
`and that the pharmaceutical formulation contains about a total dosage of 20mg
`
`resulting in a plasma concentration profile with an AUC of 467 ng hr/mL to 714 ng
`
`hr/mL. EX1001, 13:28-55.
`
`Claim 12 is similar to Claim 1, but instead of the total dose and AUC
`
`limitation, Claim 12 recites that the enteric release dosage form comprises a coating
`
`of thickness greater than 20µm “which comprises dried aqueous dispersion of an
`
`6
`
`

`

`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
`
`anionic copolymer based on methacrylic acid and acrylic acid ethyl ester, said
`
`coating being soluble at a pH of about 5.5 upwards.” EX1001 at 14:26-31. A
`
`complete analysis of the claims, as well as application of the relevant prior art is
`
`presented below.
`
`A.
`
`CLAIM CONSTRUCTION
`
`In IPR2015-02009, after considering Petitioner Amerigen’s and Patent
`
`Owner’s arguments, (EX1021), the Board decided the certain terms (provided
`
`below) required explicit construction.
`
`Petitioner Mylan accepts the Board’s
`
`constructions for the purposes of this IPR to the extent that the same or similar term
`
`appears in the ’148 patent:
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`“Pharmaceutically active amphetamine salt(s),” “amphetamine salts,” and
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`“mixed amphetamine salts,”:
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`“Pharmaceutically active amphetamine salts”
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`includes non-salts, such as “amphetamine base” and “methylphenidate,” as well as
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`salts of amphetamine base and methylphenidate. “Amphetamine salt(s)” includes
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`“amphetamine base” and “methylphenidate,” as well as salts of amphetamine base
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`and methylphenidate.
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`“Mixed amphetamine salts” means made up of
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`pharmaceutically active amphetamine salts of more than one kind.
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`Given that “amphetamine base” is included in the Board’s prior construction
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`of “amphetamine salt(s),” Petitioner submits that, “mixture of amphetamine base
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`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
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`salts” and “amphetamine base salts” is included in the construction for
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`“amphetamine salt(s).”
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`With respect to the term “enteric release dosage form” which appears in
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`independent claims 1 and 12 of the ’148 patent, the Board previously determined
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`that “‘enteric release coating’ refers to a coating that will delay release of a drug
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`until the drug has passed through the stomach and reached the intestines.” EX1022
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`at 15. In line with the Board’s prior construction, Petitioner submits that “enteric
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`release dosage form” refers to a dosage form that will delay release of a drug until
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`the drug has passed through the stomach and reached the intestines. EX1022 at 15.
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`With respect to the term “about” (which appears in all claims), “about” should
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`be construed to mean “+20%.” As explicitly stated in the file history: “[t]he term
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`‘about’ has its usual meaning in the field, e.g., roughly + 20%, for example, as used
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`by the FDA in its determinations of bioequivalency.”
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`(EX1035, 4/21/2003
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`Applicant Arguments/Remarks After Final Rejection, US Application No.
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`09/807,462, at p. 5).
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`In Petitioner’s view, all other claim terms should be given their broadest
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`reasonable interpretation in light of the specification of the patent in which they
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`appear. 37 C.F.R. § 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 579 U.S. ___, No.
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`15-446, 2016 WL 3369425, at *14 (2016).
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`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
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`VII. PERSON OF SKILL IN THE ART (“POSA”) & STATE OF THE ART
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`With respect to the ’148 patent, a POSA would have had education and/or
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`experience in the field of drug delivery systems, with knowledge of the scientific
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`literature concerning the same, including some understanding of pharmaceutical
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`formulations for administering amphetamine salts as of 1998. The education and
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`experience levels may vary between persons of ordinary skill, with some persons
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`holding a basic Bachelor’s degree, but with 5-10 years of relevant work experience,
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`or others holding more advanced degrees—e.g., Ph.D.—but having fewer years of
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`experience. A person of ordinary skill may work as part of a multi-disciplinary team
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`and draw upon not only his or her own skills, but also take advantage of certain
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`specialized skills of others in the team, such as those with knowledge of
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`pharmacokinetics, to solve a given problem. Declaration of David Auslander, Ph.D,
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`(EX1002 ¶¶16-19); Declaration of Anthony Palmieri, Ph.D, (EX1029, ¶¶17-20).
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`VIII. IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b))
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`Petitioners respectfully request IPR of claims 1-20 of the ’148 patent on the
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`specific ground of unpatentability outlined below. Per 37 C.F.R. § 42.6(d), copies
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`of the references are filed herewith. In support of the proposed grounds, this Petition
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`includes the declaration of technical experts, David E. Auslander, Ph.D. (EX1002)
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`and Anthony Palmieri, Ph.D, (EX1029), explaining what the art would have
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`conveyed to a POSA as of the priority date.
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`Ground
`1
`
`References
`The ’284 patent in light of the PDR
`1997, Brown, the ’131 patent, and
`Slattum
`
`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
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`Basis
`
`Claims Challenged
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`103
`
`1-20
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`Prior art references in addition to the primary references listed above provide
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`further background in the art, further motivation to combine the teachings of these
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`references and/or further support for why a POSA would have had a reasonable
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`expectation of success to arrive at the invention recited in the challenged claims.
`
`A.
`
`The Scope and Content of the Prior Art
`
`The ’284 Patent
`1.
`U.S. Patent No. 5,837,284 (“the ’284 patent” (EX1005)) entitled “Delivery of
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`Multiple Doses of Medication” was issued on November 17, 1998, from application
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`serial No. 08/892,190, filed on July 14, 1997, and therefore qualifies as prior art
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`under 35 U.S.C. § 102(b) (pre-AIA).1 The ’284 patent was disclosed during
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`prosecution of the ’148 application.
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`The ’284 patent teaches a pharmaceutically active amphetamine salt, i.e.
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`methylphenidate, for treating ADHD, where the dosage form contains “an
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`immediate dosage and a delayed second dosage [which] provides for reduced abuse
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`1 The ’284 patent is 102(b) prior art because of the new matter added to the
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`’148 patent, otherwise, the ’284 patent would be prior art under 102(e).
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`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
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`potential, improved convenience of administration, and better patient compliance,
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`especially when [it] is used to treat certain central nervous system disorders.”
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`EX1005, 1:26-46. The ’284 patent teaches using methylphenidate, “a mild central
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`nervous system stimulant with pharmacological activity qualitatively similar to
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`that of amphetamines,” and its pharmaceutically acceptable salts to treat ADHD.
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`Id. at 2:5-16 (emphasis added).
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`In reference to its release profile, the ’284 patent teaches a formulation
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`comprising immediate release and delayed release enteric dosage forms: “a dosage
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`form containing two groups of particles, each containing the methylphenidate drug.”
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`Id. at 3:3-7. “The two releases can be referred to as ‘pulses’, and such a release
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`profile can be referred to as ‘pulsatile.’” Id. at 5:35-36. “The first group of particles
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`provides a substantially immediate dose of the methylphenidate drug,” while “[t]he
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`second group of particles comprises coated particles [which] provide a delay of from
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`about 2 hours to about 7 hours following ingestion before release of the second
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`dose.” Id. at 3:7-19. This “eliminates the need for a patient, for example a child
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`being treated for ADD, to carry a second dose for ingestion several hours after
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`ingestion of a first dose.” Id. at 5:18-21.
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`Immediate release is “release within about a half hour following ingestion,
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`preferably about 15 minutes, and more preferably within about 5 minutes following
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`ingestion.” Id. at 6:5-8. Delayed release is “a drug release profile which includes a
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`Petition for Inter Partes Review
`of U.S. Patent No. RE 41,148
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`period during which no more than about 10 percent of the drug in a particular dosage
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`form is released, followed by a period of from about 0.5 hour to about 2.5 hours,
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`preferably about 1.5 hours, more preferably about 1 hour, in which no less than about
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`70 percent, preferably no less than about 80 percent, and more preferably no less
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`than about 90 percent, of the drug is released.” Id. at 6:8-16.
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`The ’284 patent also provides a “schematic representation of the plasma
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`concentration of drug resulting from a release profile.” Id. at 5:37-38; Fig. 2. The
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`schematic shows the maximum concentration of two doses (C1and C2), along with
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`their respective ti