In the United States Patent and Trademark Office
`
`Before the Patent Trial and Appeal Board
`
`AMERIGEN PHARMACEUTICALS LIMITED,
`
`Petitioner,
`
`v.
`
`SHIRE LLC,
`
`Patent Owner
`
`U.S. Patent No. 8,846,100 to Shojaei et al.
`Appln. No. 11/383,066, filed May 12, 2006
`Issue Date: September 30, 2014
`
`Title: CONTROLLED DOSE DRUG DELIVERY SYSTEM
`
`
`
`
`
`
`
`______________________
`
`Inter Partes Review No. Unassigned
`______________________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 8,846,100
`UNDER 35 U.S.C. §§ 311-319 AND 37 C.F.R. §§ 42.100 et. seq.
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`
`TABLE OF CONTENTS
`
`TABLE OF CONTENTS ......................................................................................... i
`
`TABLE OF AUTHORITIES ................................................................................. iv
`
`EXHIBIT LIST..................................................................................................... viii
`
`I.
`
`INTRODUCTION. ........................................................................................... 1
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1) . ........................ 2
`
`A. Real Party-In-Interest [37 C.F.R. § 42.8(b)(1)]: ......................................... 2
`
`B. Related Matters [37 C.F.R. § 42.8 (b)(2)]: ................................................. 2
`
`C. Designation of Lead and Back-Up Counsel [37 C.F.R. § 42.8 (b)(3)]: ..... 2
`
`D. Service Information [37 C.F.R. § 42.8(b)(4)]: ........................................... 2
`
`E. Fee Payment and Power of Attorney [37 C.F.R. §§ 42.10(b), 42.103]: ..... 3
`
`III. REQUIREMENTS FOR INTER PARTES REVIEW. .................................. 3
`
`A. Grounds for Standing [37 C.F.R. § 42.104(a)]: .......................................... 3
`
`B. Identification of the Challenge [37 C.F.R. § 42.104(b)]: ........................... 3
`
`1. Relevant Information Regarding the ’100 Patent. .............................. 3
`
`a. Specification. ............................................................................... 4
`
`b. Claims. ........................................................................................ 5
`
`c. Prosecution History. .................................................................... 6
`
`d. Person of Ordinary Skill in the Art. ..........................................14
`
`2. Statement of Precise Relief Requested. [37 C.R.F. § 42.104(b)(1)] 15
`
`– i –
`
`

`

`
`
`3. Specific Statutory Grounds On Which The Challenge Is Based
`And Prior Art References Relied Upon. [37 C.F.R.
`§§ 42.104(b)(2) and (b)(4)] ..............................................................15
`
`4. Challenged Claim Construction. [37 C.F.R. § 42.104(b)(3)] ..........15
`
`IV. DETAILED DESCRIPTION OF THE PRIOR ART UPON WHICH
`THE CHALLENGE IS BASED. ..................................................................19
`
`A. Technology Background. ..........................................................................19
`
`1. Amphetamine Was A Well-Known ADHD Treatment........................19
`
`2. The Science of Drug Coatings, Release Timing, And Release
`Rates Was Well-Known. ....................................................................19
`
`3. “Sculpting The Dose” Was Well-Known. .........................................21
`
`B. Printed Publications Relied Upon. ...........................................................21
`
`1. The ’819 Patent. ................................................................................21
`
`2. The ’300 Patent. ................................................................................23
`
`3. Kratochvil. ........................................................................................25
`
`4. Additional Prior Art Confirming the General Knowledge of the
`Ordinarily-Skilled Artisan. ...............................................................27
`
`V. THE CONSTRUED CLAIMS ARE UNPATENTABLE, 37 C.F.R.
`§ 42.104(b)(4). .................................................................................................28
`
`A. Standard of Invalidity under 37 C.F.R. § 42.104(b)(4). ...........................28
`
`B. Explanation Of Ground 1 For Unpatentability: The ’819 Patent
`Anticipates Each of the 31 Claims of the ’100 Patent. ............................32
`
`1. The ’819 Patent Discloses Every Limitation of Independent Claim
`1. .......................................................................................................33
`
`2. The ’819 Patent Discloses the Modifications to the
`Pharmaceutical Composition of Claim 1 That Are Claimed by
`
`– ii –
`
`

`

`
`
`Dependent Claims 2-4, 13-–21 and Claim 31. .................................37
`
`3. Claims 5–12 are anticipated by the ’819 patent. ..............................43
`
`4. The ’819 Patent Anticipates Claims 22–30. .....................................46
`
`VI. Conclusion. ......................................................................................................60
`
`
`
`
`
`– iii –
`
`

`

`
`
`TABLE OF AUTHORITIES
`
`FEDERAL CASES
`
`Allergan, Inc. v. Apotex Inc.,
` 754 F.3d 925 (Fed. Cir 2014) ..............................................................................28
`
`Bristol-Meyers Squibb Co. v. Ben Venue Labs., Inc.,
` 246 F.3d 1368 (Fed. Cir. 2001) .................................................................... 29, 37
`
`Continental Can Co. U.S.A., Inc. v. Monsanto Co.,
` 948 F.2d 1264 (Fed. Cir. 1991) .............................................................. 28, 46, 59
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) .........................................................................................16
`
`Dayco Prods. Inc. v. Total Containment, Inc.,
`329 F.3d 1358 (Fed. Cir. 2003). ...........................................................................28
`
`Ex parte A,
` 17 U.S.P.Q. 2d 1716 (B.P.A.I. 1990) ........................................................... 30, 43
`
`Graham v. John Deere Co.,
` 383 U.S. 1 (1996) ................................................................................................48
`
`Heartland Tanning, Inc. v. Sunless, Inc.,
`IPR2014-00018,
`2014 WL 1253151 (P.T.A.B., Mar. 13, 2014) ......................................................31
`
`Hybritech Inc. v. Monoclonal Antibodies,
` 802 F.2d 1367 (Fed. Cir. 1986) ...........................................................................29
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ................................................................................ 8
`
`In re Applied Materials, Inc.,
` 692 F.3d 1289 (Fed. Cir. 2012) .................................................................... 47, 60
`
`In re Best,
` 562 F.2d 1252 (C.C.P.A. 1977) .............................................................. 28, 42, 45
`
`– iv –
`
`

`

`
`
`In re Courtright,
` 377 F.2d 647 (C.C.P.A. 1967) .............................................................................43
`
`In re Donohue,
`766 F.2d 531 (Fed. Cir.1995) ...............................................................................42
`
`In re Gleave,
` 560 F.3d 1331 (Fed. Cir. 2009) ...........................................................................29
`
`In re Inland Steel Co.,
` 265 F.3d 1354 (Fed. Cir. 2001) ...........................................................................50
`
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) ..................................................................... 29, 41
`
`In re O’Farrell,
` 853 F.2d 894 (Fed. Cir. 1998) .............................................................................49
`
`In re Paulsen,
` 30 F.3d 1475 (Fed. Cir. 1994) .............................................................................16
`
`In re Petering,
` 301 F.2d 676 (C.C.P.A .1962) ...................................................................... 30, 43
`
`In re Rinehart,
` 531 F.2d 1048 (C.C.P.A. 1976) ...........................................................................48
`
`In re Russell,
`439 F.2d 1228 (C.C.P.A. 1971) .............................................................................. 8
`
`In re Translogic Tech., Inc.,
` 504 F.3d 1249 (Fed. Cir. 2007) ...........................................................................16
`
`In re Van Geuns,
` 988 F.2d 1181 (Fed. Cir. 1993) ...........................................................................16
`
`In re Wood,
` 599 F.2d 1032 (C.C.P.A. 1979) ...........................................................................50
`
`King Pharms., Inc. v. Eon Labs, Inc.,
` 616 F.3d 1267 (Fed. Cir. 2010) ...........................................................................29
`
`– v –
`
`

`

`
`
`KSR Int’l Co. v. Teleflex Inc.,
` 550 U.S. 398 (2007) ............................................................................................48
`
`Macauto U.S.A. v. BOS GmbH & KG ,
`No. IPR2012-00004 (TLG),
`2013 WL 5947694 (P.T.A.B., Jan. 24, 2013) .......................................................32
`
`Merck & Co. v. Biocraft Labs., Inc.,
` 874 F.2d 804 (Fed. Cir. 1989) ...................................................................... 47, 59
`
`Merck & Co. v. Teva Pharm. USA, Inc.,
` 395 F.3d 1364 (Fed. Cir. 2005) .................................................................... 54, 55
`
`Micron Tech., Inc. v. Board of Trustees of the Univ. of Ill.,
`IPR2013-00008,
`2013 WL 5970124 (Mar. 13, 2013) .....................................................................31
`
`Nuvasive, Inc. v. Neurovision Med. Products, Inc.,
`IPR2015-00502,
`2015 WL 4381727 (P.T.A.B., July 16, 2015) .......................................................32
`
`O2 Micro Int’l Ltd. v. Beyond Innovation Tech. Co., Ltd.,
` 521 F.3d 1351 (Fed. Cir. 2008) ...........................................................................16
`
`Perfect Web Techs., Inc. v. InfoUSA, Inc.,
`587 F.3d 1324 (Fed. Cir. 2009) ............................................................................29
`
`Santarus, Inc. v. Par Pharm., Inc.,
` 694 F.3d 1344 (Fed. Cir. 2012) .................................................................... 30, 42
`
`U.S. Surgical Corp. v. Ethicon, Inc.,
` 103 F.3d 1554 (Fed. Cir. 1997) ...........................................................................17
`
`Verdegaal Bros, Inc. v. Union Oil Co. of California,
` 814 F.3d 628 (Fed. Cir. 1987) .............................................................................28
`
`Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc.,
` 200 F.3d 795 (Fed. Cir. 1999) .............................................................................16
`
`– vi –
`
`

`

`
`
`STATE CASES
`
`35 U.S.C. § 102 ................................................................................................ passim
`
`35 U.S.C. § 103 ............................................................................................. 3, 15, 48
`
`35 U.S.C. §§ 311–319 ................................................................................................ 1
`
`STATUTES
`
`37 C.F.R. § 42.8 ......................................................................................................... 2
`
`37 C.F.R. § 42.10 ....................................................................................................... 3
`
`37 C.F.R. § 42.100 ...................................................................................................16
`
`37 C.F.R. § 42.103 ..................................................................................................... 3
`
`37 C.F.R. § 42.104 .................................................................................. 3, 15, 16, 28
`
`
`
`
`
`
`
`– vii –
`
`

`

`
`
`EXHIBIT LIST
`
`Ex. 1001. U.S. Patent No. 8,846,100 (“the ’100 patent”)
`
`Ex. 1002. U.S. Patent No. 6,322,819 (“the ’819 patent”)
`
`Ex. 1003. U.S. Patent No. 6,605,300 (“the ’300 patent”)
`
`Ex. 1004. Original application 11/383,066 (“the ’066 application”)
`
`Ex. 1005. The ’066 application, first preliminary amendment, 10-24-06
`
`Ex. 1006. The ’066 application, second preliminary amendment, 10-26-06
`
`Ex. 1007. The ’066 application, first Office Action, 10-2-09
`
`Ex. 1008. The ’066 application, first Response, 1-29-10
`
`Ex. 1009. The ’066 application, second Office Action, 4-30-10
`
`Ex. 1010. The ’066 application, second Response, 7-28-10
`
`Ex. 1011. The ’066 application, third Office Action, 10-12-10
`
`Ex. 1012. The ’066 application, third Response, 1-12-2011
`
`Ex. 1013. The ’066 application, fourth Office Action, 10-07-13
`
`Ex. 1014. The ’066 application, fourth Response, 1-24-2014
`
`Ex. 1015. The ’066 application, fifth Office Action, 4-30-2014
`
`Ex. 1016. The ’066 application, fifth Response, 6-3-2014
`
`Ex. 1017. The ’066 application, Notice of Allowance and Allowability, 7-7-2014
`
`Ex. 1018. Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`Ex. 1019. Christopher J. Kratochvil, ADHD: Treatment and Outcome,
`MANAGING ADHD, vol. 4 (3A) (2004)
`
`Ex. 1020. C. Bradley, The Behavior of Young Children Receiving Benzedrine,
`AM. J. PSYCHIATRY, vol. 94, 154-162 (1937)
`
`
`
`– viii –
`
`

`

`
`
`EX.
`
`Ex. 1021
`1021
`
`“Adderall,” Drugs@FDA (http://www.accessdata.fda.gov/)
`“Adderall,” Drugs @FDA (http://WWW.accessdata.fda.gov/)
`
`EX.
`
`Ex. 1022
`1022
`
`“Adderall XR,” Drugs@FDA (http://www.accessdata.fda.gov/)
`“Adderall XR,” Drugs @FDA (http: / /Www. accessdata.fda.g0V/)
`
`EX.
`
`Ex. 1023 U.S. Patent No. 6,913,768
`1023 US. Patent No. 6,913,768
`
`EX.
`
`Ex. 1024 U.S. Patent No. 2,738,303
`1024 US. Patent No. 2,738,303
`
`EX.
`
`Ex. 1025 U.S. Patent No. 5,407,686
`1025 US. Patent No. 5,407,686
`
`EX.
`
`Ex. 1026 U.S. Patent Application Publication No. 2004/0197405
`1026 US. Patent Application Publication No. 2004/0197405
`
`EX.
`
`Ex. 1027 U.S. Patent No. 5,837,284
`1027 US. Patent No. 5,837,284
`
`EX.
`
`Ex. 1028 U.S. Patent No. 8,906,413
`1028 US. Patent No. 8,906,413
`
`EX.
`
`Ex. 1029 U.S. Patent No. 6,555,136
`1029 US. Patent No. 6,555,136
`
`EX.
`
`Ex. 1030 U.S. Patent No. 5,326,570
`1030 US. Patent No. 5,326,570
`
`EX.
`
`Ex. 1031 U.S. Patent No. 8,313,776
`1031
`US. Patent No. 8,313,776
`
`EX.
`
`Ex. 1032 U.S. Patent No. 4,728,512
`1032 US. Patent No. 4,728,512
`
`EX.
`
`Ex. 1033 U.S. Patent No. 4,794,001
`1033 US. Patent No. 4,794,001
`
`EX.
`
`Ex. 1034 U.S. Patent No. 4,904,476
`1034 US. Patent No. 4,904,476
`
`EX.
`
`Ex. 1035 U.S. Patent No. 5,474,786
`1035 US. Patent No. 5,474,786
`SURELEASE® Product Brochure
`SURELEASE® Product Brochure
`Ex. 1037 U.S. Patent No. RE42,096
`1037 US. Patent No. RE42,096
`
`EX.
`
`Ex. 1036
`1036
`
`EX.
`
`EX.
`
`EX.
`
`EX.
`
`The ’066 application, Patent Publication No. 2007/0264323
`Ex. 1038
`The ’066 application, Patent Publication No. 2007/0264323
`1038
`Ex. 1039 OPADRY® Manufacturer Poster
`1039
`OPADRY® Manufacturer Poster
`Ex. 1040 Orange Book: Approved Drug Products with Therapeutic
`1040
`Orange Book: Approved Drug Products with Therapeutic
`Equivalence Evaluations: Patent and Exclusivity for: N021303
`Equivalence Evaluations: Patent and Exclusivity for: N021303
`Ex. 1041 Adderall® XR Medication Guide
`1041
`Adderall® XR Medication Guide
`June 2005 Package Insert for Adderall® Immediate Release (“IR”)
`Ex. 1042
`1042
`June 2005 Package Insert for Adderall® Immediate Release (“IR”)
`
`EX.
`
`EX.
`
`—ix—
`
`– ix –
`
`

`

`
`
`Ex. 1043 May 2005 Package Insert for Adderall® Extended Release (“XR”)
`Ex. 1044 The Merck Index, (Susan Budavari, ed., 11th ed., 1996)
`
`Ex. 1045
`
`Susan B Clausen, Single- and multiple-dose pharmacokinetics of an
`oral mixed amphetamine salts extended-release formulation in adults,
`CNS SPECTRUMS vol. 10 (Dec. 2005)
`
`Ex. 1046. Ansel, Popovich & Allen, Pharmaceutical Dosage Forms and Drug
`Delivery Systems (6th ed., 1995)
`Ex. 1047 Adderall® Immediate Release (“IR”) Medication Guide
`Ex. 1048
`Simon J. Tulloch, et al., SLI381 (Adderall XR), a Two-Component,
`Extended-Release Formulation of Mixed Amphetamine Salts:
`Bioavailability of Three Test Formulations and Comparison of Fasted,
`Fed, and Sprinkled Administration, PHARMACOTHERAPY vol. 22
`(2002)
`
`Ex. 1049
`
`Ex. 1050
`
`Ex. 1051
`
`1974: Physicians’ Desk Reference (28th ed., 1974)
`1993 Physicians’ Desk Reference (47th ed., 1992)
`1995 Physicians’ Desk Reference (49th ed., 1994)
`
`Ex. 1052
`
`1997 Physicians’ Desk Reference (51st ed., 1997)
`
`
`
`Ex. 1053
`
`Patricia K. Sonsalia, Remington: The Science and Practice of
`Pharmacy (19th ed., 1995)
`
`Ex. 1054 Brian B. Hoffman & Robert J. Lefkowitz, Goodman & Gilman’s The
`Pharmacological Basis of Therapeutics (9th ed., 1996)
`
`
`Ex. 1055 Charles S. L. Chiao & Joseph R. Robinson, Remington: The Science
`and Practice of Pharmacy (19th ed., 1995)
`
`Stuart C. Porter, Remington: The Science and Practice of Pharmacy
`(19th ed., 1995)
`
`1995 United States Pharmacopeia and National Formulary, USP 23-
`NF (1994)
`
`Ex. 1056
`
`Ex. 1057
`
`
`
`– x –
`
`

`

`
`
`Ex. 1058 W. H. Hartung & J. C. Munch, Amino Alcohols, VI. The Preparation
`and Pharmacodynamic Activity of Four Isomeric
`Phenylpropylamines, 53 J. AM. CHEM. SOC. (1931)
`
`Ex. 1059 Handbook of Pharmaceutical Excipients (Ainley Wade & Paul J
`Weller, ed., 2d ed., 1994)
`
`Ex. 1060
`
`Ex. 1061
`
`James R. McCowan, Dispensing of Medication (Eric W. Martin ed.,
`7th ed., 1971)
`Edward Stempel, Dispensing of Medication, (Eric W. Martin ed., 7th
`ed., 1971)
`
`Ex. 1062 U.S. Patent No. 1,879,003
`
`Ex. 1063 U.S. Patent No. 1,921,424
`
`Ex. 1064 Charles W. Popper, M.D., The Story of Four Salts, JOURNAL OF CHILD
`AND ADOLESCENT PSYCHOPHARMACOLOGY vol. 4, n. 4 (1994)
`
`Ex. 1065 Approval Letter from Robert Temple, M.D., Director, Office of Drug
`Eval., to William A. Nuerge, Chief Oper. Officer, Richwood Pharm.
`Co., Inc. (Feb. 13, 1996) (on file at
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/11522S010_A
`dderall.pdf)
`
`Ex. 1066 Approval Letter from Russell Katz, M.D., Director, Div. of
`Neuropharm. Drug Products, Office of Drug Eval., to Tami Martin,
`Vice Pres. of Reg. Affairs, Shire Labs., Inc. (Oct. 11, 2001) (on file at
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21303_Add
`erall_Approv.pdf)
`
`Ex. 1067 April 21, 2003 Resp. to Office Action dated March 4, 2003, App. No.
`09/807,462
`
`– xi –
`
`

`

`
`
`I.
`
`INTRODUCTION.
`
`Amerigen Pharmaceuticals Limited requests inter partes review under
`
`35 U.S.C. §§ 311–319 of claims 1–31 of U.S. Patent No. 8,846,100 (“the ’100
`
`patent,” Ex. 1001).
`
`The ’100 patent claims a pharmaceutical composition containing three
`
`different beads of amphetamine salts: (1) a bead for immediate release, (2) a bead
`
`for delayed and pulsed release, and (3) a bead for delayed and sustained release.
`
`The ’100 patent contains just one example of each of these beads. See Ex. 1018
`
`¶ 70. Each of these beads, however, is not new in any way – the exact same
`
`amphetamine-containing beads (immediate, delayed pulsed, and delayed sustained
`
`release) were literally duplicated from examples in U.S. Patent No. 6,322,819 (“the
`
`’819 patent,” Ex. 1002) and U.S. Patent No. 6,605,300 (“the ’300 patent,” Ex.
`
`1003). Including these three amphetamine-containing beads in a single
`
`pharmaceutical formulation is not new or novel because such inclusion is explicitly
`
`contemplated by the ’819 and ’300 patents. Although the ’300 patent was
`
`discussed during the prosecution of the ’100 patent, the Applicant made factually
`
`incorrect statements about the ’300 patent in an effort to distinguish the reference,
`
`which materially affected the course of prosecution and warrants additional
`
`consideration by the Board.
`
`– 1 –
`
`

`

`
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1) .
`
`A. Real Party-In-Interest [37 C.F.R. § 42.8(b)(1)]:
`
`The real party-in-interest is Amerigen Pharmaceuticals Limited
`
`(“Amerigen” or “Petitioner”).
`
`B. Related Matters [37 C.F.R. § 42.8 (b)(2)]:
`
`There are no judicial matters that would affect, or be affected by, a decision
`
`in the proceeding. Related pending patent applications include U.S. Patent
`
`Application No. 14/790,446. Related issued patents include U.S. Patent
`
`No. 9,173,857.
`
`C. Designation of Lead and Back-Up Counsel [37 C.F.R. § 42.8
`(b)(3)]:
`
`Lead counsel is Marc R. Wezowski (Reg. No. 73,825) and back-up counsel
`
`is Philip D. Segrest, Jr. (Reg. No. 39,021).
`
`D. Service Information [37 C.F.R. § 42.8(b)(4)]:
`
`Papers concerning this matter should be served on the following:
`
`Mail and hand-delivery address:
`
`Marc R. Wezowski
`HUSCH BLACKWELL LLP
`120 S. Riverside Plaza, STE 2200
`Chicago, Illinois 60606
`
`
`
`E-mail: Marc.Wezowski@huschblackwell.com with a cc to
`Philip.Segrest@huschblackwell.com
`
`– 2 –
`
`

`

`
`
`
`
`Telephone: (312) 622-1500
`Facsimile: (312) 622-1501
`Petitioner consents to service by email at:
`
`Marc.Wezowski@huschblackwell.com and Philip.Segrest@huschblackwell.com.
`
`E. Fee Payment and Power of Attorney [37 C.F.R. §§ 42.10(b),
`42.103]:
`
`The Office is authorized to charge petition fees and deficiencies to Deposit
`
`Acct. No. 23-0920, Cust. ID No. 24628. A Power of Attorney is being filed
`
`concurrently.
`
`III. REQUIREMENTS FOR INTER PARTES REVIEW.
`
`A. Grounds for Standing [37 C.F.R. § 42.104(a)]:
`
`Petitioner certifies that the ’100 patent is available for inter partes review
`
`and that Petitioner is not estopped or barred from requesting inter partes review of
`
`the ’100 patent on the grounds identified herein.
`
`B.
`
`Identification of the Challenge [37 C.F.R. § 42.104(b)]:
`
`Petitioner requests inter partes review of claims 1–31 of the ’100 patent and
`
`asks that those claims be found unpatentable under 35 U.S.C. § 102 and/or § 103.
`
`1. Relevant Information Regarding the ’100 Patent.
`
`The ’100 patent issued September 30, 2014, from Application No.
`
`11/383,066, with a filing date of May 12, 2006. Ex. 1018 ¶ 23.
`
`– 3 –
`
`

`

`
`
`a.
`
`Specification.
`
`The ’100 patent relates to a multiple dose composition for pharmaceutically
`
`active amphetamine salts pertaining to the treatment of Attention Deficit
`
`Hyperactivity Disorder (ADHD). Ex. 1018 ¶ 58. The Background section
`
`describes various drug delivery systems for immediate, constant, sustained, pulsed,
`
`and delayed release are described. Ex. 1001, 1:53-3:49. Adderall® is an
`
`immediate-release (IR) mixture of amphetamine salts (“MAS”):
`
`dextroamphetamine sulfate; dextroamphetamine saccharate; amphetamine
`
`aspartate monohydrate; and amphetamine sulfate. Ex. 1018 ¶¶ 71–72; Ex. 1001,
`
`3:6–10. Adderall® XR an extended release version that can be administered once
`
`daily instead of twice daily as needed for immediate release Adderall®. Ex. 1001,
`
`3:13–25; Ex. 1018 § 193. Adderall® XR and another drug, Concerta®
`
`(methylphenidate), last up to twelve hours, but the effect can be extended further
`
`by later administering an IR dose of the same medication . Ex. 1001, 3:31–41.
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`The ’100 patent describes a drug delivery system with a core and coating
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`layers (each of which may or may not be loaded with drug) and/or a layer that
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`controls the onset and characteristics of the drug release. Ex. 1018 ¶ 60–61;
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`Ex. 1001, 12:64–13:10. Example 1 describes an immediate release formulation
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`bead, and the other Examples, namely Examples 2–4, describe various delayed
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`release beads. Ex. 1018 ¶¶ 62–68; Ex. 1001, 18:50–21:34. Figure 3 illustrates a
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`– 4 –
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`capsule containing an immediate release bead and two delayed release beads,
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`which is also described in Examples 5–7. Ex. 1018 ¶¶ 69–70; Ex. 1001, 21:35–
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`22:67. Examples 8–10 describe pharmacokinetic studies. Id., 23:1–31:67.
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`b. Claims.
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`Independent claim 1 recites a pharmaceutical composition comprising an
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`immediate release bead comprising at least one amphetamine salt, a first delayed
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`release bead comprising at least one amphetamine salt, and a second delayed
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`release bead comprising at least one amphetamine salt. Ex. 1001, 31:59–63; See
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`Ex. 1018 ¶ 50. The claim further recites that the first delayed release bead
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`provides pulsed release of the at least one amphetamine salt and the second
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`delayed release bead provides sustained release of the at least one amphetamine
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`salt. Ex. 1001, 31:63–67. The claim also recites that the second sustained release
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`bead comprises at least one amphetamine salt layered onto or incorporated into a
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`core, a delayed release coating layered onto the amphetamine core, and a the
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`sustained release coating layered onto the delayed release coating, where the
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`sustained release coating is pH-independent, and the first and second delayed
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`release beads comprise an enteric coating. Id., 32:29–37.
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`Claims 2–4 add that the enteric coating is pH-dependent and that the
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`different beads comprise different enteric coatings or the same enteric coatings,
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`respectively. Ex. 1001, 32:38–45; Ex. 1018 ¶ 51. Claims 5–12 recite certain
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`– 5 –
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`pharmacokinetic features of the claimed bead combination. Ex. 1001, 32:46–
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`33:14; Ex. 1018 ¶ 51. Claims 13–18 add that the immediate release bead and the at
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`least one delayed release bead are on the same core or are on different cores, that
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`the amphetamine salt is coated onto a core or incorporated into a core, and that
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`there is a protective layer over at least one enteric coating, or that there is a
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`protective layer between the amphetamine salt and at least one enteric coating,
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`respectively. Id., 32:15–30. Claims 19–20 recite the inclusion of one or more
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`specific amphetamine salts. Ex. 1001, 33:31–34:7. Claim 21 specifies the lack of
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`a food effect. Id., 34:8–9. Claims 22–30 recite the amount of amphetamine salt
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`that is present in the dosage form. Id., 34:10–27. Claim 31 recites a protective
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`coating layered between the delayed release coating and the sustained release
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`coating. Id., 34:28–31.
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`Prosecution History.
`c.
`The ’100 patent was submitted as application serial no. 11/383,066 (“the
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`’066 application,” Ex. 1004) on May, 12, 2006, with 58 claims. Ex. 1003, 1; 48–
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`55. Two preliminary amendments were filed, cancelling claims 33–58, and adding
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`new claims 59–61. Ex. 1005; Ex. 1006. The first Office Action rejected all of the
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`claims as anticipated and/or rendered obvious by the ’300 patent stating that “the
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`’300 patent teaches an oral pulsed release formulation comprising a combination of
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`immediate release and delayed release amphetamine beads.” Ex. 1007 p.4. The
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`– 6 –
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`Action further stated regarding the ’300 patent disclosure:
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`The formulation can comprise a coated core comprising an immediate
`release portion of the amphetamine salts, along with an enterically
`coated delayed release bead (claim 1). The enteric polymers include
`pH dependent enteric polymers (col. 8, lin. 43–68); the formulation
`further comprises a protective coating to the core between the drug
`layers, or at the enteric layer (col. 8, lin. 10–30). The amphetamine is
`coated to an inert seed material (Example 1). This coated seed is then
`coated with various polymers, forming a core with the amphetamine
`incorporated (Examples 2 and 3). The formulation can comprise
`multiple coated delayed core comprises [sic] different enteric
`polymers or the same polymers such as Eudragit L or 4110D
`(Examples 1–4). The formulation comprises a combination of
`immediate release beads and controlled release beads (Example 4).
`The formulation can comprise up to 20 mg of a mixture of
`amphetamine salts … A single immediate release bead can be coated
`with a delayed release bead coating solution and combined with a
`second delayed release formulation so that the immediate and delayed
`release portions are present in the same bead and on different beads
`(Example 4).
`
`Id. p.4–5. The Action stated that the physiological effects of the dosage
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`form (food, Tmax, AUC, and Cmax values) “are merely functional limitations
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`that are the result of the instant compositional components,” which are
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`“inherent properties of the composition … since a compound and its
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`properties cannot be separated.” Id. p.5 (emphasis added). Speaking to a
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`– 7 –
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`37.5 mg dose, the Action stated that these limitations “merely recite a future
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`intended use for the composition.” Id. p.5 (emphasis added).
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`The Action also rejected all the claims as obvious in view of the ’300 patent
`
`stating that “the ’300 patent discloses a controlled release dosage form comprising
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`immediate release bead sand [sic] delayed release beads where the delayed release
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`beads comprise enter[ic] polymers and protective coating.” Id. p.6. The Action
`
`noted that the ’300 patent teaches amphetamine salts at a concentration of at least
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`20 mg and that increasing the dosage of a well-known pharmaceutical dependent
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`upon the patient is well within the limits of a person skilled in the art. Id. The
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`Action further stated that because the general claim conditions were met, it was not
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`inventive to discover the optimum ranges by routine experimentation, citing In re
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`Aller, 220 F.2d 454 (C.C.P.A. 1955) and In re Russell, 439 F.2d 1228 (C.C.P.A.
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`1971). Ex. 1007 p.6–7.
`
`In response, the Applicant argued that “[t]he ’300 patent discloses immediate
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`release beads and delayed pulsed release beads, but not sustained release beads.”
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`Ex. 1008 p.8 (emphasis added); see also id., 9 (“The ’300 patent does not disclose
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`a sustained release bead.”). However, this statement is not true and is a clear
`
`mischaracterization of the ’300 patent.
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`The ’066 application describes what is meant by a “sustained release bead”:
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`a “sustained release formulation of the present invention comprises at least one
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`– 8 –
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`amphetamine salt layered onto, or incorporated into, a core; a delayed release
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`coating layered onto the amphetamine core; a sustained release coating layered
`
`onto the delayed release coating; and, optionally, a protective coating.” Ex. 1004
`
`p.9. The ’066 application states that the delayed pulse release component can
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`include an enteric coating and provides a list of enteric coatings including
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`EUDRAGIT® L30D-55 and EUDRAGIT® 4110D. Id. p.22–23. The ’066
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`application further states that the sustained release coating is a polymer or
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`combination of polymers and provides a list of suitable polymers, including
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`SURELEASE®. Id. p.23.
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`Example 4 of the ’300 patent derives from Examples 1–3. Ex. 1003, 10:32–
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`12:26. Example 1 discloses an immediate release bead made of amphetamine salts
`
`layered onto a core; Examples 2 and 3 disclose delayed release beads having an
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`enteric coating applied over the sustained release bead of Example 1. Example 4
`
`adds a sustained release coating of SURELEASE® and a coating of OPADRY®
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`over the beads of Examples 2 or 3. Thus, Example 4 discloses an immediate
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`release bead covered by layers of a delayed release coating, a sustained release
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`coating, and an OPADRY® coating, respectively. Id.
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`The Applicant further misconstrued the teachings of the ’300 patent by
`
`arguing that the ’300 patent teaches that “a pulsed dose delivery system … is
`
`something to be used in place of a sustained release preparation.” Ex. 1008 p.8.
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`– 9 –
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`

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`This is not what the ’300 patent states in the referenced passage, which is, in
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`reality, a general discussion of the problems associated with prior art systems. Ex.
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`1003, 1:13–2:12.
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`Further mischaracterizing the art, the Applicant represented that “the ’300
`
`patent teaches that sustained release [beads] do not work for amphetamines.”
`
`Ex. 1008 p.9. The Applicant did not provide a citation as to where the ’300 patent
`
`stated such, but instead argued that there were problems with sustained release
`
`amphetamine formulations, without citing the ’300 patent. Id.. The Applicant
`
`stated that “the ’300 patent teaches: (1) not to use sustained release amphetamine
`
`formulations and (2) to use a delayed pulsed release formulation instead,” without
`
`citing the ’300 patent. Id.
`
`In the second Office Action (Ex. 1009), the Action maintained the
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`anticipation and obviousness rejections stating that the formulation of the ’300
`
`patent comprises the same immediate and delayed release beads, the same
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`polymers, and the same arrangement of the formulation such that the formulations
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`must also have the same bioequivalence and blood plasma concentrations. Id. p.4.
`
`The Action stated that that the ’300 patent teaches a dosage form comprising a
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`plurality of beads including immediate release beads and coated controlled release
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`beads. Id. p.7. The Action further stated that since the ’300 patent discloses
`
`multiple beads, both immediate release uncoated beads and enteric coated beads,
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`– 10 –
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`the claims remain fully anticipated and obvious. Id. The Action mentioned that
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`Figure 3 of the ’066 application discloses a sustained release formulation achieved