.19) United States
`C
`(12) Reissued Patent
`Burnside et al.
`
`(10) Patent Number:
`(45) Date of Reissued Patent:
`
`US RE42,096 E
`Feb. 1, 2011
`
`USO0RE42096E
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`424 477
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`I
`424.149’?
`4245459
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`(75)
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`Inventors: Beth A. Burnside. Betliesda. Ml) (U23):
`Xiaodi Gun, Apex. NC (US); Kimberly
`Figske. Downjnglow, PA (US); Richard
`r\-Couch-B13/11M«'|Wr-PA (US);
`Rong-Kun Chang. Rockville. MD (US):
`Donald .l. Treacy. Woodbine. MI ) (US):
`Charlotte M. Mcfluiness. Bethesda.
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`Related U.S. Patent Documents
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`Reissue of:
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`A multiple pulsed dose drug delivery system for pharmaceu-
`tically active amphetamine salts. comprising an imniediate—
`release cornpoiieiit and an1enterie delayed-release compo-
`nenlv wherein (1) the enlerie release coating has a detined
`minimum thickness andfor (2) there is a protective layer
`between the pharmaceutically active amphetamine salt and
`the eiiteric release coating andfor (3) there is a protective
`layer over the enlerie release coating. The product can be
`eoinposed of either one of a number of heads in a dosage
`form. including either capsule. tablet. or sachet method for
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`

`
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`
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`(2005),
`164- 166.
`
`Sprowls’ American Pharmacy: An I11troduction to Phanna—
`ceutical Techniques a11d Dosage Forms, 7th Ed. (1974),
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`Tl1e Merck Index: Atnpltetannine, 12111 l.id., 620.
`The Merck lt1dex: Ainphetaniine. 13th 1id.. (2001 ), 97. 1089.
`The United States Pharnlacopeia 23, National Forntulary 18
`(1995) pp. 1791-1799.
`The United States Pharniacopeia 26, National l"orn1u1ary 21
`(2003) pp. 2157 2155.
`The United States Pharinacopeia 27, National l"orn1ulary 22
`(2004) pp. 2302-2312.
`Answering Expert Report of Dr. Alexander Klibanov. Apr.
`25, 2005.
`Answering Iixpert Report of Robert I.,anger. Apr. 25, 2005.
`Expert Report of Dr. Joseph R. Robinson and exhibits
`thereto, Feb. 28, 2005.
`Expen Report of the Honorable Gerald J. Mossinghoff a11d
`exhibits thereto, Mar. 16, 2005.
`Impax laboratories, Inc.‘s lVIen1orandu1n in Snppon of the
`Motion to Amend its Answer dated Feb. 25. 2005 and exhib-
`its thereto.
`
`In1pax Laboratories, Inc.’s Reply Memorandum in Support
`Olilllt: Motion to A111e11d its Answer dated Mar. 18. 2005 and
`exhibit tl1ereto.
`In1pax Laboratories, h1c.’s First Supplemental Responses to
`Shire Laboratories Inc.’s First Set of I11terrogatories (Nos.
`11-12).
`Opening lixpert Report of Dr. Michael Mayersohn a11d
`exhibits thereto, Mar. 12. 2005.
`Opening Expert Report ofDr. Walter Cha111bliss and exhibits
`thereto. Mar. 15. 2005.
`Coucl1 Deposition Transcript. Sep. 8. 2004.
`l"iske Deposition Transcript. Sep. 17, 2004.
`Guo Deposition Transcript, Jul. 26, 2004.
`lV1c(:1uincss Deposition 'I'ranseript, Aug. 6. 2004.
`Rudnic Deposition Transcript, Jul. 28, 2004.
`Chang Deposition Transcript, Sep. 8. 2004.
`Burnside Deposition Transcript, Feb. 2, 2005.
`Treacy Deposition Transcript. Aug. 31. 2004.
`
`IIan'ington Deposition Transcript. Jul. 27, 2005.
`Schaffer Deposition Transcript, Aug. 17. 2005.
`Burnside Deposition Transcript. Feb. 3. 2005.
`Guo Deposition Transcript. Ja11. 24, 2005.
`Chang Deposition Transcript, Jan. 20, 2005.
`Adderall XR Package Inset, Sep. (2004).
`Freedoni of [11 fonnation Request Results for Dexadrine
`(Sn1itl1K1ine l3eecl1am): May 20, 1976 Disclosable Approval
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`I-‘orrns: Development,
`livaluatioii. and Application of In
`Vitrofln Vivo Correlations (1997).
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`Bioequivalence Studies (2002).
`Guidance for
`Industry: SUPAC-MR: Modified Release
`Solid Oral Dosage Forrns (1997).
`Holt, Iiioeqnivalence Studies ofKetoprofen: Product for'n1u-
`latio11. Phannaeokinetics, Decoiwolution, and In Vitro I11
`Wvo correlatio11s_. Thesis submitted to Oregon State Univer-
`sity. Aug. (1997).
`'l'e\ra Notice letter: 1"eb. 21, 2(l05.
`Teva Notice letter: Jun. 1. 2005.
`P] )l{ Drug Information for Ritalin l.A Capsules, Apr.
`(2004).
`Prescribing Iniormation: Dexedrine. brand ofdextroa111pl1et—
`amine sulfate (2001).
`Shire Laboartories lnc.’s Opposition to Barr Laboratories’
`Motion to Amend Its Answers and Counterclainis, Sep. 15,
`2004.
`
`Notice of Allowance U.S. Appl. No. 111091 ,010 filed dated
`Dec. 22, 2008.
`Interview Surnnlary U.S. Appl. No. 1l1"09l.010 filed date
`Dec. 22. 2008.
`
`Wigal, et al., Evaluation of Individual Subjects in the Analog
`Classroom Setting:
`II. Eifects of dose of amphetamine
`(Adderall), Psychopharrnacology Bulletin. vol. 34. No. 4.
`pp. 833 838. 1998.
`Judgn1ent and Order of Permanent [t1jut1ctio11 i11 Shire I..[.C
`V. Teva Phannaceutical Industries Ltd. in the United States
`
`District Court for the Eastern District of Pennsylvania, Civil
`Action No. 06-952-SD. Mar. 6. 2008.
`
`Notice of Allowance i11 U.S. Appl. No. 1 17091.01 1 dated Jul.
`20, 2007.
`Petition to Wit.hdl‘aw Application fronl Issue Pursuant to 37
`CFR l.3l3(c)(2) dated Oct. 16. 2007.
`Transcrip of Richard A. Couch 30(b)(6) Deposition i11 Sl1ire
`I.I.C vs. Sandor. Inc. in the United States District Court for
`the District of Colorado. Dec. 14. 2007.
`
`Transcript ol‘ Beth A. Burnside Deposition in Shire I.I.C vs.
`Sandoz I11c. in the United States District Court for the Dis-
`trict of Colorado. Case No. 07—CV—00]]97-EWN-CBS.
`Nov. 30, 2007.
`'I‘ranscript of Kimberly liiske l"arrand Deposition in Shire,
`I.I.C V. Sandoz. Inc. in the United States District Court of
`Colorado, Dec. 4, 2007.
`Defendant Sandoz, Inc.‘s Answers and Objections to Plain-
`tiff Shire LLC’s 1t1terrogatories (No. 1-9). in the United
`States District Court for the District ol‘ Colorado, Case No.
`07 CV 001197 IEWN CBS, Jun. 18, 2007.
`Defendant Sandoz. Inc.’s Answers and Objections to Plain-
`tiff Sl1ire LLC’s Second Set of Interrogatories (No. 10-19),
`in the United States District Court for the District of Colo-
`rado. Case No. 07 CV 001 197 l:7.WN- C135. Nov. 20, 2007.
`
`Amerigen Ex. 1037, p. 4
`Amerigen Ex. 1037, p. 4
`
`

`
`US RE42,096 E
`Page 5
`
`Defendant Sande’/._. l11c.’s Answers and Objections to Plain-
`tiITSl1i1'L‘ I.I.C’s Second Set of Interflogatories (No. 20 25)
`and Supplement to Answers to lnterrogatories 8 and 9. in the
`United States District Court for the District of Colorado.
`Case No. 07 CV 001197 IQWN CBS. Dec. 10. 2007.
`
`Expert Report of AJ1hu1' J. Steiner in Shire I,I.C V. Colony
`Pllarniaceutieals, lru:., in the United States l)isLrit::l Court for
`the District of Maryland. case No. 1:07—cv—007"l8. Dec. 20,
`2007.
`
`lixpert Report of Ilarry Cr. Hrittain. Phl).
`Supplemental
`1" RSC i11 Shire I.[.C V. Colony I-‘liarmaceuticals, Ine., in the
`United States District Court for the District of Maryland,
`Case No. l:07—cv—00718. Feb. 15.2008.
`Ozturk et al.. “Kinetics of Release from Enteric—Coated Tab-
`lets." Pltarmaeutieal Research l988:5:550 565.
`(iliebre Sellassie et ., “I'7.val1tation oliacrylic based modifie-
`d—release film coatings.” International Journal of Pharrna—
`ceutics. 1987:?-72211-218.
`Order and Memorandtnn Denying Colony's Motion for Par-
`tial Surninary Judgment ol‘Noninli'ingement oi‘ tl1e ‘S I 9 and
`’3(l0 Patents ir1 Shire I.[.C V. Colony l-’l1ar1naeeutit.:als. Ine.,
`in the United States District Court for the District of Mary-
`la11d. Case No. CCB—07—7"18. Jan. 2. 2008.
`I3
`I
`I-’laintilTSl1.ire I.I.(,"s Responses to Interrogatories No.
`ir1 Shire [..l..C V. Colony Pliarrnaceutieals. Inc.. in the United
`States District Court for the District ofMaryland_. Case No.
`l:07—cv—007"1 8—CC B. Jun. 6. 2007.
`Transcript of Richard A. Couch Deposition in Shire LLC v.
`Colony l-’l1armat.:euticals, Il'lt.:., in the United States District
`Cotu't
`liar
`the District
`of Maryland. Case No.
`1:O7—cV—0'07l 8—CC B, Nov. 15, 2007.
`
`Transcript of Beth A. Burnside Deposition in Shire LLC V.
`Colony Pharmaceuticals, Inc._. in the United States District
`Court
`for
`the District
`of Maryland. Case No.
`l:0'z"—cv—0O718—CC B. Nov. 9, 2007.
`
`Transcript of richard Rong—Kun Chang in Shire LLC v.
`Colony Pharmaceuticals, Inc._. in the United States District
`Court
`For
`the
`|:)i5l.rict
`oli Maryland, Case No.
`1:07 (:V- 00718 CCB. Nov. 20. 2(l'07.
`
`liifringernerit and
`Second Amended Complaint for Patent
`Declaratory Relief in Shire Laboratories. Ir1c. v. Andrx Phar-
`maceuticals. LLC. in the United States District Court for the
`Southem District of Florida, Miami Division. Case No.
`07 -22201 CIV Cooker'l3rovv‘n. Nov. 15.2007.
`
`luc. V.
`Answer and Counterelaims in Shire l.aboratories.
`Andrx. LLC.
`in the United States District Court for the
`Southem District of Florida. Miami Division. Case No.
`07—2220l—CIV—Cooke.='Brown, Aug. 31. 2007'.
`
`Plaintifis Shire Laboratories. Inc.’s and Shire LLC’s Reply
`to Defendant Andrx Pharmaceuticals. LLC’s Counterclaims,
`in the United States District Court for the Southern District
`of Florida. Miami Division. Case No. 07 22201 CIV’
`Cool(eJ'I3mwn. Sep. 24. 2007.
`
`Judgment and Order of Permanent Injuunction ir1 Shire
`Laboratories. Inc. v. Andrx Pharmaceuticals. LLC.
`in the
`United States District Court for the Southern District of
`Florida, Miami Division. Case No. 07"—22201—C]V—Cooker‘
`Brown. Nov. 19. 2007.
`
`* cited by examiner
`
`Amerigen Ex. 1037, p. 5
`Amerigen Ex. 1037, p. 5
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`

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`U.S. Patent
`
`Feb. 1, 2011
`
`Sheet 1 of8
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`US RE42,096 E
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`24
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`20
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`12
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`
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`TIME(HOURS)
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`
`Amerigen Ex. 1037, p. 6
`Amerigen Ex. 1037, p. 6
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`

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`U.S. Patent
`
`Feb. 1, 2011
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`US RE42,096 E
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`F-lG.2A
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`Drug
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`Seed Core
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`Amerigen Ex. 1037, p. 7
`Amerigen Ex. 1037, p. 7
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`

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`U.S. Patent
`
`Feb. 1, 2011
`
`Sheet 3 of 3
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`US RE42,096 E
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`Amerigen Ex. 1037, p. 8
`Amerigen Ex. 1037, p. 8
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`

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`Feb. 1, 2011
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`US RE42,096 E
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`Amerigen Ex. 1037, p. 9
`Amerigen Ex. 1037, p. 9
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`

`
`U.S. Patent
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`Feb. 1, 2011
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`Sheet 5 M8
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`US RE42,096 E
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`
`Amerigen Ex. 1037, p. 10
`Amerigen Ex. 1037, p. 10
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`US. Patent
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`Feb. 1,2011
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`US RE42,096 E
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`Amerigen Ex. 1037, p. 11
`Amerigen Ex. 1037, p. 11
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`Feb. 1,2011
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`US RE42,096 E
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`Amerigen Ex. 1037, p. 12
`Amerigen Ex. 1037, p. 12
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`Feb. 1, 2011
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`US RE42,096 E
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`Amerigen Ex. 1037, p. 13
`Amerigen Ex. 1037, p. 13
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`US RE42,096 E
`
`1
`ORAL PULSICD DOSE DRUG DELIVERY
`SYSTEM
`
`Matter enclosed in heavy brackets [ ] appears in the
`original patent but forms no part of this reissue specifica-
`tion; matter printed in italics indicates the additions
`made by reissue.
`This invention pertains to a multiple dosage form deliv-
`ery system comprising one or more amphetamine salts for
`administering tl1e amphetamine salts to a recipient.
`
`BACKGROUND OF THE INVENTION
`
`Traditionally. drug delivery systems have focused on
`constantrsustained drug output with the objective of 1nini—
`mizing peaks and valleys of drug concentrations in the body
`to opt imime drug efficacy and to reduce adverse effects. A
`reduced dosing frequency and improved patient compliance
`can also be expected for tl1e controlledJ'sustained release
`drug delivery systems. compared to immediate release
`preparations. However. for certain drugs, sustained release
`delivery is 11ot' suitable and is affected by tl1e following fac-
`tors:
`
`l’irst pass metabolism: Some drugs. such as B blockers.
`[3—estradiol_. and salicylamide. undergo extensive first pass
`metabolism and require fast drug input to saturate metabo-
`lizing enzymes in order to minimize pre-systemic n1etabo-
`lism. Thus. a constaJ1tr"sustained oral method of delivery
`would result i11 reduced oral bioavailability.
`Biological tolerance: Continuous release drug plasma
`profiles are often accompanied by a decline in the pharmaco-
`therapeutic effect of the drug. e.g.. biological tolerance of
`transdermal nitroglycerin.
`(hronopharmacology and circadian rhyttuns: Circadian
`rhythms in oertain physiological functions are well estab-
`lished. It has been recognized that many symptoms and
`onset of disease occur during specific time periods of the 24
`hour day. e.g.. asthma and angina pectoris attacks are most
`frequently in the morning hours (1 .2).
`Local therapeutic need: For the treatment of local disor-
`ders such as inflammatory bowel disease, the delivery of
`compounds to the site of mfiammation with no loss due to
`absorption in the small
`intestine is highly desirable to
`achieve the therapeutic elfect a11d to minimize side effects.
`Gastric irritation or drug instability in gastric fluid: For
`compounds with gastric irritation or chemical instability i11
`gastric fluid. the use of a sustained release preparation may
`exacerbate gistric irritation and chemical instability ir1 gas-
`Lric fluid.
`
`It]
`
`20
`
`r-.i an
`
`30
`
`45
`
`Drug absorption differences in various gastrointestinal
`segrnents: ln general. drug absorption is moderately slow iii
`the stomach. rapid hi the small intestine. and sharply declin-
`ing in the large intestine. Compensation for changing
`absorption characteristics in the gastrointestinal tract may be _
`important for some drugs. For example. it is rational for a
`delivery system to pump out the drug 111uch faster when the
`system reaches the distal segment of the intestine. to avoid
`the entombment of the drug in the feces.
`Pulsed dose delivery systems. prepared as either single
`unit or multiple ttllil formulations, a11d which are capable of
`releasing the drug after a predetermined time. have been
`studied to address the aforementioned problematic areas for
`sustained release preparations. These same factors are also
`problematic in pulsed dose formulation development. For
`example, gastrointestinal transit times vary not only from
`patient‘ to patient but also within patients as a result of food
`
`Gt"!
`
`65
`
`2
`
`intake. stress. and illness; thus a single-unit pulsed-release
`system may give higher variability compared to a multiple
`unit system. Additionally. drug layering or core making for
`multiple unit systems is a time—consun1ing and hard—to—
`optimize process. Particularly challenging for formulation
`scientists has been overcoming two conflicting hurdles for
`pulsatile formulation development, i.e.. lag time and rapid
`release.
`
`Various enteric materials. e.g.. cellulose acetate phthalate.
`hydroxypropyl methylcellulose phthalate. polyvinyl acetate
`phthalate. and the |iIJl)R./\(il'l"tl§l- acrylic polymers. have
`been used as gastroresistant. enterosoluble coatings for
`single drug pulse release in the intestine (3). The enteric
`materials. which are soluble at higher pH values. are fre-
`quently used for colon-specific delivery systems. Due to
`their pl]-dependent attributes and the uncertainty of gastric
`retention time.
`in—vivo performance as well as inter— and
`intra—subject variability are major issues for using enteric
`coated systems as a time-controlled release of drugs.
`A retarding swellable hydrophilic coating has been used
`for oral delayed release systems (4.5). It was demonstrated
`that lag time was linearly correlated with coating weight
`gain and drug release was pH independent.
`Hydroxypropyl methylcellulose barriers with erodible
`andfor gellable characteristics formed using press coating
`technology for tablet dosage forms have been described to
`achieve tin1e—progrannned release of drugs (6). Barrier for-
`mulation variables. such as grade of hydroxypropyl
`methylcellulose. water—soluble and water—insoluble
`excipients. significantly altered the lag time and the rel