`
`Filed on behalf of: KVK-Tech, Inc.
`
`By:
`
`Jonathan A. Harris (jharris@axinn.com)
`James T. Evans (jevans@axinn.com)
`Axinn, Veltrop & Harkrider LLP
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________
`
`KVK-Tech, Inc.
`Petitioner
`
`v.
`
`Shire PLC
`Patent Owner
`
`____________________
`
`U.S. Patent No. 8,846,100
`____________________
`
`DECLARATION OF DIANE J. BURGESS, PH.D.
`
`
`
`
`KVK-TECH EXHIBIT 1004
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`TABLE OF CONTENTS
`Overview .......................................................................................................... 1 
`  My Background and Qualifications ................................................................. 3 
`  List of Documents Considered in Formulating My Opinion .......................... 6 
`  POSA ............................................................................................................... 6 
`State of the Art before May 12, 2006 .............................................................. 7 
`  Modified Release Dosage Forms Were Well-Known before
`May 12, 2006 ......................................................................................... 7 
`Using Enteric Release Coatings to Delay Release of an Active
`Pharmaceutical Ingredient Was Well-Known before May 12,
`2006 ....................................................................................................... 9 
`Adderall IR® and Adderall XR® Were Well-Known ADHD
`Treatments before May 12, 2006 ........................................................ 10 
`  Amphetamine Formulations with Sustained Release Beads
`Were Well-Known before May 12, 2006 ............................................ 12 
`  The ‘100 Patent and Its Claims ...................................................................... 15 
`Independent Claim 1 ........................................................................... 18 
`Dependent Claims 2-31 ....................................................................... 19 
`Claim Construction ............................................................................. 20 
`“About” (claims 5-12 and 22-30) ............................................. 20 
`“Food effect” (claim 21) ........................................................... 21 
`  The Basis of My Analysis with Respect to Anticipation .............................. 21 
`The ‘300 Patent Discloses All the Elements of Claims 1-21
`and 31, Arranged as Claimed and in a Manner Enabling to a
`POSA ................................................................................................... 23 
`Claim 1 ...................................................................................... 23 
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`Claims 2-4 ................................................................................. 35 
`Claims 5-12 ............................................................................... 38 
`Claims 13-18 and 31 ................................................................. 40 
`Claims 19 and 20....................................................................... 44 
`Claim 21 .................................................................................... 46 
`  The Basis of My Analysis with Respect to Obviousness .............................. 48 
`Claims 1-31 Are Obvious to a POSA Reading the ‘300 Patent
`Alone or Adderall XR® in Combination with the ‘300 Patent ............ 50 
`The ‘300 Patent Alone (Petition Ground 2) Teachings
`and Rationales ........................................................................... 52 
`Independent claim 1 ........................................................ 52 
`Claims 2-4, 13-20 and 31 .............................................. 54 
`Claims 5-12 and 21 ......................................................... 57 
`Claims 22-30 ................................................................... 58 
`Reasonable Expectation of Success ................................ 59 
`Adderall XR® plus the ‘300 Patent (Petition Ground 3)
`Teachings and Rationales ......................................................... 60 
`Independent Claim 1 ....................................................... 60 
`Claims 2-4 ....................................................................... 67 
`Claims 5-12 ..................................................................... 69 
`Claims 13-18 and 31 ....................................................... 69 
`Claims 19 and 20 ............................................................ 72 
`Claim 21 .......................................................................... 73 
`Claim 22-30 .................................................................... 74 
`  Motivation to Combine ............................................................. 74 
`Reasonable Expectation of Success .......................................... 80 
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`Objective Indicia ................................................................................. 81 
`No Unexpectedly Superior Results ........................................... 82 
`Any Alleged Commercial Success Resulting from the
`‘100 Patent Has No Nexus to the Claims ................................. 84 
`  Conclusion ..................................................................................................... 84 
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`I, Diane J. Burgess, do hereby declare as follows:
`
`
`
`1.
`
`Overview
`I am over the age of 18 and otherwise competent to make this
`
`declaration. This declaration is based on my personal knowledge as an expert in
`
`pharmaceutical formulation. I understand this declaration is being submitted
`
`together with a petition for Inter Partes Review (“IPR”) of claims 1-31 of U.S.
`
`Patent No. 8,846,100 (the “‘100 patent”).
`
`2.
`
`I have been retained as an expert on behalf of KVK-Tech, Inc.
`
`(“KVK”), the Petitioner, for this IPR. I am being compensated for my time in
`
`connection with this IPR at my standard legal consultant rate. I have no personal or
`
`financial interest in KVK or in the outcome of this proceeding.
`
`3.
`
`I understand that the ‘100 patent issued on September 30, 2014, and
`
`resulted from U.S. Application No. 11/383,066, filed on May 12, 2006. I
`
`understand that, based on that date, the earliest possible filing date of the ‘100
`
`patent is May 12, 2006. I have been asked to provide my analysis of the ‘100
`
`patent based on prior art and the knowledge in the art before May 12, 2006.1 I also
`
`understand that the patent is assigned to Shire LLC (“Shire”) on its face.
`
`
`1 My opinions would not be affected should Shire establish an earlier invention date
`
`in 2005 or 2006.
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`
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`1
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`4.
`
`In preparing this declaration, I have reviewed the ‘100 patent
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`(EX1001) and considered each of the documents listed in Appendix I in light of the
`
`general knowledge in the art before May 12, 2006. I have also relied upon my
`
`experience in the relevant art and considered the viewpoint of a person of ordinary
`
`skill in the art (“POSA”; defined in § IV) before May 12, 2006.
`
`5.
`
`Claim 1, the sole independent claim, of the ‘100 patent is generally
`
`directed to a pharmaceutical composition comprising: (a) an immediate release
`
`bead comprising at least one amphetamine salt; (b) a first delayed release bead
`
`comprising at least one amphetamine salt; and (c) a second delayed release bead
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`comprising at least one amphetamine salt, wherein the first delayed release bead
`
`and the second delayed release bead provide different release profiles for the at
`
`least one amphetamine salt.
`
`6.
`
`Broadly, this declaration sets forth my opinion that claims 1-21 and 31
`
`of the ‘100 patent are anticipated by U.S. Patent No. 6,605,300 (the “‘300 patent”;
`
`EX1002) and that all claims of the ‘100 patent would have been obvious based on
`
`the prior art.
`
`7.
`
`First, it is my opinion that the ‘300 patent discloses all the elements of
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`claims 1-21 and 31 of the ‘100 patent, arranged as claimed and in a manner
`
`enabling to a POSA.
`
`8.
`
`Second, it is my opinion that claims 19, 20, and 22-30 of the ‘100
`
`
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`2
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`
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`patent are obvious based on the ‘300 patent along with a POSA’s knowledge of the
`
`state of the prior art, as discussed in this declaration below.
`
`9.
`
`Third, it is my opinion that a POSA would understand that claims 1-
`
`31 of the ‘100 patent are obvious based on the ‘300 patent alone or Adderall XR®
`
`(EX1003 or EX1031) in view of the ‘300 patent and a POSA’s knowledge of the
`
`state of the prior art, as discussed in this declaration below.
`
` My Background and Qualifications
`10. My qualifications and credentials are fully set forth in my curriculum
`
`vitae, attached as Appendix II. I am an expert in the field of pharmaceutical
`
`formulation. Over the past 37 years, I have accumulated significant training and
`
`experience in this field.
`
`11.
`
`I obtained my B.Sc. degree in Pharmacy from the University of
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`Strathclyde, Glasgow, U.K., in 1979. I was registered as a pharmacist
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`(M.R.Pharm.S.) in the U.K. in 1980. I received my Ph.D. in pharmaceutics from
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`the University of London, U.K., in 1984. I completed postdoctoral training in
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`pharmaceutical sciences at the University of Nottingham, U.K., in 1985, and the
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`University of North Carolina, in 1986.
`
`12.
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`I was Assistant and Associate Professor in Pharmaceutics at the
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`University of Illinois in Chicago from 1986 to 1992. I joined the faculty at the
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`University of Connecticut in 1993 as Associate Professor of Pharmaceutics and
`
`
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`3
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`was promoted to Full Professor of Pharmaceutics in 1999 and I am currently
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`Distinguished Professor of Pharmaceutics (appointed in 2009). I have taught
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`courses in controlled drug delivery, foundations of pharmaceutics, drug discovery
`
`and development, advanced biopharmaceutics, as well as interfacial and colloid
`
`chemistry.
`
`13.
`
`I was a Visiting Professor of the Office of Testing and Research at
`
`CDER at the U.S. Food and Drug Administration (“FDA”) in 2001 where I was
`
`working on performance testing of pharmaceutical dosage forms, including tablets.
`
`14.
`
`I have served on several professional organizations in the field of
`
`pharmaceutics and drug development. For example, I was the 2002 President of the
`
`American Association of Pharmaceutical Scientists (AAPS). AAPS is the largest
`
`professional organization globally representing scientists in Pharmaceutics,
`
`Biopharmaceutics, Drug Development, and related disciplines. I was the 2010
`
`President of the Controlled Release Society (CRS). This is an international
`
`professional organization focused on controlled release technologies for various
`
`actives including drugs and other bioactives.
`
`15.
`
`I am Editor of the International Journal of Pharmaceutics (2009 to
`
`date). From 2003 to 2012, I was Editor of the Journal of Drug Delivery Science
`
`and Technology. From 1999 to 2004, I was Editor of the American Association of
`
`Pharmaceutical Sciences Journal (AAPSJ). I currently serve on the Editorial
`
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`Advisory Board of 13 international journals relating to pharmaceutics,
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`biopharmaceutics, and related disciplines. I also serve as a referee for
`
`approximately 20 journals, including, for example, the Journal of Controlled
`
`Release, Critical Reviews in Therapeutic Drug Carrier Systems, Pharmaceutical
`
`Research, and Nature.
`
`16.
`
`I currently supervise a research group of 13 individuals including
`
`technicians, post-graduates, post-doctoral fellows, and a research assistant
`
`professor. I am/have been a major advisor to 35 Ph.D. and 5 M.S. students. In
`
`addition, I am/have been a major advisor to 18 postdoctoral fellows and 7 visiting
`
`research fellows. In addition, I am/have been a major advisor to 150 undergraduate
`
`research students. Since 1986, my research group has investigated controlled
`
`release formulations and their performance testing (including in vitro dissolution
`
`testing as well as in vivo pharmacokinetic and pharmacodynamics studies).
`
`17.
`
`I have authored or co-authored 206 peer reviewed publications. I have
`
`also authored two pharmaceutical books relating to drug delivery and drug release.
`
`I have authored 35 book chapters relating to drug delivery and drug release. In
`
`addition, I have made over 561 research presentations at major scientific meetings,
`
`including 278 invited lectures and presentations, and 21 keynote and plenary
`
`addresses, mostly relating to drug delivery and drug release.
`
`18.
`
`I have received various honors and awards throughout my career. For
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`example, I was the recipient of the 2014 AAPS Research Achievement Award in
`
`Formulation Design and Development, the 2014 AAPS Outstanding Educator
`
`Award, the 2014 CRS Distinguished Service Award, the 2013 AAPS IPEC Ralph
`
`Shangraw Memorial Award, the 2011 APSTJ Nagai International Women Scientist
`
`Award from the Japanese Pharmaceutical Science Association, the 2010 CRSI
`
`Fellowship for Outstanding Contributions in the Area of Drug Delivery, the 2007
`
`Outstanding Manuscript Award from the AAPS Journal, and the 2005 Pharmacy
`
`School Teacher of the Year Award.
`
`19. Accordingly, I am expert in the field of pharmaceutical formulation,
`
`and have been since 1984. For that reason, I am qualified to provide an opinion as
`
`to what a POSA would have understood, known, or concluded as of May 12, 2006.
`
` List of Documents Considered in Formulating My Opinion
`20.
`In formulating my opinion, I have considered all documents cited
`
`herein, including those listed in the Appendix I.
`
` POSA
`21.
`I understand that a POSA is a hypothetical person who is presumed to
`
`be aware of all the pertinent art, thinks along conventional wisdom in the art, and is
`
`a person of ordinary creativity. A POSA may work as a part of a multi-disciplinary
`
`team and draw upon not only his or her own skill, but also take advantage of
`
`certain specialized skills of others in the team, to solve a given problem. In regard
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`
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`to the ‘100 patent, a POSA typically would have had at least a Bachelor of Science
`
`Degree in Pharmacy, Chemistry, or Chemical Engineering, or similar field, and
`
`would have had experience in the field of pharmaceutics (including pharmaceutical
`
`formulation or pharmacokinetics or a similar technical field of study). A POSA
`
`would also have had access to and may have consulted with a pharmacologist with
`
`experience in the field of pharmacokinetics and/or an M.D. with clinical
`
`experience with ADHD and pharmacological treatments for ADHD.
`
`
`State of the Art before May 12, 2006
`22. Before May 12, 2006, the state of the art included the teachings
`
`provided by the references discussed in this Declaration. Additionally, a POSA,
`
`based on then-existing literature, would also have had general knowledge of
`
`pharmaceutical formulation and pharmacokinetics.
`
` Modified Release Dosage Forms
`Were Well-Known before May 12, 2006
`23. Controlled release drug delivery systems for oral use include those
`
`designed to delay release of the drug, release the drug over an extended period of
`
`time, and/or deliver the drug to a localized treatment area. (EX1023 at 27.) The
`
`goal of modified release dosage forms is thus to control the time, location, and/or
`
`rate of release of the drug within the body. (EX1027 at 14, 17.)
`
`24. Formulators generally design modified release dosage forms when an
`
`immediate release dosage form is not adequate for a given therapeutic goal. (Id. at
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`14-15.) For example, a formulator might be asked to design an extended release
`
`dosage form when the goal is to avoid the need to administer multiple daily doses
`
`of the drug, or to achieve specific blood levels of the drug over a certain period
`
`following administration. (Id.)
`
`25. A POSA can achieve control of the time, location, and/or rate of
`
`release of the drug within the body by using excipients that degrade at particular
`
`rates or in response to certain external conditions, such as pH. (Id. at 8-9.) To this
`
`end, the art described using coatings to modify release of pharmaceutical products
`
`to control one or more of the above aspects of drug release. (Id.) Specifically, the
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`active ingredient may be formulated into a core particle, to which a modified
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`release coating may be applied. (Id. at 8.)
`
`26. For example, for propranolol HCl the prior art taught a once daily
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`dosage form comprising (i) immediate release beads, (ii) delayed release beads
`
`with pH-dependent enteric coatings, and (iii) sustained release beads with pH-
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`independent coatings:
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`A therapeutic preparation consisting of three groups of spheroids
`containing an active medicinal substance. The first group of spheroids
`is uncoated and rapidly disintegrates upon ingestion to release an initial
`dose of medicinal substance[s], a second group of spheroids is coated
`with a pH sensitive coat to provide a second dose, and a third group of
`spheroids is coated with a pH independent coat to provide a third dose.
`
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`(EX1015 at [57] (abstract), 2:4-8.) The prior art taught similar dosage forms for
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`other active drugs, including carbamazepine (EX1016) and certain antibiotics
`
`(EX1017).
`
` Using Enteric Release Coatings to Delay Release of an Active
`Pharmaceutical Ingredient Was Well-Known before May 12, 2006
`27. An enteric coating is a type of delayed release coating. Enteric coating
`
`agents such as EUDRAGIT® L 30-D-55 (for triggering delayed pulsed release),
`
`and SURELEASE® (for triggering sustained release of active pharmaceutical
`
`agents), are early delayed release coatings in the art. Indeed, pharmaceutical
`
`products have employed enteric coatings since at least the late 1800s. (EX1024 at
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`4.) In general, enteric coatings protect the active ingredients in the core until fluids
`
`in the small intestine begin to dissolve the coating, reach the core, and facilitate
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`disintegration.
`
`28. Enteric coatings, thus, delay releasing the drug until the drug has
`
`passed through the stomach and provide for the rapid release of drug in the
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`intestine. (Id.; see EX1028 at 9; see also EX1029 at 10.) A POSA would have
`
`known that there are many reasons for employing an enteric coating in controlled
`
`release dosage forms, including to provide a delayed action. (EX1025 at 2.)
`
`29. An enteric coated dosage form should “disintegrate and release its
`
`contained medication as rapidly as possible once the dosage form empties from the
`
`stomach into the intestines.” (EX1026 at 4.) As Agyilirah explains, “[t]he fact that
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`an enteric tablet has adequate protection against gastric acid does not guarantee
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`that the tablet will be an effective dosage form/drug delivery system, unless the
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`enteric coating quickly dissolves/disintegrates on leaving the stomach, when it
`
`contacts a new environment.” (EX1024 at 5.)
`
` Adderall IR® and Adderall XR® Were
`Well-Known ADHD Treatments before May 12, 2006
`30. The art reported using amphetamine salts to treat Attention Deficit
`
`Hyperactivity Disorder (“ADHD”) for approximately 80 years, by May 12, 2006.
`
`(See, e.g., EX1011 at 3; EX1012.)
`
`31. FDA approved Adderall IR® – a drug product containing the mixed
`
`amphetamine salts (“MAS”) of dextroamphetamine sulfate, dextroamphetamine
`
`saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate – on
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`February 13, 1996. (EX1008 at 2.) Adderall IR® contained these MAS in
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`immediate release form. (Id.)
`
`32. One drawback of Adderall IR®, however, was the need for multiple
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`doses throughout the day. (See, e.g., EX1002 at 3:13-28.) Therefore, Shire
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`developed Adderall XR®, a drug product comprising the same MAS as Adderall
`
`IR® within immediate release beads and delayed pulsed beads with an enteric
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`coating. (See, e.g., id.) FDA approved Adderall XR® on October 11, 2001.
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`(EX1013 at 1-4.)
`
`33. The Adderall XR® PDR®, 2004 (“Adderall XR® PDR”) indicated that
`
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`10
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`its amphetamine salts did not exhibit a “food effect,” stating “[f]ood does not affect
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`the extent of absorption of ADDERALL XR® . . . .” (EX1003 at 5; see also
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`EX1014 at 12 (“the extent of absorption of [Adderall XR®] was not significantly
`
`altered after administration of a high-fat meal, allowing patients the option of
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`taking the capsule with or without food.”).)
`
`34.
`
`I understand that the Adderall XR® PDR qualifies as prior art to the
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`‘100 patent claims because it was published in 2004, which is prior to the May 12,
`
`2006 filing date of the ‘100 patent.
`
`35.
`
`I also understand that the Adderall XR® Label, 2004 (“Adderall
`
`Label”), which provides the same information as in Adderall XR® PDR plus
`
`information concerning the linear pharmacokinetics of the amphetamine salts in
`
`adults, qualifies as prior art to the ‘100 patent claims because it was published on
`
`August 11, 2004, which is prior to the May 12, 2006 filing date of the ‘100 patent.
`
`36. The Adderall XR® PDR and the Adderall Label are alternatives
`
`supporting the teachings of Adderall XR®. I will cite to the Adderall XR® PDR in
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`this declaration although the disclosures upon which I rely are found in both
`
`documents.2
`
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`2 Figure 1 on page 7 of EX1003 is a blowout of Figure 1 on page 5 of the Adderall
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`XR® PDR and is not a part of the original document. It has been added here for the
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`37. The Adderall XR® PDR teaches a two-bead pharmaceutical
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`composition comprising MAS contained in immediate release beads and delayed
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`release enteric coated beads. (EX1003 at 4; see also EX1020 at 2 (stating that
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`“[t]he Adderall XR formulation consists of two types of pellets . . . : an IR pellet
`
`and a delayed-release (DR) pellet. . . . The mechanism of drug release from the DR
`
`(enteric-coated) pellets . . . .”)
`
`38. Furthermore, the Adderall XR® PDR teaches that the two types of
`
`beads in its composition provide “double-pulsed delivery” of the MAS. (EX1003
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`at 4.) The Adderall XR® PDR contains a plasma concentration graph comparing
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`Adderall IR® and Adderall XR® that confirms this characterization. (Id. at 5, 7.)
`
`39. Some patients taking Adderall XR®, however, still required additional
`
`treatment to further extend the daily therapeutic effect. (EX1001 at 3:26-45;
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`EX1012.) Therefore, clinicians would instruct these patients to take a once daily
`
`dose of Adderall XR®, augmented with a dose of Adderall IR® 8-10 hours after the
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`Adderall XR® dose. (Id.; see also EX1010 at 2 (stating “[g]ive . . . Adderall XR
`
`early and IR around 6 PM”).)
`
` Amphetamine Formulations with Sustained
`Release Beads Were Well-Known before May 12, 2006
`40. Prior to the filing of the ‘100 patent, the prior art disclosed a solution
`
`
`reader’s convenience.
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`to the Adderall XR®-Adderall IR® dosing regimen: sustained release systems
`
`providing a comparable effect to taking a once daily dose of Adderall XR® and a
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`dose of Adderall IR® later in the day.
`
`41. For instance, U.S. Patent No. 6,322,819 (the “‘819 patent”), which I
`
`understand is prior art because it was issued on November 27, 2001 prior to the
`
`2006 filing date for the ‘100 patent, teaches a multiple bead system comprising
`
`MAS. In fact, the ‘819 patent teaches that its “product can be composed of either
`
`one or a number of beads in a dosage form . . . .” (EX1019 at [57] (abstract).) The
`
`‘819 patent states “the present invention provides an oral multiple pulsed dose
`
`delivery system for amphetamine salts . . . .” (Id. at 3:18-20.)
`
`42. The ‘819 patent’s specification also provides four examples of beads
`
`that can be combined to provide the multiple pulsed dose delivery system. (Id. at
`
`10:7-11:67.) Example 1 teaches an immediate release bead comprising MAS
`
`layered onto a sugar sphere core. (Id. at 10:7-31.) Example 2 teaches a delayed
`
`release bead that provides pulsed release, with the bead comprising an enteric
`
`coating (i.e., EUDRAGIT® L 30D-55) layered onto the amphetamine core. (Id. at
`
`10:32-64.) Example 3 is a delayed release bead, but with a different enteric coating
`
`agent (i.e., EUDRAGIT® 4110D) compared to Example 2. (Id. at 10:65-11:30.)3
`
`
`3 I understand that the difference in MASL concentration between Example 1 and
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`13
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`And Example 4 teaches adding a pH-independent sustained release coating (i.e.,
`
`SURELEASE®) over the enteric coating of the beads of either Example 2 or
`
`Example 3. (Id. at 11:30-67.)
`
`43. Similarly, the ‘300 patent, which I understand claims priority to the
`
`‘819 patent and is therefore also prior art to the ‘100 patent, discloses the same
`
`beads disclosed in Examples 1-4 of the ‘819 patent. (EX1002 at 10:30-12:26.) The
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`‘300 patent also contains an additional Example 5 that teaches a non-limiting
`
`example of a “pulsatile delivery system . . . achieved by combining the immediate
`
`release pellets (Example 1) with delayed release pellets (Example 2 or Example
`
`3).” (Id. at 12:27-47.) So, the ‘300 patent’s Example 5 teaches that the beads of the
`
`‘300 patent’s experimental examples can be combined in various combinations to
`
`make a single pharmaceutical composition.
`
`44. Finally, U.S. Patent Application Publication No. US2004/0059002
`
`(“the ‘002 application”), which I understand is prior art because it was published
`
`on March 25, 2004, prior to the 2006 filing date for the ‘100 patent, also teaches
`
`sustained release beads with amphetamine salts.
`
`45. The ‘002 application incorporates by reference the ‘300 patent as WO
`
`
`Example 2 of the ‘300 patent was an error that was later corrected in the reissued
`
`patent. This correction does not affect my opinions in this Declaration.
`
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`14
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`
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`00/23055. (EX1023 at ¶5.) I understand that WO 00/23055 is the international
`
`application of the ‘300 patent and was published on April 27, 2000. (EX1002 at
`
`[87].) The ‘002 application teaches sustained release formulations with an
`
`immediate release component, either as a layer on the sustained release bead or as
`
`a separate bead, to mimic the Adderall XR® plasma concentration profile.
`
`(EX1023 at ¶¶1, 10, 18-20, claim 11.)
`
` The ‘100 Patent and Its Claims
`46.
`I have considered sections of the prosecution history, and the
`
`complete ‘100 patent in light of the general knowledge in the art as of May 12,
`
`2006.
`
`47. The prosecution history is replete with inaccurate statements made by
`
`the Applicants. For example, applicants initially argued that the ‘300 patent did not
`
`disclose sustained release beads (EX1005 at 535, 536.) This is not true. Example 4
`
`of the ‘300 patent discloses a layered bead coated with amphetamine salts,
`
`followed by an enteric coating and then SURELEASE®. As explained in ¶¶69 and
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`74-75 below, SURELEASE® was a well-known sustained release coating.
`
`48. Applicants also incorrectly asserted that the “second delayed release
`
`bead” of the ‘100 patent has an “atypical construction,” not taught in the ‘300
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`patent, and amended claim 1 to recite “wherein the second delayed release bead
`
`comprises at least one amphetamine salt layered onto or incorporated into a core; a
`
`
`
`15
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`

`

`
`
`delayed release coating layered onto the amphetamine core; and a sustained release
`
`coating layered onto the delayed release coating.” (EX1005 at 645–646.) Yet, the
`
`beads in Example 4 of the ‘300 patent are the exact same “atypical” configuration,
`
`i.e., at least one amphetamine salt layered onto or incorporated into a core; a
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`delayed release (either EUDRAGIT® L 30D-55 or Eudragit® 4110D, both enteric)
`
`coating layered onto the amphetamine core; and a sustained release
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`(SURELEASE®) coating layered onto the delayed release coating. (EX1002 at
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`11:59-12:26.) The applicants’ statement to the contrary during prosecution was
`
`false.
`
`49. The Examiner appears to have allowed the claims based on the
`
`applicants’ misrepresentations because in the Notice of Allowance, the Examiner
`
`allowed the claims with only the following amendment “wherein the sustained
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`release coating is pH-independent.” (EX1005 at 784-786, 785.) However, the
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`Examiner appears not to have appreciated that SURELEASE® is a sustained
`
`release pH independent coating and was already used to coat the enteric coated
`
`amphetamine beads in Example 4 of the ‘300 patent. In short, the composition of
`
`claim 1 of the ‘100 patent was inherent in the ‘300 patent and was also obvious
`
`over the ‘300 patent alone or Adderall XR® (based on either the Adderall XR®
`
`PDR or the Adderall Label) in combination with the ‘300 patent.
`
`50. The ‘100 patent specification generally describes:
`
`
`
`16
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`

`

`
`
`A multiple pulsed dose drug delivery system for pharmaceutically
`active amphetamine salts, comprising a pharmaceutically active
`amphetamine salt covered with an immediate-release coating and a
`pharmaceutically active amphetamine salt covered with an enteric
`coating wherein the immediate release coating and the enteric coating
`provide for multiple pulsed dose delivery of the pharmaceutically
`active amphetamine salt.
`
`(EX1001 at [57] (abstract).) In addition, the ‘100 patent states, “[t]he present
`
`invention provides a long-acting amphetamine pharmaceutical composition, which
`
`includes an immediate release component, a delayed pulsed release component and
`
`a sustained release component, to meet the therapeutic needs for ADHD patients
`
`with longer-day demands.” (Id. at 3:53-57.) The ‘100 patent states that it provides
`
`a “once-daily longer-day treatment of ADHD by providing an amphetamine
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`pharmaceutical composition that is bioequivalent to an equal dosage of
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`ADDERALL XR®4 followed by an IR amphetamine composition 8 hours later.”
`
`(Id. at 3:57-62.) As such, the ‘100 patent relates to a multiple dose composition
`
`comprising pharmaceutically active amphetamine salts for the treatment of
`
`
`4 The ’100 patent states that “ADDERALL® . . . includes a mixture of four
`
`amphetamine salts: dextroamphetamine sulfate, dextroamphetamine saccharate,
`
`amphetamine aspartate monohydrate and amphetamine sulfate.” (EX1001 at 3:6-
`
`10.)
`
`
`
`17
`
`

`

`
`
`Attention Deficit Hyperactivity Disorder (ADHD).
`
`51.
`
`I understand that in an IPR, patent claim terms are given their
`
`broadest reasonable interpretation (“BRI”) as understood by a POSA, in view of
`
`their specification. It is my opinion, after reading the ‘100 patent’s specification,
`
`that a POSA reading the ‘100 patent would have understood that all the terms of
`
`claims 1-31 should be given their ordinary and customary meaning, except as
`
`discussed below. It is also my understanding that a dependent claim contains all
`
`the limitations of the claim from which it depends.
`
`
`Independent Claim 1
`52. Claim 1 recites:
`
`A pharmaceutical composition comprising:
`
`(a) an immediate release bead comprising at least one amphetamine
`salt;
`
`(b) a first delayed release bead comprising at least one amphetamine
`salt; and
`
`(c) a second delayed release bead comprising at least one amphetamine
`salt;
`
`wherein the first delayed release bead provides pulsed release of the at
`least one amphetamine salt and the second delayed release bead
`provides sustained release of the at least one amphetamine salt;
`
`wherein the second delayed release bead comprises at least one
`
`
`
`18
`
`

`

`
`
`amphetamine salt layered onto or incorporated into a core; a delayed
`release coating layered onto the amphetamine core; and
`
`a sustained release coating layered onto the delayed release coating,
`wherein the sustained release coating is pH-independent; and
`
`wherein the first delayed release bead and the second delayed release
`bead comprise an enteric coating.
`
`(EX1001 at 31:59-32:37.) An illustration of the beads recited in claim 1 is
`
`produced below:
`
`
`
` Dependent Claims 2-31
`53. Claims 2-31 depend directly or indirectly from claim 1, and thus, I
`
`understand, contain each and every limitation of claim 1. Claims 2-4 further
`
`require that the enteric coating has certain aspects. Claims 5-12 further require that
`
`the pharmaceutical composition has certain pharmacokinetic parameters. Claims
`
`13-16 further require that the amphetamine core has certain characteristics. Claims
`
`17, 18 and 31 further require that the pharmaceutical comp