`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`
`AMNEAL PHARMACEUTICALS LLC and
`PAR PHARMACEUTICAL, INC.
`Petitioners
`
`v.
`
`JAZZ PHARMACEUTICALS, INC.
`Patent Owner
`
`_____________________
`
`CASE IPR: Unassigned
`_____________________
`
`DECLARATION OF ROBERT J. VALUCK, Ph.D., R.Ph.
`
`
`
`
`
`
`
`
`
`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`TABLE OF CONTENTS
`
`I. 
`
`Overview .......................................................................................................... 1 
`
`II.  My background and qualifications .................................................................. 7 
`
`III. 
`
`Person of ordinary skill in the art .................................................................. 11 
`
`IV.  State of the art ................................................................................................ 13 
`
`V. 
`
`The '107 patent and its claims ....................................................................... 17 
`
`A. 
`
`B. 
`
`C. 
`
`Claim 1 ................................................................................................ 18 
`
`Claim 4 ................................................................................................ 24 
`
`Orange Book listing of the '107 patent ................................................ 24 
`
`VI.  A POSA exercising reasonable diligence would have located the
`Advisory Committee Art ............................................................................... 25 
`
`VII.  Basis of my analysis with respect to obviousness ......................................... 26 
`
`A.  A POSA reading the ACA would have had a reason and the
`know-how to arrive at the methods of claims 1-6 ............................... 26 
`
`1. 
`
`Claim 1 ...................................................................................... 28 
`
`(a) 
`
`Preamble ......................................................................... 28 
`
`(b)  Claim 1, step 1.1 ............................................................. 32 
`
`(c)  Claim 1, step 1.2 ............................................................. 39 
`
`(d)  Claim 1, step 1.3 ............................................................. 45 
`
`(e)  Claim 1, step 1.4 ............................................................. 50 
`
`(f) 
`
`Claim 1, step 1.5 ............................................................. 56 
`
`2. 
`
`3. 
`
`4. 
`
`Claim 4 ...................................................................................... 77 
`
`Claims 2 and 5 ........................................................................... 78 
`
`Claims 3 and 6 ........................................................................... 90 
`
`ii
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`A POSA reading Talk About Sleep in view of Honigfeld and
`Elsayed, and further in view of Lilly would have had the reason
`and the know-how to arrive at the methods of claims 1-6 .................. 92 
`
`B. 
`
`1. 
`
`Claim 1 ...................................................................................... 93 
`
`(a) 
`
`Preamble ......................................................................... 93 
`
`(b)  Claim 1, step 1.1 ........................................................... 107 
`
`(c)  Claim 1, step 1.2 ........................................................... 128 
`
`(d)  Claim 1, step 1.3 ........................................................... 135 
`
`(e)  Claim 1, step 1.4 ........................................................... 136 
`
`(f) 
`
`Claim 1, step 1.5 ........................................................... 139 
`
`Claim 4 .................................................................................... 167 
`
`Claims 2 and 5 ......................................................................... 168 
`
`Claims 3 and 6 ......................................................................... 190 
`
`2. 
`
`3. 
`
`4. 
`
`VIII.  Secondary considerations of non-obviousness ............................................ 192 
`
`A.  No commercial success ..................................................................... 193 
`
`B. 
`
`C. 
`
`No long-felt but unmet need or failure of others............................... 194 
`
`No unexpected superior results ......................................................... 197 
`
`IX.  Conclusion ................................................................................................... 198 
`
`iii
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`I, Robert J. Valuck, do hereby declare as follows:
`
`I.
`
`Overview
`1.
`
`I am over the age of eighteen and otherwise competent to make this
`
`declaration. This declaration is based on my personal knowledge as an expert in
`
`the fields of drug safety, drug abuse prevention, and prescription drug distribution.
`
`I understand that this declaration is being submitted together with a petition for a
`
`Inter Partes Review ("IPR") of claims 1-6 of U.S. Patent No. 7,765,107 ("the
`
`'107 patent," AMN1001.)
`
`2.
`
`I have been retained as an expert witness on behalf of Amneal
`
`Pharmaceuticals LLC ("Amneal") and Par Pharmaceutical, Inc. ("Par") for this
`
`IPR. I am being compensated for my time in connection with this declaration at
`
`my standard consulting rate. I have no personal or financial interest in the outcome
`
`of this proceeding.
`
`3.
`
`I understand that the '107 patent issued on July 27, 2010, and resulted
`
`from U.S. Ser. No. 11/097,985, filed on April 1, 2005. I also understand that the
`
`U.S. Patent and Trademark Office ("USPTO") records state that the '107 patent is
`
`currently assigned to Jazz Pharmaceuticals, Inc. ("Jazz").
`
`4.
`
`The face page of the '107 patent lists other patent applications. I
`
`understand that the '107 patent is related to a patent application which was filed on
`
`December 17, 2002.
`
`
`
`
`1
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`In preparing this declaration, I have reviewed the '107 patent
`
`5.
`
`(AMN1001) and its file history (AMN1002). I have also considered each of the
`
`documents listed in the table below, in light of general knowledge in the art as of
`
`December 17, 2002.
`
`Amneal
`Exhibit #
`
`Description
`
`1003
`
`1004
`
`1005
`
`1006
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`FDA Peripheral & Central Nervous System Drugs Advisory
`Committee, Transcript and Slides ("Advisory Committee
`Transcript and Slides") (July 13, 2001)
`FDA Peripheral & Central Nervous System Drugs Advisory
`Committee, Briefing Information, Division of
`Neuropharmacological Drug Products Preliminary Clinical
`Safety Review of NDA 21-196 ("Preclinical Safety Review")
`(July 13, 2001)
`FDA Peripheral & Central Nervous System Drugs Advisory
`Committee, Briefing Information, Briefing Booklet ("Briefing
`Booklet") (July 13, 2001)
`FDA Peripheral & Central Nervous System Drugs Advisory
`Committee, Briefing Information, Xyrem Prescription and
`Distribution Process Video and Transcript ("Xyrem Video and
`Transcript") (July 13, 2001)
`Shulman, S., "The Broader Message of Accutane," Am. J. of
`Public Health, 79:1565-1568 (1989)
`Lilly et al., U.S. Patent Appl. Pub. No. 2004/0176985 (filed
`Mar. 18, 2004; published Sep. 9, 2004) ("Lilly")
`Honigfeld, G., "Effects of the Clozapine National Registry
`System on Incidence of Deaths Related to Agranulocytosis,"
`Psychiatric Services, 47:52-56 (1996)
`Burleson, K., "Review of computer applications in institutional
`pharmacy—1975-1981," Am. J. Hosp. Pharm., 39:53-70 (1982)
`Zeldis, J., et al., "S.T.E.P.S.™: A Comprehensive Program for
`Controlling and Monitoring Access to Thalidomide," Clin.
`Therapeutics, 21:319-330 (1999)
`2
`
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`
`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`Amneal
`Exhibit #
`
`Description
`
`1014
`
`1015
`
`1016
`
`1019
`
`1021
`
`1022
`
`1023
`
`1027
`
`1029
`
`1032
`
`"Managing the Risks from Medical Product Use: Creating a
`Risk Management Framework," Report to the FDA
`Commissioner from the Task Force on Risk Management, U.S.
`Dept. of Health and Human Services, Food and Drug
`Administration (1999)
`66 Fed. Reg. 24391
`File History for U.S. Patent No. 7,668,730 (filed Dec. 17, 2002;
`issued Feb. 23, 2010)
`Peripheral and Central Nervous System Drugs Advisory
`Committee, Briefing Information, from FDA Central Website
`(June 6, 2001)
`Orange Book Entries for Xyrem®, available at
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cf
`m?Appl_No=021196&TABLE1=OB_Rx; and
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.
`cfm?Appl_No=021196&Product_No=001&table1=OB_Rx
`Rome, E., "It's a rave new world: Rave culture and illicit drug
`use in the young," Cleveland Clinic J. of Med., 68:541-550
`(2001)
`FDA, Center for Drug Evaluation and Research, NDA 21-196,
`Approved Labeling, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-
`196_Xyrem_prntlbl_P1.pdf
`FDA's Center for Drug Evaluation and Research, Advisory
`Committees CDER 2001 Meeting Documents, available at
`http://www.fda.gov/ohrms/dockets/ac/cder01.htm#Peripheral%
`20&%20Central%20Nervous 1/
`Mitchell, A., "A Pregnancy-Prevention Program in Women of
`Childbearing Age Receiving Isotretinoin," The New England
`Journal of Medicine, 333:101-106 (1995)
` Scrima, L., et al., "Efficacy of Gamma-Hydroxybutyrate versus
`Placebo in Treating Narcolepsy-Cataplexy: Double-Blind
`Subjective Measures," Biol. Psych., 26:331-343 (1989).
`
`
`
`
`3
`
`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`Description
`
`Talk About Sleep, "An Interview with Orphan Medical about
`Xyrem®," available at http://www.talkaboutsleep.com/an-
`interview-with-orphan-medical-about-xyrem/ ("Talk About
`Sleep") (Feb. 12, 2001)
`Honigfeld, G., et al., "Reducing Clozapine-Related Morbidity
`and Mortality: 5 Years of Experience with the Clozaril National
`Registry," J. Clin. Psych. 59 (suppl. 3): 3-7 ("Honigfeld")
`(1998)
`Elsayed et al., U.S. Patent No. 6,045,501 (filed Aug. 28, 1998;
`issued Apr. 4, 2000) ("Elsayed")
`
`Amneal
`Exhibit #
`
`1033
`
`1034
`
`1035
`
`1036
`
`U.S. Provisional Appl. No. 60/332,807 (filed Nov. 14, 2001)
`
`6.
`
`Generally, the '107 patent claims are directed to a method of
`
`distributing a prescription drug using an exclusive central pharmacy that
`
`comprises: (1) controlling with a computer processor the distribution of said
`
`prescription drug via an exclusive central pharmacy that maintains a central
`
`database that tracks all prescriptions of said prescription drug and analyzes for
`
`potential abuse situations; (2) receiving in the computer processor all prescription
`
`requests, for any and all patients being prescribed the prescription drug, only at the
`
`exclusive central pharmacy, from any and all medical doctors allowed to prescribe
`
`the prescription drug; (3) processing with the computer processor all prescriptions
`
`for the prescription drug only by the exclusive central pharmacy using only the
`
`central database; (4) determining with the computer processor current and
`
`
`
`
`4
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`anticipated patterns of potential prescription abuse of said prescription drug from
`
`periodic reports generated only by the central database based on prescription
`
`request data from a particular medical doctor and further based on filling of
`
`prescriptions by a particular patient, wherein said request data contain information
`
`identifying the patient, the drug prescribed, and credentials of the medical doctor;
`
`(5) selecting with the computer processor multiple controls for distribution by said
`
`exclusive central pharmacy, the controls comprising communicating prescriptions
`
`from a physician to the central pharmacy; identifying the physician's name,
`
`license, and DEA (Drug Enforcement Agency) registration information; verifying
`
`the prescription; obtaining patient information; verifying the physician is eligible
`
`to prescribe the prescription drug by consulting the National Technical
`
`Information Services to determine whether the physician has an active DEA
`
`number and to check on whether any actions are pending against the physician;
`
`providing comprehensive printed materials to the physician; contacting the
`
`patient's insurance company if any; verifying patient registry information;
`
`providing comprehensive education information to the patient; verifying the
`
`patient has reviewed the educational materials; verifying the home address of the
`
`patient; shipping via US postal service or a commercial shipping service;
`
`receiving the name of an at least 18 year old designee to receive the drug;
`
`confirming receipt of an initial shipment of the drug to the patient returning the
`5
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`drug to the pharmacy after two attempts to deliver; launching an investigation
`
`when a shipment is lost; shipping to another pharmacy for delivery; requiring
`
`manufacture at a single location; releasing inventory in a controlled manner to the
`
`central pharmacy; questioning early refills; flagging repeat instances of lost,
`
`stolen, destroyed, or spilled prescriptions; limiting the prescription to a one month
`
`supply; requiring rewriting of the prescription periodically; and making the
`
`database available to the DEA for checking for abuse patterns in the data, for cash
`
`payments, and for inappropriate questions.
`
`7.
`
`It is my opinion that a person of ordinary skill in the art ("POSA")
`
`would have had a reason and the know-how to arrive at the subject matter recited
`
`in claims 1-6 of the '107 patent in view of the Advisory Committee Art
`
`(AMN1003-AMN1006) ("ACA"), as discussed in this declaration below, with a
`
`reasonable expectation of success.
`
`8.
`
`It is also my opinion that a POSA would have had a reason and the
`
`know-how to arrive at the subject matter recited in claims 1-6 of the '107 patent in
`
`view of Talk About Sleep (AMN1033), Honigfeld (AMN1034), Elsayed
`
`(AMN1035), and Lilly (AMN1010), as discussed in this declaration below, with a
`
`reasonable expectation of success.
`
`
`
`
`6
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`In formulating my opinions, I have relied upon my experience in the
`
`9.
`
`relevant art. I have also considered the viewpoint of a POSA (i.e., a person of
`
`ordinary skill as set forth below in ¶22) as of December 17, 2002.
`
`II. My background and qualifications
`10. My qualifications and credentials are fully set forth in my curriculum
`
`vitae, attached as AMN1008. I am an expert in the fields of drug safety, drug
`
`abuse prevention, and prescription drug distribution. I am knowledgeable about
`
`the methods used in the fields of drug safety, drug abuse prevention, and
`
`prescription drug distribution. I also have many years of experience with
`
`computerized control of the distribution of pharmaceutical products. I have been
`
`an expert in these fields since 1994. For the past 20 years, I have accumulated
`
`significant training and experience in these and related fields.
`
`11.
`
`I received a Bachelor's Degree in Pharmacy from the University of
`
`Colorado School of Pharmacy in Denver, Colorado in 1987. I received a Master's
`
`Degree in 1992 and a Ph.D. in 1994 in Pharmacy Administration from the
`
`University of Illinois at Chicago in Chicago, Illinois.
`
`12. Since 1987, I have been a registered pharmacist in the state of
`
`Colorado. And, since 1989, I have been a registered pharmacist in the state of
`
`Illinois.
`
`
`
`
`7
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`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`In 1987, I was a Pharmacist at Hodel's Drug in Denver, Colorado.
`
`13.
`
`From 1987 to 1988, I was a Pharmacy Manager at Watson's Tabor Center Drug in
`
`Denver, Colorado. In these positions, I was a practicing pharmacist (and, at the
`
`latter, manager of the pharmacy component of a full service drug store), and
`
`performed all usual and customary duties, including filling prescriptions, entering
`
`patient information into computer database systems, contacting physicians to
`
`verify prescriptions, submitting insurance claims for payment, maintaining
`
`product inventory, ordering products from wholesalers, running dispensing
`
`reports, maintaining controlled substance inventory records, and performing other
`
`duties as needed to operate the pharmacy.
`
`14. From 1988 to 1989, I was a Decentralized Pharmacist at University
`
`Hospital in Denver, Colorado. In this position, I performed all usual and
`
`customary duties of a hospital clinical pharmacist, including taking medication
`
`histories from patients, interacting and providing drug-related advice to physicians
`
`and nurses, filling prescriptions, entering patient information into computer
`
`database systems, running reports for specific patients and prescribers, counseling
`
`patients prior to hospital discharge, and performing other duties as needed to serve
`
`the patient population.
`
`15. From 1989 to 1993, I was a Registered Pharmacist at Pharmstaff, Inc.
`
`in Chicago, Illinois. In this position, I was a temporary ("relief") pharmacist, and
`8
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`

`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`worked shifts at various retail and hospital pharmacies in the Chicago area,
`
`performing all usual and customary duties in these settings. This included all
`
`duties listed in items 13 and 14 above—with use of a variety of computer systems
`
`(varying by location, but common in their purpose and uses).
`
`16. From 1990 to 1993, I was a Clinical Pharmacist at Critical Care
`
`America in Elk Grove, Illinois. From 1993 to 1994, I was a Clinical Pharmacist at
`
`Cardiac Alliance in Northbrook, Illinois. In this position, I performed all usual and
`
`customary duties of a home health care (aka "home infusion therapy") pharmacist
`
`serving a national market, including receiving and entering prescriptions into
`
`computer database systems, preparing custom infusion therapy products for
`
`patients, supervising secure shipping of products to patients across the United
`
`States, monitoring patients' therapeutic progress via remote telemetry systems,
`
`communicating with physicians and nurses regarding patient status, and running
`
`patient and provider specific reports regarding drug therapy.
`
`17. From 1994 to 2001, I was an Assistant Professor in the Department of
`
`Pharmacy Practice at the University of Colorado-Denver. From 1998 to 2003, I
`
`was a Guest Lecturer for the Primary Care Residency Program at the University of
`
`Colorado School of Medicine. From 2001 to 2008, I was an Associate Professor in
`
`the Department of Clinical Pharmacy at the University of Colorado-Denver.
`
`
`
`
`9
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`

`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`18. Since 1994, I have been a Graduate Faculty Member in the
`
`Department of Pharmaceutical Sciences at the University of Colorado-Denver.
`
`Since 1996, I have been a member of the Graduate College at the University of
`
`Colorado-Denver. Since 2006, I have been a Guest Lecturer in the Department of
`
`Preventive Medicine and Biometrics at the University of Colorado School of
`
`Medicine. Since 2008, I have been a Professor in the Department of Clinical
`
`Pharmacy at the University of Colorado-Denver School of Pharmacy. Since 2009,
`
`I have been a Professor in the Department of Family Medicine at the University of
`
`Colorado-Denver School of Medicine. Since 2011, I have been a Professor in the
`
`Department of Epidemiology at the Colorado School of Public Health.
`
`19. Since 1995, I have received over 53 grants and contracts to study
`
`prescription drug safety, abuse prevention, and distribution. I have published over
`
`80 papers in peer-reviewed journals on topics including prescription drug safety,
`
`abuse prevention, and distribution. I serve as a reviewer for professional journals
`
`in my field and am a member of the Editorial Boards of Advances in
`
`Pharmacoepidemiology and Current Medical Research and Opinion. Since 2002,
`
`I have been a member of the Risk Management and Medication Compliance
`
`Special Interest Groups of the International Society for Pharmacoeconomics and
`
`Outcomes Research. I am a member of multiple professional societies including
`
`the Academy of Managed Care Pharmacy, the American Association of Colleges
`10
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`of Pharmacy, the American Pharmacists Association, the Drug Information
`
`Association, the International Society for Pharmacoeconomics and Outcomes
`
`Research, and the International Society for Pharmacoepidemiology. I have
`
`collaborated with several prominent researchers in the fields of drug safety, drug
`
`abuse prevention, and prescription drug distribution. In addition to my educational
`
`training, professional experiences, and research experiences described above, I
`
`attend conferences on drug safety, drug abuse prevention, and prescription drug
`
`distribution each year, and I have been invited to speak at such conferences.
`
`20. Accordingly, I am an expert in the fields of drug safety, drug abuse
`
`prevention, and prescription drug distribution. I also have expertise in the practice,
`
`administration, and day-to-day operations of pharmacy, including computerized
`
`control of the distribution of pharmaceutical products. Additionally, I have
`
`experience dispensing drugs subject to risk management programs, such as
`
`Accutane® and Clozaril®. Moreover, I have experience in evaluating the risks
`
`associated with prescription drug use. I am qualified to provide an opinion as to
`
`what a POSA would have understood, known or concluded as of December of
`
`2002. Additionally, I at least meet the criteria of a POSA as outlined below.
`
`III. Person of ordinary skill in the art
`21.
`I understand that a POSA is a hypothetical person who is presumed to
`
`be aware of all pertinent art, thinks along conventional wisdom in the art, and is a
`
`
`
`
`11
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`person of ordinary creativity. A POSA may work as part of a multi-disciplinary
`
`team and draw upon not only his or her own skills, but also take advantage of
`
`certain specialized skills of others in the team, to solve a given problem. For
`
`example, a POSA would hold a Bachelor's or Doctor of Pharmacy degree and a
`
`license as a registered pharmacist with 3-5 years of relevant work experience, or a
`
`computer science undergraduate degree or equivalent work experience and work
`
`experience relating to business applications, for example, including familiarity
`
`with drug distribution procedures. Alternatively, a POSA may have a blend of
`
`computer science and pharmacy drug distribution knowledge and/or experience.
`
`For example, such a POSA may have computer science education qualifications
`
`and experience relating to computerized drug distribution systems, or pharmacy
`
`education qualifications and experience relating to computerized drug distribution
`
`systems. A POSA would have had knowledge of the literature concerning
`
`pharmacy practice and prescription drug distribution, such as the prior art
`
`presented herein, that was available before the earliest effective filing date of the
`
`'107 patent, including knowledge about methods employed in the art. Accordingly,
`
`a POSA would have been well aware of techniques related to the mitigation of the
`
`risk associated with the distribution of potentially hazardous, but therapeutically
`
`beneficial, prescription drugs.
`
`
`
`
`12
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`IV. State of the art
`22. The mitigation of the risks associated with the distribution of
`
`potentially hazardous prescription drugs was well-known in the art. For example,
`
`in 1982, Hoffman-La Roche ("Roche") gained approval for Accutane®
`
`(isotretinoin). (AMN1009, 1565:2, ¶1.) However, it soon became apparent that
`
`Accutane® was a potent teratogen that was responsible for several birth defects.
`
`(Id., 1565:1, ¶¶1, 3.) To address that risk, Roche developed a Pregnancy
`
`Prevention Program Kit for distribution to physicians who prescribe Accutane.
`
`(Id., 1567:1, ¶2.) The kit included various forms, such as an informed consent
`
`document, that the patient and doctor must fill out indicating that they understand
`
`the risks associated with using Accutane®. (Id., 1567:1, ¶¶1, 2.) The Accutane®
`
`mitigation plan also included patient counseling on the teratogenic risk of
`
`Accutane®, the need to avoid pregnancy, and the practicing of proper birth control
`
`methods. (Id.) Additionally, women of childbearing potential had to test serum
`
`negative for a pregnancy within two weeks prior to beginning treatment. (Id.)
`
`23. Following in the footsteps of Accutane®, in 1990, Clozaril®
`
`(clozapine) entered the United States market for the treatment of treatment-
`
`resistant schizophrenia. (AMN1011, 52:1, ¶1 and 53:2, ¶1.) However, Clozaril®
`
`use was associated with agranulocytosis, a potentially fatal blood disorder
`
`resulting in white blood cell loss. (Id., Abstract, 52:1, and 53:1, ¶1.) To mitigate
`13
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`the manufacturer
`
`the distribution of Clozaril®,
`
`these risks and control
`
`implemented a national registry system that limited the distribution of the drug.
`
`(Id., 52:2, ¶2.) The distribution system required registration in an integrated
`
`computerized database—collecting information identifying the patient and the
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`physician. (Id., 53:2, ¶3.) Additionally, each filling of the prescription required the
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`physician to measure the patient's white blood cell count—terminating treatment if
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`the patient tests positive for agranulocytosis. (Id., 53:1, ¶¶1, 2.) If a patient or
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`physician was non-compliant with the program, the national registry took
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`corrective action, such as contacting and re-educating the prescribing physician
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`and/or discontinuing supplying of the prescription to the patient. (Id., 53:1, ¶¶1
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`and 53:3, ¶3.) Overall, the Clozaril® distribution system resulted in 97%
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`patient/physician compliance over its first five years of implementation. (Id., 53:3,
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`¶2.)
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`24. And while the use of a computer differentiated the Clozaril® system
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`from the Accutane® system, the use of a computer was not novel to prescription
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`drug distribution, and especially distribution of hazardous drugs, because by 1990
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`pharmacies had long been using computers when filling prescriptions. (See, e.g.,
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`AMN1012, 53:1 and 56:2, ¶1 through 61:1, ¶3.)
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`25.
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`In 1999, on the heels of Accutane® and Clozapine® restricted
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`distribution systems, the manufacturers of prescription thalidomide—a known
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`teratogen—developed a hybrid system, taking the computerized registry system of
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`Clozaril® and the pregnancy monitoring, pregnancy prevention steps, and
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`informed consent requirements of Accutane®. (AMN1013, 319:1, ¶1, 320:2, ¶1,
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`324:1, ¶2, 325 (all) and 327:2, ¶¶3, 4.) Additionally, attempts at early re-fills were
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`blocked. (Id.) This computerized registry system and preventative testing served to
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`monitor and control the distribution of the drug. (Id., 328:2, ¶¶1, 2 and 329:2, ¶2.)
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`26. As such, by 1999, at least three systems for the distribution of
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`effective yet hazardous prescription drugs were known in the art and implemented
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`in the industry. Realizing the necessity of developing "[a] better understanding of
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`risks and a more integrated risk management system [to] enable more effective
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`risk interventions," the FDA convened a task force to develop a framework for
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`risk management of medical products. (AMN1014, 1:¶1, and 2: ¶1.) Part of the
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`task force's recommendation was to increase "postmarketing risk interventions for
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`products with special risks, such as restricted distribution of products or requiring
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`mandatory educational programs for healthcare professionals and patients." (Id.,
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`15: ¶3.) For example, the task force pointed to the restricted computer-based
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`distribution of thalidomide as an example of a successful risk management
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`program, and noted that restricted distribution can be favorable for certain drugs.
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`(Id., 83: ¶2.)
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`15
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`27. Moreover, while risk management programs were developing during
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`the 1980s through 1990s, pharmacies were also making use of computerized
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`systems to track and control the distribution of controlled substances, i.e., drugs
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`with potential for abuse. (AMN1012, 56:2, ¶1 through 57:1, ¶1.) Because of the
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`need
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`to reduce
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`time commitment
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`to dispensing,
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`improve accuracy and
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`accountability, and streamline record keeping, the distribution of controlled
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`substances veered toward automation via the implementation of computerized
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`systems of distribution. (Id.) Computerized systems were helpful in accelerating
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`the process of generating reports that notified pharmacists if patients were
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`receiving excessive supplies of controlled substances. (Id., 56:2, ¶¶2, 3.)
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`Distribution of controlled substances could be tied to information identifying the
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`patient, the prescribing doctor, the quantity of the drug dispensed, and hospital
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`inventory of a drug. (Id., 56:2, ¶3.) In addition, the systems could be queried to
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`provide data, such as prescriptions by doctor and patient. (Id.) Ultimately, these
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`systems allowed for detecting patterns of abuse. (Id., 56:2, ¶1 through 57:1, ¶1.)
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`28. Consequently, by December of 2002, multiple sources existed in the
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`art that would have led a POSA to develop centralized distribution systems to
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`minimize
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`the risks associated with
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`the distribution of hazardous, but
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`therapeutically beneficial, prescription drugs.
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`16
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`
`V. The '107 patent and its claims
`29.
`I understand that this declaration is being submitted together with a
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`petition for IPR review of claims 1-6 of the '107 patent.
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`30.
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`I have considered the disclosure of the '107 patent in light of the
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`general knowledge in the art as of the earliest possible priority date of the '107
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`patent, which I understand to be December 17, 2002.
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`31. The '107 patent specification is generally directed towards "[a] drug
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`distribution system and method utiliz[ing] a central pharmacy and database to
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`track all prescriptions for a sensitive drug." (AMN1001, Abstract.) According to
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`the '107 specification, multiple controls are imposed on the distribution of the
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`prescription drug. (Id., 1:56-58.) Physician and patient prescription patterns are
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`monitored for abuse using an exclusive central database. Physician eligibility to
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`prescribe the drug is verified using a database, including determining whether
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`disciplinary actions have been brought against the physician. (Id., 1:48-56.) Prior
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`to shipping the prescription drug, the central pharmacy confirms whether the
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`patient has been educated about the prescription, and only ships the prescription
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`drug when no abuse is found related to the patient and prescribing doctor. (Id.,
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`1:59-67.) The prescription drug is then shipped to the patient. (Id., 1:59-2:3.)
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`32.
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`I have been informed that claim terms are given their broadest
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`reasonable interpretation, as understood by a POSA, in view of their specification.
`
`
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`17
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`Inter Partes Review of USPN 7,765,107
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`After reading the '107 patent's specification, it is my opinion that a POSA reading
`
`the '107 patent would have understood that all the terms of claims 1-6 should be
`
`given their ordinary meaning except as discussed below. It is also my
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`understanding that a dependent claim contains all the limitations of the claim from
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`which it dep