UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`
`
`PAR PHARMACEUTICAL, INC., Petitioner
`
`v.
`
`JAZZ PHARMACEUTICALS, INC.
`Patent Owner
`
`_____________________
`
`CASE IPR: Unassigned
`Patent 8,457,988
`_____________________
`
`DECLARATION OF ROBERT J. VALUCK, Ph.D., R.Ph.
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`Inter Partes Review of USPN 8,457,988
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`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 ................................................................................................ 12
`
`V.
`
`The ’988 patent and its claims ....................................................................... 16
`
`A.
`
`B.
`
`C.
`
`Claim 1 ................................................................................................ 18
`
`Claim 9 ................................................................................................ 25
`
`Claims 2–8 and 10–15 ......................................................................... 25
`
`D. Orange Book listing of the ’988 patent ............................................... 27
`
`VI. A POSA exercising reasonable diligence would have located the
`Advisory Committee Art. .............................................................................. 28
`
`VII. Basis of my analysis with respect to obviousness. ........................................ 29
`
`A. A POSA Reading the Advisory Committee Art would have had a
`reason and the know-how to arrive at the methods of claims 1–
`15.1, 3-9, and 11-15. ........................................................................... 29
`
`1.
`
`Claim 1 ...................................................................................... 31
`
`(a)
`
`Preamble ......................................................................... 31
`
`(b) Claim 1, step 1.1 ............................................................. 39
`
`(c) Claim 1, step 1.2 ............................................................. 51
`
`(d) Claim 1, step 1.3 ............................................................. 62
`
`(e) Claim 1, step 1.4 ............................................................. 67
`
`(f)
`
`Claim 1, step 1.5 ............................................................. 70
`
`(g) Claim 1, step 1.6 ............................................................. 75
`ii
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`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`(h) Claim 1, step 1.7 ............................................................. 80
`
`(i)
`
`Claim 1, step 1.8 ............................................................. 83
`
`Claim 9 ...................................................................................... 88
`
`Claims 3 and 11 ......................................................................... 89
`
`Claims 4 and 12 ......................................................................... 91
`
`Claims 5 and 13 ......................................................................... 96
`
`Claims 6, 7, and 14 ................................................................... 98
`
`Claims 8 and 15 .......................................................................100
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`B.
`
`A POSA reading Talk About Sleep in view of Honigfeld and
`Elsayed, and in further view of Lilly, would have had a reason
`and the know-how to arrive at the methods of claims 1–15. ............ 100
`
`1.
`
`Claim 1 ....................................................................................101
`
`(a)
`
`Preamble ....................................................................... 101
`
`(b) Claim 1, Step 1.1 .......................................................... 103
`
`(c) Claim 1, steps 1.2 and 1.3 ............................................. 111
`
`(d) Claim 1, step 1.4 ........................................................... 121
`
`(e) Claim 1, steps 1.5 and 1.6 ............................................. 125
`
`(f)
`
`Claim 1, step 1.7 ........................................................... 134
`
`(g) Claim 1, step 1.8 ........................................................... 135
`
`2.
`
`3.
`
`4.
`
`5.
`
`Claim 9 ....................................................................................142
`
`Claims 2 and 10 .......................................................................143
`
`Claims 3 and 11 .......................................................................146
`
`Claims 4 and 12 .......................................................................147
`
`
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`Claims 5 and 13 .......................................................................148
`
`Claims 6, 7, and 14 .................................................................153
`
`Claims 8 and 15 .......................................................................154
`
`6.
`
`7.
`
`8.
`
`C.
`
`D.
`
`E.
`
`Claims 2 and 10 would have been obvious over the Advisory
`Committee Art in view of Elsayed. ................................................... 154
`
`Claims 2 and 10 would have been obvious over the Advisory
`Committee Art in view of Korfhage. ................................................ 159
`
`Claims 2 and 10 would have been obvious over the Advisory
`Committee Art in view of Korfhage. ................................................ 161
`
`VIII. Secondary considerations of non-obviousness ............................................ 162
`
`A. No commercial success ..................................................................... 163
`
`B.
`
`C.
`
`No long-felt but unmet need or failure of others............................... 164
`
`No unexpected superior results ......................................................... 167
`
`IX. Conclusion ................................................................................................... 168
`
`
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`iv
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`Inter Partes Review of USPN 8,457,988
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`
`I, Robert J. Valuck, do hereby declare as follows:
`
`I.
`
`Overview
`1.
`
`I am over the age of eighteen (18) 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
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`petition for Inter Partes Review (“IPR”) of claims 1-15 of U.S. Patent No.
`
`8,457,988 (“the ’988 patent,” PAR1001.)
`
`2.
`
`I have been retained as an expert witness on behalf of Par
`
`Pharmaceutical, Inc. (“Par”). 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 ’988 patent issued on June 4, 2013, and resulted
`
`from U.S. Ser. No. 13/595,757, filed on August 27, 2012. I also understand that
`
`the U.S. Patent and Trademark Office (“USPTO”) records state that the ’988
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`patent is currently assigned to Jazz Pharmaceuticals, Inc. (“Jazz”).
`
`4.
`
`The face page of the ’988 patent lists another patent application. I
`
`understand that the ’988 patent is related to this patent application, which was
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`filed on December 17, 2002.
`
`
`
`1
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`Inter Partes Review of USPN 8,457,988
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`In preparing this declaration, I have reviewed the ’988 patent
`
`5.
`
`(PAR1001) and its file history (PAR1002). 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.
`
`Par
`Exhibit #
`
`Description
`
`1003
`
`1004
`
`1005
`
`1006
`
`1009
`
`1010
`
`1011
`
`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 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)
`
`Spurgeon D., “Advent of Mail-Order Pharmacy Causes Concern
`Among Some Pharmacists,” Can. Med. Assoc. J., 152:1485-
`1486 (1995)
`
`Honigfeld, G., “Effects of the Clozapine National Registry
`System on Incidence of Deaths Related to Agranulocytosis,”
`Psychiatric Services, 47:52-56 (1996)
`
`
`
`2
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`Par
`Exhibit #
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`1012
`
`1013
`
`1014
`
`Inter Partes Review of USPN 8,457,988
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
`
`
`Description
`
`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)
`
`“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)
`
`1015
`
`66 Fed. Reg. 24391
`
`1016
`
`File History for U.S. Patent No. 7,668,730 (filed Dec. 17, 2002;
`issued Feb. 23, 2010)
`
`1021
`
`1022
`
`1023
`
`1029
`
`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
`
`Mitchell, A., “A Pregnancy-Prevention Program in Women of
`Childbearing Age Receiving Isotretinoin,” The New England
`Journal of Medicine, 333:101-106 (1995)
`
`
`
`3
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`Inter Partes Review of USPN 8,457,988
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`
`Par
`Exhibit #
`
`Description
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`Scrima, L., et al., “Efficacy of Gamma-Hydroxybutyrate versus
`Placebo in Treating Narcolepsy-Cataplexy: Double-Blind
`Subjective Measures,” Biol. Psychiatry, 26:331-343 (1989).
`
`Talk About Sleep, “An Interview with Orphan Medical,”
`available at http://www.talkaboutsleep.com/an-interview-with-
`orphan-medical-about-xyrem/ (last visited Dec. 15, 2014)
`(“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,” Journal of Clinical Psychiatry 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”)
`
`Lilly et al., U.S. Patent Application No. 2004/0176985 A1 (filed
`Mar. 18, 2004 and claiming priority to U.S. Patent Application
`No. 10/062,251, filed Jan. 31, 2002; published Sep. 9, 2004)
`(“Lilly”)
`
`Korfhage, R.R., “Information Storage and Retrieval,” (1997)
`
`U.S. Provisional Patent Application Ser. No. 60/332,807 (“’807
`application) filed November 14, 2001.
`
`6.
`
`Generally, the ’988 patent claims are directed to methods of treatment
`
`of a narcoleptic patient with a prescription drug while controlling potential misuse,
`
`abuse or diversion that comprises: (1) receiving in a computer processor all
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`prescription requests for any and all patients only at the exclusive central
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`pharmacy; (2) entering information from the prescription requests into an
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`
`
`4
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`exclusive computer database associated with the exclusive central pharmacy and
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`processing the prescription requests only by the exclusive central pharmacy using
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`only the exclusive computer database; (3) checking with a computer processor the
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`credentials of the prescribing doctor to determine his eligibility to prescribe the
`
`drug; (4) checking for patterns of abuse using the exclusive computer database; (5)
`
`mailing and/or sending, or otherwise providing, the prescription drug to the patient
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`only if no abuse is found by the patient and prescribing doctor; and (6) generating
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`periodic reports using the computer processor and exclusive computer database to
`
`evaluate potential diversion patterns.
`
`7.
`
`It is my opinion that a person of ordinary skill in the art (“POSA”)
`
`would have had both a reason and the know-how to arrive at the subject matter
`
`recited in claims 1, 3-9, and 11-15 of the ’988 patent in view of the Advisory
`
`Committee Art (PAR1003-PAR1006) (“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 1-15 of the ’988 patent
`
`in view of Talk About Sleep (PAR1033), Honigfeld (PAR1034), Elsayed
`
`(PAR1035), and Lilly (PAR1036), as discussed in this declaration below, with a
`
`reasonable expectation of success.
`
`
`
`5
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`It is also my opinion that a POSA would have had both a reason and
`
`9.
`
`the know-how to arrive at the subject matter recited in claims 2 and 10 of the ’988
`
`patent in view of the Advisory Committee Art (PAR1003-PAR1006) (“ACA”)
`
`and Elsayed (PAR1035) as discussed in this declaration below, with a reasonable
`
`expectation of success.
`
`10.
`
`It is also my opinion that a POSA would have had both a reason and
`
`the know-how to arrive at the subject matter recited in claims 2 and 10 of the ’988
`
`patent in view of the Advisory Committee Art (PAR1003-PAR1006) (“ACA”)
`
`and Korfhage (PAR1037) as discussed in this declaration below, with a reasonable
`
`expectation of success.
`
`11.
`
`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 2 and 10 of the ’988
`
`patent in view of Talk About Sleep (PAR1033), Honigfeld (PAR1034), Elsayed
`
`(PAR1035), Lilly (PAR1036), and Korfhage (PAR1037) as discussed in this
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`declaration below, with a reasonable expectation of success.
`
`12.
`
`In formulating my opinions, I have relied upon my experience in the
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`relevant art. I have also considered the viewpoint of a POSA (i.e., a person of
`
`ordinary skill in the fields of drug safety, drug abuse prevention, and prescription
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`drug distribution) as of December 17, 2002.
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`
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`6
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`Inter Partes Review of USPN 8,457,988
`Declaration of Robert J. Valuck, Ph.D., R.Ph. (Exhibit 1007)
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`II. My background and qualifications
`13. My qualifications and credentials are fully set forth in my curriculum
`
`vitae, attached as PAR1008. I am an expert in the fields of drug safety, drug abuse
`
`prevention, and prescription drug distribution. I am knowledgeable about the
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`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
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`experience in these (and related) fields.
`
`14.
`
`I received a Bachelor’s Degree in Pharmacy from the University of
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`Colorado School of Pharmacy in Denver, Colorado in 1987. I received a Master’s
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`Degree in 1992 and a Ph.D. in 1994 in Pharmacy Administration from the
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`University of Illinois at Chicago in Chicago, Illinois.
`
`15. Since 1987, I have been a registered pharmacist in the state of
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`Colorado. And since 1989, I have been a registered pharmacist in the state of
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`Illinois.
`
`16.
`
`In 1987, I was a Pharmacist at Hodel’s Drug in Denver, Colorado.
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`From 1987 to 1988, I was a Pharmacy Manager at Watson’s Tabor Center Drug in
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`Denver, Colorado. In these positions, I was a practicing pharmacist (and at the
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`latter, manager of the pharmacy component of a full service drug store), and
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`
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`7
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`performed all usual and customary duties, including filling prescriptions, entering
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`patient information into computer database systems, contacting physicians to
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`verify prescriptions, submitting insurance claims for payment, maintaining
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`product inventory, ordering products from wholesalers, running dispensing
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`reports, maintaining controlled substance inventory and records, and other duties
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`as needed to operate the pharmacy.
`
`17. 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
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`the patient population.
`
`18. 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
`
`worked shifts at various retail and hospital pharmacies in the Chicago area,
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`performing all usual and customary duties in these settings. This included all
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`duties listed in items 13 and 14 above—with use of a variety of computer systems
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`(varying by location, but common in their purpose and uses).
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`19. From 1990 to 1993, I was a Clinical Pharmacist at Critical Care
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`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
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`customary duties of a home health care (aka “home infusion therapy”) pharmacist
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`serving a national market, including receiving and entering prescriptions into
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`computer database systems, preparing custom infusion therapy products for
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`patients, supervising secure shipping of products to patients across the United
`
`States, monitoring patients’ therapeutic progress via remote telemetry systems,
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`communicating with physicians and nurses regarding patient status, and running
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`patient and provider specific reports regarding drug therapy.
`
`20. 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.
`
`21. 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
`9
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`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.
`
`22. Since 1995, I have received over 53 grants and contracts to study
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`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
`
`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
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`collaborated with several prominent researchers in the fields of drug safety, drug
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`abuse prevention, and prescription drug distribution. In addition to my educational
`10
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`training, professional experiences, and research experiences described above, I
`
`attend conferences on drug safety, drug abuse prevention, and prescription drug
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`distribution each year, and I have been invited to speak at such conferences.
`
`23. 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
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`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
`24.
`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
`
`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
`
`
`
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`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
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`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
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`education qualifications and experience relating to computerized drug distribution
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`systems. A POSA would have had knowledge of the literature concerning
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`pharmacy practice and prescription drug distribution, such as the prior art
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`presented herein, that was available before the earliest effective filing date of the
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`’988 patent,
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`including knowledge about methods employed
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`in
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`the art.
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`Accordingly, a POSA would have been well aware of techniques related to the
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`mitigation of the risk associated with the distribution of potentially hazardous but
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`therapeutically beneficial prescription drugs.
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`IV. State of the art
`25. The mitigation of the risks associated with the distribution of
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`potentially hazardous prescription drugs was well-known in the art. For example,
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`in 1982, Hoffman-La Roche (“Roche”) gained approval for Accutane®
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`(isotretinoin). (PAR1009, 1565:2, ¶1.) However, it soon became apparent that
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`Accutane® was a potent teratogen that was responsible for several birth defects.
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`(Id., 1565:1, ¶¶1, 3.) Under pressure to respond, Roche developed a Pregnancy
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`Prevention Program Kit for distribution to physicians who prescribe Accutane®.
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`(Id., 1567:1, ¶2.) The kit included various forms, such as an informed consent
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`document, that the patient and doctor must fill out indicating that they understand
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`the risks associated with using Accutane®. (Id., 1567: 1, ¶¶1, 2.) The Accutane®
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`mitigation plan also included patient counseling on the teratogenic risk of
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`Accutane®, the need to avoid pregnancy, and the practicing of proper birth control
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`methods. (Id.) Additionally, women of childbearing potential had to test serum
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`negative for a pregnancy within two weeks prior to the start of treatment. (Id.)
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`26. Following in the footsteps of Accutane®, in 1990 Clozaril®
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`(clozapine) entered the United States market for the treatment of treatment-
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`resistant schizophrenia. (PAR1011, 52:1, ¶1 and 53:2, ¶1.) However, Clozaril®
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`use was associated with agranulocytosis, a potentially fatal blood disorder
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`resulting in white blood cell loss. (Id., 52:1, Abstract, and 53:1, ¶1.) To mitigate
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`these risks and control
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`the distribution of Clozaril®,
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`the manufacturer
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`implemented a national registry system that limited the distribution of the drug.
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`(Id., 52:2, ¶2.) The distribution system required registration in an integrated
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`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 tested 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 and
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`3, ¶3.) Overall,
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`the Clozaril® distribution
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`system
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`resulted
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`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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`27. 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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`PAR1012, 53:1 and 56:2, ¶1 through 61:1, ¶3.)
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`28. Based on the experiences of patients and doctors with Accutane® and
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`Clozapine®, the manufacturers of prescription thalidomide—a known teratogen—
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`developed a hybrid system, taking the computerized registry system of Clozaril®
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`and the pregnancy monitoring, pregnancy prevention steps, and informed consent
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`requirements of Accutane®. (PAR1013, 319:1, ¶1, 320:2, ¶1, 324:1, ¶2, 325:1, ¶1-
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`2:¶3, and 327:2, ¶¶3, 4.) Additionally, attempts at early re-fills were blocked. (Id.)
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`This computerized registry system and preventative testing served to monitor and
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`control the distribution of the drug. (Id., 328:2, ¶¶1, 2 and 329:2, ¶2.)
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`29. 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. (PAR1014, 1:¶1, and 2: ¶1.) Part of the task
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`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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`30. 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. (PAR1012, 56:2, ¶1 through 57:1, ¶1.) Because of the
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`need to reduce the time commitment to dispensing, 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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`31. 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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`V. The ’988 patent and its claims
`32.
`I understand that this declaration is being submitted together with a
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`petition for inter partes review of claims 1-15 of the ’988 patent.
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