Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`
`In the United States Patent and Trademark Office
`________________________________________
`
`Before the Patent Trial and Appeal Board
`________________________________________
`
`AMERIGEN PHARMACEUTICALS LIMITED,
`
`Petitioner,
`
` v
`
`
`
`SHIRE LLC,
`
`Patent Owner.
`______________________
`
`U.S. Patent No. 8,846,100 to Shojaei et al.
`Appln. No. 11/383,066, filed May 12, 2006
`Issue Date: September 30, 2014
`
`Title: CONTROLLED DOSE DRUG DELIVERY SYSTEM
`
`______________________
`
`Inter Partes Review No. Unassigned
`______________________
`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`
`
`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`Amerigen Ex. 1018, p. 1
`
`

`
`
`
`I.
`
`TABLE OF CONTENTS
`
`SUMMARY OF EDUCATION, PROFESSIONAL EXPERIENCE,
`AND QUALIFICATIONS ............................................................................ 1
`
`II.
`
`LEGAL PRINCIPLES .................................................................................. 5
`
`A.
`
`B.
`
`C.
`
`Claim Construction................................................................................ 5
`
`Anticipation ........................................................................................... 5
`
`Obviousness ........................................................................................... 6
`
`III. THE ’100 PATENT ....................................................................................... 7
`
`A.
`
`B.
`
`C.
`
`Patent bibliography................................................................................ 7
`
`The scope of my report with respect to the ’100 patent. .....................14
`
`The art that applies to the ’100 patent is biopharmaceutics. ...............15
`
`D. Description of the art during the relevant timeframe. .........................17
`
`E.
`
`The disclosure of the ’100 patent. .......................................................18
`
`IV. THE STATE OF THE ART .......................................................................23
`
`A. Amphetamines and methylphenidate were the drugs used to treat
`ADHD..................................................................................................23
`
`B.
`
`C.
`
`D.
`
`Drug delivery systems are ways of controlling how a drug is
`released in the body. ............................................................................25
`
`The art of making repeat-action dosage forms to relieve a patient of
`the burden of taking multiple single-dosages in a day was decades
`old by 2006. .........................................................................................26
`
`There is a long history of therapeutic use of mixed amphetamines,
`much of it for the treatment of attention deficit hyperactivity
`disorder (ADHD). ................................................................................30
`
`– i –
`
`Amerigen Ex. 1018, p. 2
`
`

`
`
`
`E.
`
`The widespread use of exterior coatings on dosage forms in the
`1995-2005 time period. .......................................................................31
`
`1.
`
`2.
`
`The use of HPMC-based film coatings on the exterior was
`common from 1995 until the filing of the application that
`eventually became the ’100 patent. .......................................... 33
`
`The use of modified film coatings to provide delayed pulsed
`release was common for decades prior to the filing of the
`application that eventually became the ’100 patent. ............... 33
`
`V.
`
`THE RELEVANT PATENTS AND PRINTED PUBLICATIONS ........35
`
`A. U.S. Patent No. 6,322,819. ..................................................................35
`
`B.
`
`C.
`
`U.S. Patent No. 6,605,300. ..................................................................39
`
`Kratochvil. ...........................................................................................41
`
`D. Additional references demonstrate that amphetamines required
`dose-titration, which was well known by a person of ordinary skill. .43
`
`VI HOW A PERSON OF ORDINARY SKILL IN THE ART WOULD
`READ THE WORDING OF THE CLAIMS IN VIEW OF THE
`DISCLOSURE OF THE ’100 PATENT AND THE ASSERTED ART .44
`
`VII ONE OF ORDINARY SKILL IN THE ART WOULD
`UNDERSTAND THE ’819 PATENT TO DISCLOSE EACH AND
`EVERY ELEMENT OF THE ’100 PATENT. .........................................47
`
`A.
`
`The ’819 patent discloses each limitation of claim 1 of the ’100
`patent. ..................................................................................................47
`
`1.
`
`2.
`
`3.
`
`“(a) an immediate release bead comprising at least one
`amphetamine salt;” .................................................................. 48
`
`“(b) a first delayed release bead comprising at least one
`amphetamine salt; and” ........................................................... 50
`
`“(c) a second delayed release bead comprising at least one
`amphetamine salt;” .................................................................. 53
`
`– ii –
`
`Amerigen Ex. 1018, p. 3
`
`

`
`
`
`4.
`
`5.
`
`“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;” .................................................. 57
`
`“wherein the second delayed release bead comprises at least
`one 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;” ....................................... 64
`
`6.
`
`“and wherein the first delayed release bead and the second
`delayed release bead comprise an enteric coating.” ............... 65
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`G.
`
`The ’819 patent discloses a pharmaceutical composition consisting
`of three beads. ......................................................................................66
`
`The ’819 patent discloses the limitations of dependent
`claims 2-4. ...........................................................................................68
`
`The ’819 patent discloses the pharmacokinetic parameters claimed
`in dependent Claims 5-12. ...................................................................71
`
`The ’819 patent teaches every limitation of claims 13-21. .................77
`
`The ’819 patent discloses claims 22-30. .............................................82
`
`The ’819 patent discloses claim 31. ....................................................86
`
`VIII. ONE OF ORDINARY SKILL IN THE ART WOULD
`UNDERSTAND THAT ALL CLAIMS OF THE ’100 PATENT ARE
`OBVIOUS IN LIGHT OF THE ’300 PATENT, IN VIEW OF
`KRATOCHVIL............................................................................................88
`
`A. One skilled in the art would be motivated to combine Kratochvil
`with the ’300 patent. ............................................................................88
`
`B.
`
`The ’300 patent, in view of Kratochvil, discloses each limitation of
`claim 1 of the ’100 patent. ...................................................................92
`
`– iii –
`
`Amerigen Ex. 1018, p. 4
`
`

`
`
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`“(a) an immediate release bead comprising at least one
`amphetamine salt;” .................................................................. 93
`
`“(b) a first delayed release bead comprising at least one
`amphetamine salt; and” ........................................................... 95
`
`“(c) a second delayed release bead comprising at least one
`amphetamine salt;” .................................................................. 98
`
`“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;” ................................................ 103
`
`a.
`
`b.
`
`“(1) the first delayed release bead [that] provides
`pulsed release of the at least one amphetamine salt” ...103
`
`“(2) second delayed release bead [that] provides
`sustained release of the at least one amphetamine salt”104
`
`“wherein the second delayed release bead comprises at least
`one 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;” ..................................... 107
`
`6.
`
`and wherein the first delayed release bead and the second
`delayed release bead comprise an enteric coating. ............... 109
`
`C.
`
`D.
`
`E.
`
`The ’300 patent discloses the enteric limitations of dependent
`Claims 2-4. ........................................................................................111
`
`The ’300 patent, in view of Kratochvil, discloses the
`pharmacokinetic parameters claimed in dependent claims 5-12. .....114
`
`The ’300 patent teaches every limitation of claims 13-21 and claim
`31. ......................................................................................................121
`
`F.
`
`The ’300 patent discloses every limitation of claims 22-30. ............126
`
`– iv –
`
`Amerigen Ex. 1018, p. 5
`
`

`
`G.
`
`The ’300 patent, in view of Kratochvil, teaches claim 31. ...............130
`
`H. No secondary considerations suggest that the ’100 patent was
`nonobvious. .......................................................................................134
`
`
`
`
`
`
`
`– v –
`
`Amerigen Ex. 1018, p. 6
`
`

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

`
`
`
`EX.
`
`Ex. 1021
`
`1021
`
`EX.
`
`Ex. 1022
`
`1022
`
`“Adderall,” Drugs@FDA (http://www.accessdata.fda.gov/)
`“Adderall,” Drugs @FDA (http://www.accessdata.fda.gov/)
`
`“Adderall XR,” Drugs@FDA (http://www.accessdata.fda.gov/)
`“Adderall XR,” Drugs @FDA (http: //WWW. accessdata.fda.gov/)
`
`EX.
`
`1023
`
`Ex. 1023 U.S. Patent No. 6,913,768
`6,913,768
`
`U.S. Patent No.
`
`EX.
`
`1024
`
`Ex. 1024 U.S. Patent No. 2,738,303
`2,738,303
`
`U.S. Patent No.
`
`Ex. 1025 U.S. Patent No. 5,407,686
`5,407,686
`
`EX.
`
`1025
`
`U.S. Patent No.
`
`EX.
`
`Ex. 1026 U.S. Patent Application Publication No. 2004/0197405
`U.S. Patent Application Publication No. 2004/0197405
`
`1026
`
`EX.
`
`1027
`
`Ex. 1027 U.S. Patent No. 5,837,284
`5,837,284
`
`U.S. Patent No.
`
`Ex. 1028 U.S. Patent No. 8,906,413
`8,906,413
`
`EX.
`
`1028
`
`U.S. Patent No.
`
`Ex. 1029 U.S. Patent No. 6,555,136
`6,555,136
`
`EX.
`
`1029
`
`U.S. Patent No.
`
`Ex. 1030 U.S. Patent No. 5,326,570
`5,326,570
`
`EX.
`
`1030
`
`U.S. Patent No.
`
`Ex. 1031 U.S. Patent No. 8,313,776
`8,313,776
`
`EX.
`
`1031
`
`U.S. Patent No.
`
`Ex. 1032 U.S. Patent No. 4,728,512
`4,728,512
`
`EX.
`
`1032
`
`U.S. Patent No.
`
`Ex. 1033 U.S. Patent No. 4,794,001
`4,794,001
`
`EX.
`
`1033
`
`U.S. Patent No.
`
`Ex. 1034 U.S. Patent No. 4,904,476
`4,904,476
`
`EX.
`
`1034
`
`U.S. Patent No.
`
`EX.
`
`1035
`
`U.S. Patent No.
`
`EX.
`
`Ex. 1036
`
`1036
`
`Ex. 1035 U.S. Patent No. 5,474,786
`5,474,786
`SURELEASE® Product Brochure
`SURELEASE® Product Brochure
`Ex. 1037 U.S. Patent No. RE42,096
`RE42,096
`
`EX.
`
`1037
`
`U.S. Patent No.
`
`EX.
`
`1038
`
`EX.
`
`1039
`
`EX.
`
`1040
`
`The ’066 application, Patent Publication No. 2007/0264323
`Ex. 1038
`The ’066 application, Patent Publication No. 2007/0264323
`Ex. 1039 OPADRY® Manufacturer Poster
`OPADRY® Manufacturer Poster
`Ex. 1040 Orange Book: Approved Drug Products with Therapeutic
`Orange Book: Approved Drug Products with Therapeutic
`Equivalence Evaluations: Patent and Exclusivity for: N021303
`Equivalence Evaluations: Patent and Exclusivity for: N021303
`Ex. 1041 Adderall® XR Medication Guide
`Adderall® XR Medication Guide
`June 2005 Package Insert for Adderall® Immediate Release (“IR”)
`Ex. 1042
`June 2005 Package Insert for Adderall® Immediate Release (“IR”)
`
`EX.
`
`1041
`
`EX.
`
`1042
`
`—vii—
`
`– vii –
`
`Amerigen Ex. 1018, p. 8
`
`Amerigen Ex. 1018, p. 8
`
`

`
`
`
`Ex. 1043 May 2005 Package Insert for Adderall® Extended Release (“XR”)
`Ex. 1044 The Merck Index, (Susan Budavari, ed., 11th ed., 1996)
`
`Ex. 1045
`
`Susan B Clausen, Single- and multiple-dose pharmacokinetics of an
`oral mixed amphetamine salts extended-release formulation in adults,
`CNS SPECTRUMS vol. 10 (Dec. 2005)
`
`Ex. 1046. Ansel, Popovich & Allen, Pharmaceutical Dosage Forms and Drug
`Delivery Systems (6th ed., 1995)
`Ex. 1047 Adderall® Immediate Release (“IR”) Medication Guide
`Ex. 1048
`Simon J. Tulloch, et al., SLI381 (Adderall XR), a Two-Component,
`Extended-Release Formulation of Mixed Amphetamine Salts:
`Bioavailability of Three Test Formulations and Comparison of Fasted,
`Fed, and Sprinkled Administration, PHARMACOTHERAPY vol. 22
`(2002)
`
`Ex. 1049
`
`Ex. 1050
`
`Ex. 1051
`
`1974: Physicians’ Desk Reference (28th ed., 1974)
`1993 Physicians’ Desk Reference (47th ed., 1992)
`1995 Physicians’ Desk Reference (49th ed., 1994)
`
`Ex. 1052
`
`1997 Physicians’ Desk Reference (51st ed., 1997)
`
`
`
`Ex. 1053
`
`Patricia K. Sonsalia, Remington: The Science and Practice of
`Pharmacy (19th ed., 1995)
`
`Ex. 1054 Brian B. Hoffman & Robert J. Lefkowitz, Goodman & Gilman’s The
`Pharmacological Basis of Therapeutics (9th ed., 1996)
`
`
`Ex. 1055 Charles S. L. Chiao & Joseph R. Robinson, Remington: The Science
`and Practice of Pharmacy (19th ed., 1995)
`
`Stuart C. Porter, Remington: The Science and Practice of Pharmacy
`(19th ed., 1995)
`
`1995 United States Pharmacopeia and National Formulary, USP 23-
`NF (1994)
`
`Ex. 1056
`
`Ex. 1057
`
`
`
`– viii –
`
`Amerigen Ex. 1018, p. 9
`
`

`
`
`
`Ex. 1058 W. H. Hartung & J. C. Munch, Amino Alcohols, VI. The Preparation
`and Pharmacodynamic Activity of Four Isomeric
`Phenylpropylamines, 53 J. AM. CHEM. SOC. (1931)
`
`Ex. 1059 Handbook of Pharmaceutical Excipients (Ainley Wade & Paul J
`Weller, ed., 2d ed., 1994)
`
`Ex. 1060
`
`Ex. 1061
`
`James R. McCowan, Dispensing of Medication (Eric W. Martin ed.,
`7th ed., 1971)
`Edward Stempel, Dispensing of Medication, (Eric W. Martin ed., 7th
`ed., 1971)
`
`Ex. 1062 U.S. Patent No. 1,879,003
`
`Ex. 1063 U.S. Patent No. 1,921,424
`
`Ex. 1064 Charles W. Popper, M.D., The Story of Four Salts, JOURNAL OF CHILD
`AND ADOLESCENT PSYCHOPHARMACOLOGY vol. 4, n. 4 (1994)
`
`Ex. 1065 Approval Letter from Robert Temple, M.D., Director, Office of Drug
`Eval., to William A. Nuerge, Chief Oper. Officer, Richwood Pharm.
`Co., Inc. (Feb. 13, 1996) (on file at
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/11522S010_A
`dderall.pdf)
`
`Ex. 1066 Approval Letter from Russell Katz, M.D., Director, Div. of
`Neuropharm. Drug Products, Office of Drug Eval., to Tami Martin,
`Vice Pres. of Reg. Affairs, Shire Labs., Inc. (Oct. 11, 2001) (on file at
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21303_Add
`erall_Approv.pdf)
`
`Ex. 1067 April 21, 2003 Resp. to Office Action dated March 4, 2003, App. No.
`09/807,462
`
`– ix –
`
`Amerigen Ex. 1018, p. 10
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`Challenged Claims of U.S. Patent No. 8,846,100
`
`(formatted into elements as analyzed in the petition)
`
`1. 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
`
`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.
`
`2. The pharmaceutical composition of claim 1, wherein the enteric coating is
`
`pH dependent.
`
`– x –
`
`Amerigen Ex. 1018, p. 11
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`3. The pharmaceutical composition of claim 1, wherein the first delayed
`
`release bead and the second delayed release bead comprise different
`
`enteric coatings.
`
`4. The pharmaceutical composition of claim 1, wherein the first delayed
`
`release bead and the second delayed release bead comprise the same
`
`enteric coating.
`
`5. The pharmaceutical composition of claim 1, wherein administration of a
`
`37.5 mg dose of the pharmaceutical composition to a human patient
`
`results in a d-amphetamine Cmax of about 50 ng/ml.
`
`6. The pharmaceutical composition of claim 1, wherein the d-amphetamine
`
`area under the curve from time 0 to the last measured time (AUC0-last),
`
`after administration of a 37.5 mg dose of the pharmaceutical composition
`
`to a human patient is about 1058 nghr/ml.
`
`7. The pharmaceutical composition of claim 1, wherein the d-amphetamine
`
`area under the curve from time 0 to time infinity (AUCo-inf) after
`
`administration of a 37.5 mg dose of the pharmaceutical composition to a
`
`human patient is about 1085 nghr/ml.
`
`8. The pharmaceutical composition of claim 1, wherein the d-amphetamine
`
`Tmax is about 8.2 hours after administration of a 37.5 mg dose of the
`
`pharmaceutical composition to a human patient.
`
`– xi –
`
`Amerigen Ex. 1018, p. 12
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`9. The pharmaceutical composition of claim 1, wherein the 1-amphetamine
`
`Cmax, after administration of a 37.5 mg dose of the pharmaceutical
`
`composition to a human patient is about 15 ng/ml.
`
`10. The pharmaceutical composition of claim 1, wherein the l-amphetamine
`
`area under the curve from time 0 to the last measured time (AUC0-last)
`
`after administration of a 37.5 mg dose of the pharmaceutical composition
`
`to a human patient is about 354 nghr/ml.
`
`11. The pharmaceutical composition of claim 1, wherein the 1-amphetamine
`
`area under the curve from time 0 to time infinity (AUCo-inf) after
`
`administration of a 37.5 mg dose of the pharmaceutical composition to a
`
`human patient is about 373 nghr/ml.
`
`12. The pharmaceutical composition of claim 1, wherein the 1-amphetamine
`
`Tmax, is about 8.4 hours after administration of a 37.5 mg dose of the
`
`pharmaceutical composition to a human patient.
`
`13. The pharmaceutical composition of claim 1, wherein the immediate
`
`release bead and at least one delayed release bead are present on a single
`
`core.
`
`14. The pharmaceutical composition of claim 1, wherein the immediate
`
`release bead and at least one delayed release bead are present on different
`
`cores.
`
`– xii –
`
`Amerigen Ex. 1018, p. 13
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`15. The pharmaceutical composition of claim 1, wherein the at least one
`
`amphetamine salt is coated onto a core.
`
`16. The pharmaceutical composition of claim 1, wherein the at least one
`
`amphetamine salt is incorporated into a core.
`
`17. The pharmaceutical composition of claim 1, which further comprises a
`
`protective layer over at least one enteric coating.
`
`18. The pharmaceutical composition of claim 1, which further comprises a
`
`protective layer between the amphetamine salt and at least one enteric
`
`coating.
`
`19. The pharmaceutical composition of claim 1, wherein the at least one
`
`amphetamine salt is selected from the group consisting of
`
`dextroamphetamine sulfate, dextroamphetamine saccharate,
`
`amphetamine aspartate monohydrate, amphetamine sulfate, and mixtures
`
`thereof.
`
`20. The pharmaceutical composition of claim 19, wherein the at least one
`
`amphetamine salt is a mixture of dextroamphetamine sulfate,
`
`dextroamphetamine saccharate, amphetamine aspartate monohydrate, and
`
`amphetamine sulfate.
`
`21. The pharmaceutical composition of claim 1, wherein the composition
`
`does not exhibit a food effect.
`
`– xiii –
`
`Amerigen Ex. 1018, p. 14
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`22. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 12.5 mg.
`
`23. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 18.75 mg.
`
`24. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 25 mg.
`
`25. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 31.25 mg.
`
`26. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 37.5 mg.
`
`27. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 43.75 mg.
`
`28. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 50 mg.
`
`29. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 62.5 mg.
`
`30. The composition of claim 1, wherein the amount of at least one
`
`amphetamine salt is about 75 mg.
`
`– xiv –
`
`Amerigen Ex. 1018, p. 15
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`31. The pharmaceutical composition of claim 1, wherein a protective coating
`
`is layered between the delayed release coating and the sustained release
`
`coating.
`
`
`
`– xv –
`
`Amerigen Ex. 1018, p. 16
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`I, Edmund J. Elder, Jr., Ph.D., R. Ph., declare as follows:
`
`I submit this declaration as my testimony in this case, on behalf of Amerigen
`
`Pharmaceuticals, Ltd., regarding meaning of certain claim terms of United States
`
`Patent No. 8,846,100 (Ex. 1001) (“the ’100 patent”), and the validity of the claims
`
`of the ’100 patent in view of the prior art. The matters set forth in this declaration
`
`arise either from my personal knowledge or from the documents that I have
`
`reviewed and attached hereto, as should be apparent.
`
`I.
`
`SUMMARY OF EDUCATION, PROFESSIONAL EXPERIENCE,
`AND QUALIFICATIONS
`
`1.
`
`I am the Director of the Zeeh Pharmaceutical Experiment Station in
`
`the School of Pharmacy at the University of Wisconsin-Madison (“the Station”)
`
`and have been since 2007. I was associate director for a year starting in 2006. My
`
`business address is: Zeeh Pharmaceutical Experiment Station, School of Pharmacy,
`
`University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705.
`
`2.
`
`I obtained my Bachelor of Science degree in Pharmacy and Doctor of
`
`Philosophy (Ph.D.) degree in Pharmaceutical Sciences from the Medical
`
`University of South Carolina in 1985 and 1989, respectively. I have over 30 years
`
`of experience characterizing materials used in the preparation of pharmaceutical
`
`products, formulating pharmaceutical products, including controlled-release drug
`
`delivery systems, and testing these formulations.
`
`– 1 –
`
`Amerigen Ex. 1018, p. 17
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`3. My current responsibilities as Director of the Station include
`
`overseeing all aspects of our services, including providing pharmaceutical pre-
`
`formulation and formulation expertise to support pharmaceutical and
`
`biopharmaceutical development collaborations across the University of Wisconsin
`
`system campuses and for clients outside the University. The Station works for both
`
`academia and pharmaceutical industry clients in developing and characterizing
`
`drugs and pharmaceutical formulations and providing technical expertise regarding
`
`issues arising during pharmaceutical formulation development and manufacture. I
`
`actively participate in educational programs sponsored by the Station in
`
`collaboration with the Division of Pharmacy Professional Development, a
`
`department in the School of Pharmacy at the University of Wisconsin-Madison, in
`
`which I teach pharmaceutical industry scientists and others in related fields about
`
`the process and science of drug development. I also serve as a guest lecturer for the
`
`graduate students in the Pharmaceutical Sciences Division providing lectures on an
`
`overview of pharmaceutical development and an introduction to formulation
`
`development, with a focus on properties of materials. Additionally, I am the course
`
`co-coordinator and senior lecturer for the Biotechnology Operations course in the
`
`Master of Science in Biotechnology program in the School of Medicine and Public
`
`Health at the University of Wisconsin-Madison. I teach sessions that include an
`
`overview of biopharmaceutical development, regulatory operations, CMC
`
`– 2 –
`
`Amerigen Ex. 1018, p. 18
`
`

`
`(chemistry, manufacturing and controls) operations, pre-clinical operations, and
`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`clinical operations.
`
`4.
`
`I am currently a member of the 2015-2020 United States
`
`Pharmacopeia (USP) Compounding Expert Committee. The Compounding Expert
`
`Committee develops and revises compounding-related general chapters of the USP
`
`describing quality and practice standards for patient-specific formulation of sterile
`
`and nonsterile dosage forms. This USP Expert Committee also develops
`
`compounded preparation monographs containing formulations for both human and
`
`veterinary patients. I also served as a member of the 2010-2015 USP
`
`Compounding Expert Committee during the previous revision cycle.
`
`5.
`
`Prior to my employment at the University of Wisconsin-Madison, I
`
`was the Global Pharmaceutical Development Director / Applications Development
`
`Leader from April 2004 until April 2006 at Dowpharma, a business unit of the
`
`Dow Chemical Company that was dedicated to serving the pharmaceutical and
`
`biopharmaceutical industries. From August 2000 until April 2004, I was
`
`Pharmaceutics Director / Technical Leader of the Pharmaceutics Technologies
`
`group at The Dow Chemical Company.
`
`6.
`
`From February 1997 until August 2000, I was Group Leader, then
`
`Senior Group Leader, for formulation and process development at Glaxo
`
`Wellcome Inc. (now GlaxoSmithKline, Inc.). I began my industrial career in 1989,
`
`– 3 –
`
`Amerigen Ex. 1018, p. 19
`
`

`
`at the predecessor company, Glaxo Inc., as a Senior Scientist. I later progressed to
`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`Research Investigator, and then Research Leader, before becoming a Group
`
`Leader.
`
`7.
`
`I have at least ten publications, three book contributions, and 68
`
`scientific presentations (17 invited).
`
`8.
`
`I have been licensed as a pharmacist in South Carolina from 1985 to
`
`present and in Wisconsin from 2010 to present.
`
`9. My curriculum vitae, Attachment 1, contains further details on my
`
`education and professional experience, as well as all of my publications for the
`
`past 10 years.
`
`10. A list of matters where I have testified is set forth in Attachment 2.
`
`11.
`
`In arriving at my opinions presented in this declaration, I have relied
`
`on my education, experience, and knowledge in the field as well as the materials
`
`identified in the list of exhibits.
`
`12.
`
`I am being compensated at my normal consulting rate for my work.
`
`My compensation is not dependent on, and in no way affects, the substance of my
`
`statements in this Declaration.
`
`13.
`
`I have no financial interest in Petitioner. I similarly have no financial
`
`interest in the ʼ100 patent, or any of the references asserted as prior art thereto.
`
`– 4 –
`
`Amerigen Ex. 1018, p. 20
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`II. LEGAL PRINCIPLES
`
`14.
`
`I have had certain legal principles explained to me by the attorneys of
`
`Husch Blackwell LLP. I am not an expert in law, and I rely on attorneys to be
`
`advised on the legal issues involved in the action.
`
`A. Claim Construction.
`
`15.
`
`I am to interpret the claim terms in an unexpired patent according to
`
`the broadest reasonable construction in light of the specification of the patent in
`
`which they appear. Under that standard, and absent any special definitions, I give
`
`claim terms their ordinary and customary meaning, as would be understood by one
`
`of ordinary skill in the art. Any special definitions for claim terms must be set
`
`forth with reasonable clarity, deliberateness, and precision.
`
`B. Anticipation.
`
`16.
`
`It has been explained to me that a claim is invalid as anticipated under
`
`35 U.S.C. § 102(b) if “the invention was patented or described in a printed
`
`publication in this or a foreign country or in public use or on sale in this country,
`
`more than one year prior to the date of the application for patent in the United
`
`States.” I have also been informed that a claim is invalid as anticipated under 35
`
`U.S.C. § 102(e) if “the invention was described in … an application for patent,
`
`published under section 122(b), by another filed in the United States before the
`
`invention by the applicant for patent ….”
`
`– 5 –
`
`Amerigen Ex. 1018, p. 21
`
`

`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`It has been explained to me that for a claim to be anticipated, all of the
`
`17.
`
`features in the claim must be expressly or inherently present in a single prior art
`
`reference.
`
`18. When a reference is silent about the inherent characteristics, extrinsic
`
`evidence may be used to fill the gap in the reference if the evidence makes clear
`
`that the missing descriptive matter is necessarily present in the thing described in
`
`the reference, such that one of ordinary skill in the art would recognize its
`
`presence. Although the mere possibility or probability will not suffice to fill a gap
`
`in a reference, the gap may be filled if the disclosure is sufficient to show that the
`
`natural result of the disclosed operation is the performance of the questioned
`
`function.
`
`C. Obviousness.
`
`19.
`
`I have been informed that a claim is invalid as obvious under 35
`
`U.S.C. § 103(a) if “the differences between the subject matter sought to be
`
`patented and the prior art are such that the subject matter as a whole would have
`
`been obvious at the time the invention was made to a person having ordinary skill
`
`in the art to which said subject matter pertains.”
`
`20.
`
`I am informed that a person of ordinary skill in the art is “a person of
`
`ordinary creativity, not an automaton.” The person of ordinary skill in the art is to
`
`be assessed based on the educational background and experience of those actively
`
`– 6 –
`
`Amerigen Ex. 1018, p. 22
`
`

`
`working in the field. The level of skill is assessed at the time when the applicant
`
`Declaration of Edmund J. Elder, Jr., Ph.D., R.Ph.
`
`
`developed his technology.
`
`21. The prior art must show that each feature of the claims is shown in the
`
`prior art, as is true for anticipation, but these features may come from more than
`
`one reference. Merely finding the features in the references is insufficient. The
`
`evidence must show that a person of ordinary skill in the art would have had: (1)
`
`reasons to make the claimed subject matter; (2) reasons to use and combine the
`
`references; and (3) a reasonable expectation of success in making the claimed
`
`subject matter with the references.
`
`22. The patent containing the claimed subject matter cannot be used to
`
`guide or prove the obviousness of the claimed subject matter. Only the prior art
`
`and the knowledge of one of ordinary skill in the art at the time the purported
`
`invention was made may be used to prove obviousness.
`
`III. THE ’100 PATENT
`