`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`
`PFIZER INC.,
`Petitioner,
`
`v.
`
`NOVO NORDISK A/S,
`Patent Owner.
`________________
`
`Inter Partes Review No. IPR2020-01252
`United States Patent No. 8,114,833
`Issued: February 14, 2012
`Filed: May 17, 2006
`
`Title: Propylene Glycol-Containing Peptide Formulations Which Are Optimal for
`Productions and for Use in Injection Devices
`________________
`
`
`
`
`
`
`
`
`
`EXPERT DECLARATION OF LAIRD FORREST, PH.D.
`IN SUPPORT OF PETITION FOR INTER PARTES REVIEW
`
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`PO Box 1450
`Alexandria, Virginia 22313–1450
`Submitted Electronically via the Patent Review Processing System
`
`
`
`
`
`
`1
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 1 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`TABLE OF CONTENTS
`
`Page
`
`B.
`C.
`
`QUALIFICATIONS AND BACKGROUND ................................................. 6
`A.
`Education and Experience; Prior Testimony ........................................ 6
`B.
`Bases for Opinions and Materials Considered ....................................10
`C.
`Scope of Work .....................................................................................10
`SUMMARY OF OPINIONS .........................................................................11
`LEGAL STANDARDS .................................................................................12
`PERSON OF ORDINARY SKILL IN THE ART ........................................14
`(cid:55)(cid:43)(cid:40)(cid:3)(cid:1932)(cid:27)(cid:22)(cid:22)(cid:3)(cid:51)(cid:36)(cid:55)(cid:40)(cid:49)(cid:55)(cid:3)(cid:11)(cid:40)(cid:59)(cid:17) 1001) ....................................................................15
`CLAIM CONSTRUCTION ..........................................................................19
`BACKGROUND ...........................................................................................19
`A. GLP-1 Agonists, Including Liraglutide, Were Well Known in the
`Art ........................................................................................................19
`Parenteral Peptide Dosage Forms .......................................................20
`Stability of Peptide Formulations and Selection of Excipients ..........30
`i.
`Use of Propylene Glycol in Peptide Formulations ...................32
`ii.
`Propylene Glycol is Safe ...........................................................34
`iii.
`Propylene Glycol’s Advantages Over Other Isotonic Agents ..34
`SCOPE AND CONTENT OF THE PRIOR ART REFERENCES ..............38
`A.
`(cid:41)(cid:79)(cid:76)(cid:81)(cid:78)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:23)(cid:12) ..................................................................................38
`B.
`(cid:37)(cid:72)(cid:87)(cid:93)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:24)(cid:12) ...................................................................................48
`C.
`Other Art That Informs the Person of Ordinary Skill’s Knowledge ..51
`i.
`(cid:56)(cid:17)(cid:54)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:25)(cid:15)(cid:21)(cid:25)(cid:27)(cid:15)(cid:22)(cid:23)(cid:22)(cid:3)(cid:11)(cid:179)(cid:46)(cid:81)(cid:88)(cid:71)(cid:86)(cid:72)(cid:81)(cid:3)(cid:44)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:12) ..............51
`ii.
`(cid:40)(cid:88)(cid:85)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:17)(cid:3)(cid:36)(cid:83)(cid:83)(cid:17)(cid:3)(cid:51)(cid:88)(cid:69)(cid:17)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:40)(cid:51)(cid:19)(cid:28)(cid:21)(cid:22)(cid:28)(cid:24)(cid:19)(cid:3)(cid:11)(cid:179)(cid:44)(cid:69)(cid:68)(cid:85)(cid:68)(cid:78)(cid:76)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)
`1007) .........................................................................................51
`(cid:51)(cid:82)(cid:90)(cid:72)(cid:79)(cid:79)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:27)(cid:12) .....................................................................52
`(cid:40)(cid:83)(cid:83)(cid:72)(cid:85)(cid:86)(cid:82)(cid:81)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:28)(cid:12) .................................................................53
`(cid:45)(cid:68)(cid:70)(cid:82)(cid:69)(cid:86)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:20)(cid:20)(cid:12) ......................................................................53
`
`iii.
`iv.
`v.
`
`
`2
`
`
`
`
`
`
`1.
`
`2.
`3.
`4.
`5.
`6.
`7.
`
`8.
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 2 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`vi.
`
`(cid:44)(cid:81)(cid:87)(cid:182)(cid:79)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:51)(cid:88)(cid:69)(cid:17)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:58)(cid:50)(cid:3)(cid:20)(cid:28)(cid:28)(cid:28)(cid:18)(cid:19)(cid:23)(cid:19)(cid:26)(cid:27)(cid:27)(cid:3)(cid:11)(cid:179)(cid:60)(cid:82)(cid:88)(cid:81)(cid:74)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)
`1025) .........................................................................................54
`(cid:44)(cid:81)(cid:87)(cid:182)(cid:79)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:51)(cid:88)(cid:69)(cid:17)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:58)(cid:50)(cid:3)(cid:19)(cid:22)(cid:18)(cid:19)(cid:26)(cid:21)(cid:20)(cid:28)(cid:24)(cid:3)(cid:11)(cid:179)(cid:46)(cid:75)(cid:68)(cid:81)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:20)(cid:23)(cid:12) .....54
`vii.
`(cid:44)(cid:81)(cid:87)(cid:182)(cid:79)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:51)(cid:88)(cid:69)(cid:17)(cid:3)(cid:49)(cid:50)(cid:17)(cid:3)(cid:58)(cid:50)(cid:3)(cid:28)(cid:24)(cid:18)(cid:19)(cid:21)(cid:21)(cid:24)(cid:25)(cid:19)(cid:3)(cid:11)(cid:179)(cid:39)(cid:76)(cid:91)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:20)(cid:28)(cid:12) .......55
`viii.
`ix. (cid:56)(cid:17)(cid:54)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:25)(cid:15)(cid:23)(cid:24)(cid:27)(cid:15)(cid:28)(cid:21)(cid:23)(cid:3)(cid:11)(cid:179)(cid:46)(cid:81)(cid:88)(cid:71)(cid:86)(cid:72)(cid:81)(cid:3)(cid:44)(cid:44)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:21)(cid:19)(cid:12) .............56
`x.
`(cid:44)(cid:81)(cid:87)(cid:182)(cid:79)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:51)(cid:88)(cid:69)(cid:17)(cid:3)(cid:49)(cid:50)(cid:17)(cid:3)(cid:58)(cid:50)(cid:3)(cid:19)(cid:19)(cid:18)(cid:19)(cid:22)(cid:26)(cid:19)(cid:28)(cid:27)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:21)(cid:20)(cid:12) .....................56
`xi. (cid:43)(cid:68)(cid:81)(cid:71)(cid:69)(cid:82)(cid:82)(cid:78)(cid:3)(cid:82)(cid:73)(cid:3)(cid:51)(cid:75)(cid:68)(cid:85)(cid:80)(cid:68)(cid:70)(cid:72)(cid:88)(cid:87)(cid:76)(cid:70)(cid:68)(cid:79)(cid:3)(cid:40)(cid:91)(cid:70)(cid:76)(cid:83)(cid:76)(cid:72)(cid:81)(cid:87)(cid:86)(cid:3)(cid:21)(cid:19)(cid:19)(cid:19)(cid:15)(cid:3)(cid:21)(cid:19)(cid:19)(cid:22)(cid:3)(cid:11)(cid:40)(cid:91)(cid:86)(cid:17)(cid:3)
`1022-1023) ................................................................................57
`xii. (cid:49)(cid:68)(cid:76)(cid:79)(cid:3)(cid:9)(cid:3)(cid:36)(cid:78)(cid:72)(cid:85)(cid:86)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:21)(cid:23)(cid:12) ...........................................................57
`xiii. (cid:37)(cid:82)(cid:81)(cid:87)(cid:72)(cid:80)(cid:83)(cid:82)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:21)(cid:25)(cid:12) ................................................................60
`xiv. (cid:42)(cid:68)(cid:87)(cid:79)(cid:76)(cid:81)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:21)(cid:26)(cid:12).......................................................................61
`xv. (cid:53)(cid:72)(cid:80)(cid:76)(cid:81)(cid:74)(cid:87)(cid:82)(cid:81)(cid:182)(cid:86)(cid:3)(cid:20)(cid:28)(cid:28)(cid:19)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:20)(cid:22)(cid:12) ...................................................64
`xvi. (cid:54)(cid:87)(cid:88)(cid:85)(cid:76)(cid:86)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:23)(cid:25)(cid:12) .......................................................................66
`xvii. (cid:38)(cid:75)(cid:68)(cid:81)(cid:74)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:24)(cid:28)(cid:12) ......................................................................66
`xviii. (cid:56)(cid:17)(cid:54)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:23)(cid:15)(cid:23)(cid:21)(cid:24)(cid:15)(cid:22)(cid:23)(cid:25)(cid:3)(cid:11)(cid:179)(cid:43)(cid:82)(cid:85)(cid:79)(cid:76)(cid:81)(cid:74)(cid:87)(cid:82)(cid:81)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:25)(cid:22)(cid:12) .............67
`xix. (cid:56)(cid:17)(cid:54)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:25)(cid:15)(cid:21)(cid:19)(cid:26)(cid:15)(cid:25)(cid:27)(cid:23)(cid:3)(cid:11)(cid:179)(cid:36)(cid:69)(cid:72)(cid:85)(cid:74)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:25)(cid:23)(cid:12) .....................68
`xx. (cid:56)(cid:17)(cid:54)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:25)(cid:15)(cid:23)(cid:23)(cid:19)(cid:15)(cid:23)(cid:25)(cid:19)(cid:3)(cid:11)(cid:179)(cid:42)(cid:88)(cid:85)(cid:81)(cid:92)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:25)(cid:24)(cid:12) .....................68
`xxi. Additional Prior Art References and Knowledge .....................69
`UNPATENTABILITY OF T(cid:43)(cid:40)(cid:3)(cid:1932)(cid:27)(cid:22)(cid:22)(cid:3)(cid:51)(cid:36)(cid:55)(cid:40)(cid:49)(cid:55) ..........................................69
`A.
`Claims 1-(cid:20)(cid:24)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:1932)(cid:27)(cid:22)(cid:22)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:58)(cid:72)(cid:85)(cid:72)(cid:3)(cid:36)(cid:81)(cid:87)(cid:76)(cid:70)(cid:76)(cid:83)(cid:68)(cid:87)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:82)(cid:85)(cid:3)(cid:58)(cid:82)(cid:88)(cid:79)(cid:71)(cid:3)
`Have Been Obvious Over Flink ..........................................................69
`i.
`Claim 1 Was Anticipated by or Would have Been Obvious
`Over Flink .................................................................................69
`1.
`Flink disclosed the GLP-1 agonist .................................71
`2.
`Flink disclosed the claimed buffer .................................71
`3.
`Flink disclosed the claimed isotonic agent .....................74
`4.
`It would have been obvious to select propylene glycol ..74
`5.
`Calculating an appropriate concentration of propylene
`glycol was obvious .........................................................77
`Flink disclosed the claimed pH ......................................80
`
`6.
`
`
`3
`
`
`
`
`
`9.
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 3 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`ii.
`
`v.
`
`x.
`
`ii.
`
`B.
`
`
`
`Claims 2-4 Were Anticipated by or Would Have Been
`Obvious Over Flink ...................................................................81
`iii. Claims 5-7 Were Anticipated by or Would Have Been
`Obvious Over Flink ...................................................................81
`iv. Claims 8 and 9 Were Anticipated by or Would Have Been
`Obvious Over Flink ...................................................................82
`Claim 10 Was Anticipated by or Would Have Been Obvious
`Over Flink .................................................................................82
`vi. Claim 11 Was Anticipated by or Would Have Been Obvious
`Over Flink .................................................................................83
`vii. Claim 12 Was Anticipated by or Would Have Been Obvious
`over Flink ..................................................................................84
`viii. Claim 13 Was Anticipated by or Would Have Been Obvious
`Over Flink .................................................................................84
`ix. Claim 14 Was Anticipated by or Would Have Been Obvious
`Over Flink .................................................................................85
`Claim 15 Was Anticipated by or Would Have Been Obvious
`Over Flink .................................................................................86
`Claims 1-(cid:22)(cid:20)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:1932)(cid:27)(cid:22)(cid:22)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:58)(cid:82)(cid:88)(cid:79)(cid:71)(cid:3)(cid:43)(cid:68)(cid:89)(cid:72)(cid:3)(cid:37)(cid:72)(cid:72)(cid:81)(cid:3)(cid:50)(cid:69)(cid:89)(cid:76)(cid:82)(cid:88)(cid:86)(cid:3)(cid:50)(cid:89)(cid:72)(cid:85)(cid:3)
`Flink in View of Betz ..........................................................................87
`i.
`Claims 1-15 Would Have Been Obvious Over Flink in View
`of Betz .......................................................................................87
`1.
`The common problem of peptide instability in
`formulations ....................................................................90
`Flink taught that mannitol should not be used in
`formulations having a pH of 7.4 .....................................92
`It would have been obvious to solve the problem of
`precipitation with propylene glycol ................................93
`Claim 16 Would Have Been Obvious Over Flink in View of
`Betz ...........................................................................................95
`iii. Claims 17-19 Would Have Been Obvious Over Flink in
`View of Betz .............................................................................97
`iv. Claims 20-22 Would Have Been Obvious Over Flink in
`View of Betz .............................................................................97
`
`4
`
`2.
`
`3.
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 4 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`v.
`
`Claims 23, 26, and 29 Would Have Been Obvious Over
`Flink in View of Betz ................................................................98
`vi. Claims 24, 27, and 30 Would Have Been Obvious Over
`Flink in View of Betz ................................................................99
`vii. Claims 25, 28, and 31 Would Have Been Obvious Over
`Flink in View of Betz ..............................................................101
`10. NO SECONDARY CONSIDERATONS OVERCOME PRIMA FACIE
`OBVIOUSNESS OF THE CLAIMED INVENTIONS ..............................102
`A.
`(cid:55)(cid:75)(cid:72)(cid:3)(cid:48)(cid:72)(cid:87)(cid:75)(cid:82)(cid:71)(cid:86)(cid:3)(cid:53)(cid:72)(cid:70)(cid:76)(cid:87)(cid:72)(cid:71)(cid:3)(cid:76)(cid:81)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:1932)(cid:27)(cid:22)(cid:22)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:51)(cid:85)(cid:82)(cid:71)(cid:88)(cid:70)(cid:72)(cid:3)(cid:49)(cid:82)(cid:3)(cid:56)(cid:81)(cid:72)(cid:91)(cid:83)(cid:72)(cid:70)(cid:87)(cid:72)(cid:71)(cid:3)
`Results ...............................................................................................102
`There Was No Long-Felt But Unmet Need ......................................103
`There Was No Industry Skepticism ..................................................104
`Copying By Generic Drug Makers Is Irrelevant ...............................104
`A Blocking Patent Existed at the Time of the Claimed Invention ...104
`
`B.
`C.
`D.
`E.
`
`
`
`
`
`
`
`
`
`
`5
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 5 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`1. My name is Laird Forrest, Ph.D. I have been retained by counsel for
`
`Pfizer Inc. (cid:11)(cid:179)Pfizer(cid:180)(cid:12)(cid:17)(cid:3)(cid:44)(cid:3)(cid:88)(cid:81)(cid:71)(cid:72)(cid:85)(cid:86)(cid:87)(cid:68)(cid:81)(cid:71)(cid:3)(cid:87)(cid:75)(cid:68)(cid:87)(cid:3)Pfizer intends to petition for inter partes
`
`(cid:85)(cid:72)(cid:89)(cid:76)(cid:72)(cid:90)(cid:3)(cid:11)(cid:179)(cid:44)(cid:51)(cid:53)(cid:180)(cid:12)(cid:3)(cid:82)(cid:73)(cid:3)(cid:56)(cid:17)(cid:54)(cid:17)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:27)(cid:15)(cid:20)(cid:20)(cid:23)(cid:15)(cid:27)(cid:22)(cid:22)(cid:3)(cid:11)(cid:179)(cid:87)(cid:75)(cid:72)(cid:3)(cid:182)(cid:27)(cid:22)(cid:22)(cid:3)(cid:83)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:180)(cid:12)(cid:15)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:20)(cid:15)(cid:3)(cid:90)(cid:75)(cid:76)(cid:70)(cid:75)(cid:3)(cid:76)(cid:86)(cid:3)
`
`assigned to Novo Nordisk A/S. I also understand that, in the IPR petition, Pfizer
`
`will request that the United States Patent and Trademark Office cancel all claims of
`
`the ’833 patent as unpatentable. I submit this expert declaration to address and
`
`support Pfizer’s IPR petition for the ’833 patent.
`
`1. QUALIFICATIONS AND BACKGROUND
`A. Education and Experience; Prior Testimony
`2.
` I am currently a Professor in the Department of Pharmaceutical
`
`Chemistry at the University of Kansas in Lawrence, Kansas, a position I have held
`
`since 2017. I am also Professor in the Bioengineering Center, a position I have held
`
`since 2011, and Professor in the Department of Medicinal Chemistry, a position I
`
`have held since 2015, both also at the University of Kansas. I have been a faculty at
`
`the University of Kansas since 2007.
`
`3.
`
`I received a Bachelor of Science in Chemical Engineering from Auburn
`
`University in 1998, a Master of Science in Chemical Engineering from the
`
`University of Illinois in 2001, and a Ph.D. in Chemical and Biomolecular
`
`Engineering from the University of Illinois in 2003. I was a Postdoctoral Fellow in
`
`the Division of Pharmaceutical Sciences at the University of Wisconsin, Madison,
`
`
`
`
`6
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 6 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`from 2004 to 2006. In 2006, I became Adjunct Assistant Professor in the Department
`
`of Pharmaceutical Sciences at Washington State University, a position I held until
`
`2011. In 2007, I accepted a position as Assistant Professor in the Department of
`
`Pharmaceutical Chemistry at the University of Kansas. I was promoted to Associate
`
`Professor at the University of Kansas in 2013. I was then promoted to the rank of
`
`Professor in 2017.
`
`4.
`
`Since 2009, I have been a Member of the Scientific and Medical
`
`Advisory Board of Exogenesis Corporation, which develops nanoscale surface
`
`modifications for implantable medical devices. I am the co-founder of HylaPharm
`
`LLC, founded in 2011, which specializes in reformulation of anti-cancer
`
`chemotherapeutics by modification of the delivery route and pharmacokinetics.
`
`Also, I am a co-founder of Hafion LLC, founded in 2016, which specializes in
`
`development of vaccines, and Aerobyx LLC, founded in 2017, which specializes in
`
`the development of medications for treatment of neurological and metabolic disease.
`
`In addition, I am a co-founder of Vesarex, founded in 2018, which specializes in the
`
`development of ultrasound imaging devices and contrast agents. My research toward
`
`drug formulation has been competitively funded by multiple awards from the
`
`National Institutes of Health and the National Cancer Institute, the National Institute
`
`of Allergy and Infectious Disease, the American Cancer Society, the Department of
`
`
`
`
`7
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 7 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`Defense, Susan G. Komen Race for the Cure, and the Pharmaceutical Research and
`
`(cid:48)(cid:68)(cid:81)(cid:88)(cid:73)(cid:68)(cid:70)(cid:87)(cid:88)(cid:85)(cid:72)(cid:85)(cid:86)(cid:3) (cid:82)(cid:73)(cid:3) (cid:36)(cid:80)(cid:72)(cid:85)(cid:76)(cid:70)(cid:68)(cid:3) (cid:41)(cid:82)(cid:88)(cid:81)(cid:71)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3) (cid:11)(cid:179)(cid:51)(cid:75)(cid:53)(cid:48)(cid:36)(cid:180)(cid:12)(cid:15)(cid:3) (cid:68)(cid:80)(cid:82)(cid:81)(cid:74)(cid:3)(cid:82)(cid:87)(cid:75)(cid:72)(cid:85)(cid:86)(cid:17)(cid:3) (cid:44)(cid:81)(cid:3) (cid:68)(cid:71)(cid:71)(cid:76)(cid:87)(cid:76)(cid:82)(cid:81)(cid:15)(cid:3) (cid:44)(cid:3)
`
`have been funded (cid:69)(cid:92)(cid:3) (cid:87)(cid:75)(cid:72)(cid:3) (cid:41)(cid:82)(cid:82)(cid:71)(cid:3) (cid:68)(cid:81)(cid:71)(cid:3) (cid:39)(cid:85)(cid:88)(cid:74)(cid:3) (cid:36)(cid:71)(cid:80)(cid:76)(cid:81)(cid:76)(cid:86)(cid:87)(cid:85)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3) (cid:11)(cid:179)(cid:41)(cid:39)(cid:36)(cid:180)(cid:12)(cid:3) (cid:87)(cid:82)(cid:3) (cid:71)(cid:72)(cid:89)(cid:72)(cid:79)(cid:82)(cid:83)(cid:3)
`
`methodologies for the in vitro determination of bioequivalence in follow-on complex
`
`botanical and biosimilar drug formulations.
`
`5.
`
`I have received many awards and honors, including the Baxendale
`
`(cid:44)(cid:81)(cid:81)(cid:82)(cid:89)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3)(cid:36)(cid:90)(cid:68)(cid:85)(cid:71)(cid:3)(cid:11)(cid:21)(cid:19)(cid:20)(cid:25)(cid:12)(cid:15)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:56)(cid:81)(cid:76)(cid:89)(cid:72)(cid:85)(cid:86)(cid:76)(cid:87)(cid:92)(cid:3)(cid:82)(cid:73)(cid:3)(cid:46)(cid:68)(cid:81)(cid:86)(cid:68)(cid:86)(cid:3)(cid:47)(cid:72)(cid:68)(cid:71)(cid:76)(cid:81)(cid:74)(cid:3)(cid:47)(cid:76)(cid:74)(cid:75)(cid:87)(cid:3)(cid:68)(cid:90)(cid:68)(cid:85)(cid:71)(cid:3)(cid:11)(cid:21)(cid:19)(cid:20)(cid:23)(cid:12)(cid:15)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)
`
`Japan So(cid:70)(cid:76)(cid:72)(cid:87)(cid:92)(cid:3) (cid:73)(cid:82)(cid:85)(cid:3) (cid:51)(cid:85)(cid:82)(cid:80)(cid:82)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3) (cid:82)(cid:73)(cid:3) (cid:54)(cid:70)(cid:76)(cid:72)(cid:81)(cid:70)(cid:72)(cid:3) (cid:57)(cid:76)(cid:86)(cid:76)(cid:87)(cid:76)(cid:81)(cid:74)(cid:3) (cid:54)(cid:70)(cid:75)(cid:82)(cid:79)(cid:68)(cid:85)(cid:3) (cid:41)(cid:72)(cid:79)(cid:79)(cid:82)(cid:90)(cid:3) (cid:11)(cid:21)(cid:19)(cid:20)(cid:19)(cid:12)(cid:15)(cid:3) (cid:87)(cid:75)(cid:72)(cid:3)
`
`(cid:36)(cid:80)(cid:72)(cid:85)(cid:76)(cid:70)(cid:68)(cid:81)(cid:3) (cid:38)(cid:68)(cid:81)(cid:70)(cid:72)(cid:85)(cid:3) (cid:54)(cid:82)(cid:70)(cid:76)(cid:72)(cid:87)(cid:92)(cid:3) (cid:53)(cid:72)(cid:86)(cid:72)(cid:68)(cid:85)(cid:70)(cid:75)(cid:3) (cid:54)(cid:70)(cid:75)(cid:82)(cid:79)(cid:68)(cid:85)(cid:3) (cid:11)(cid:21)(cid:19)(cid:19)(cid:27)(cid:3) (cid:87)(cid:82)(cid:3) (cid:21)(cid:19)(cid:20)(cid:21)(cid:12)(cid:15)(cid:3) (cid:87)(cid:75)(cid:72)(cid:3) (cid:36)(cid:80)(cid:72)(cid:85)(cid:76)(cid:70)(cid:68)(cid:81)(cid:3)
`
`(cid:36)(cid:86)(cid:86)(cid:82)(cid:70)(cid:76)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3) (cid:82)(cid:73)(cid:3) (cid:38)(cid:82)(cid:79)(cid:79)(cid:72)(cid:74)(cid:72)(cid:86)(cid:3) (cid:82)(cid:73)(cid:3) (cid:51)(cid:75)(cid:68)(cid:85)(cid:80)(cid:68)(cid:70)(cid:92)(cid:15)(cid:3) (cid:49)(cid:72)(cid:90)(cid:3) (cid:44)(cid:81)(cid:89)(cid:72)(cid:86)(cid:87)(cid:76)(cid:74)(cid:68)(cid:87)(cid:82)(cid:85)(cid:86)(cid:3) (cid:36)(cid:90)(cid:68)(cid:85)(cid:71)(cid:3) (cid:11)(cid:21)(cid:19)(cid:19)(cid:26)(cid:12)(cid:15)(cid:3) (cid:68)(cid:81)(cid:71)(cid:3) (cid:87)(cid:75)(cid:72)(cid:3)
`
`(cid:51)(cid:75)(cid:53)(cid:48)(cid:36)(cid:3)(cid:41)(cid:82)(cid:88)(cid:81)(cid:71)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3)(cid:51)(cid:82)(cid:86)(cid:87)(cid:71)(cid:82)(cid:70)(cid:87)(cid:82)(cid:85)(cid:68)(cid:79)(cid:3)(cid:41)(cid:72)(cid:79)(cid:79)(cid:82)(cid:90)(cid:3)(cid:11)(cid:21)(cid:19)(cid:19)(cid:25)), among others.
`
`6.
`
`I am currently or have been in the past a member of various professional
`
`societies, including the American Association for Cancer Research, the American
`
`Association of Pharmaceutical Scientists, and the American Institute of Chemical
`
`Engineers. I serve or have served on numerous scientific review panels for the
`
`National Institutes of Health, the American Cancer Society, and the Association for
`
`(cid:44)(cid:81)(cid:87)(cid:72)(cid:85)(cid:81)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:68)(cid:79)(cid:3)(cid:38)(cid:68)(cid:81)(cid:70)(cid:72)(cid:85)(cid:3)(cid:53)(cid:72)(cid:86)(cid:72)(cid:68)(cid:85)(cid:70)(cid:75)(cid:3)(cid:11)(cid:56)(cid:81)(cid:76)(cid:87)(cid:72)(cid:71)(cid:3)(cid:46)(cid:76)(cid:81)(cid:74)(cid:71)(cid:82)(cid:80)(cid:12)(cid:17)(cid:3)(cid:44)(cid:3)(cid:68)(cid:80)(cid:3)(cid:68)(cid:3)(cid:86)(cid:87)(cid:68)(cid:81)(cid:71)(cid:76)(cid:81)(cid:74)(cid:3)(cid:80)(cid:72)(cid:80)(cid:69)(cid:72)(cid:85)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)
`
`American Cancer Society review panel on Cancer Drug Development.
`
`
`
`
`8
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 8 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`7.
`
`I have authored more than 90 peer-reviewed journal articles and 5 book
`
`chapters. I have also edited 2 special journal issues on drug delivery and a book on
`
`drug delivery and formulation.
`
`8.
`
`I have taught drug formulation and biopharmaceutics, including all
`
`aspects of drug excipient choice and the effects of excipient modification on drug
`
`pharmacokinetics, ionic equilibrium, drug chemical stability, drug dissolution, and
`
`drug absorption, to clinical pharmacy students and graduate students studying
`
`pharmaceutical sciences since 2007.
`
`9.
`
`I have experience in all aspects of parenteral, topical, and oral drug
`
`formulation and pharmacokinetics through my research and teaching. Additionally,
`
`as part of my work with HylaPharm, Exogenesis Inc., Atrin Pharmaceutics, and
`
`Akari Therapeutics Inc., I have worked on pharmaceutical formulations for
`
`intramuscular, subcutaneous, intravenous, topical, and oral formulation.
`
`10.
`
`In the past six years, I have testified in the following litigations:
`
`(cid:120) Merck Sharp & Dohme Corp. v. Savior Lifetec Corp., No. 5:15-cv-
`
`00415-(cid:55)(cid:58)(cid:37)(cid:3)(cid:11)(cid:40)(cid:17)(cid:39)(cid:17)(cid:49)(cid:17)(cid:38)(cid:17)(cid:12)(cid:30)
`
`(cid:120) Medac Pharma, Inc. et al. v. Antares Pharma Inc. et al., No. 1:14-cv-
`
`01498-JBS-(cid:46)(cid:48)(cid:58)(cid:3)(cid:11)(cid:39)(cid:17)(cid:49)(cid:17)(cid:45)(cid:17)(cid:12)(cid:30)
`
`(cid:120) Halozyme, Inc. v. Joseph Matal (on behalf of USPTO), No. 1:16-cv-
`
`(cid:20)(cid:24)(cid:27)(cid:19)(cid:3)(cid:11)E.D. Va.);
`
`
`
`
`9
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 9 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`(cid:120) Bracco Diagnostics v. Maia Pharm., Inc., No. 3:17-cv-(cid:20)(cid:22)(cid:20)(cid:24)(cid:20)(cid:3)(cid:11)(cid:39)(cid:17)(cid:49)(cid:17)(cid:45)(cid:17)(cid:12)(cid:30)
`
`(cid:120) Horizon Medicines LLC v. Dr. Reddy’s Labs. Inc., No. 2:15-cv-03324-
`
`SRC-(cid:38)(cid:47)(cid:58)(cid:3)(cid:11)(cid:39)(cid:17)(cid:49)(cid:17)(cid:45)(cid:17)(cid:12)(cid:3)(cid:11)(cid:70)(cid:82)(cid:81)(cid:86)(cid:82)(cid:79)(cid:76)(cid:71)(cid:68)(cid:87)(cid:72)(cid:71)(cid:12); and
`
`(cid:120) Cydex Pharmaceuticals, Inc., v. Alembic Global Holding SA, Alembic
`
`Pharmaceuticals, Ltd., and Alembic Pharmaceuticals, Inc., No. 1:19-
`
`CV-00956-(cid:47)(cid:51)(cid:54)(cid:3)(cid:11)(cid:39)(cid:17)N.J.)
`
`11. My curriculum vitae, which describes my experience and background
`
`in more detail, is attached as Exhibit A.
`
`B.
`Bases for Opinions and Materials Considered
`12. Exhibit B includes a list of the materials I considered, in addition to my
`
`experience, education, and training, in providing the opinions contained in this
`
`declaration.
`
`C.
`13.
`
`Scope of Work
`I have been retained by Pfizer as a technical expert to provide various
`
`opinions regarding the ’833 patent. I am being compensated for my time at my
`
`standard consulting rate of $600/hour. Neither the amount of my compensation nor
`
`the fact that I am being compensated has altered the opinions that I have given in
`
`this Declaration. My compensation is in no way dependent on the outcome of this
`
`proceeding. I do not have any current or past affiliation with Novo Nordisk A/S, or
`
`any of its affiliates presently known to me, or the named inventors on the ’833 patent.
`
`
`
`
`10
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 10 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`2.
`
`SUMMARY OF OPINIONS
`14.
`In my view, claims 1-15 of the ’833 patent were anticipated by
`
`(cid:44)(cid:81)(cid:87)(cid:72)(cid:85)(cid:81)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:68)(cid:79)(cid:3)(cid:51)(cid:68)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:51)(cid:88)(cid:69)(cid:79)(cid:76)(cid:70)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3)(cid:49)(cid:82)(cid:17)(cid:3)(cid:58)(cid:50)(cid:3)(cid:21)(cid:19)(cid:19)(cid:22)(cid:18)(cid:19)(cid:19)(cid:19)(cid:21)(cid:20)(cid:22)(cid:25)(cid:3)(cid:87)(cid:82)(cid:3)(cid:41)(cid:79)(cid:76)(cid:81)(cid:78)(cid:3)(cid:72)(cid:87)(cid:3)(cid:68)(cid:79)(cid:17)(cid:3)(cid:11)(cid:179)(cid:41)(cid:79)(cid:76)(cid:81)(cid:78)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)
`
`1004), as described in detail below. Flink’s claim 14 disclosed, in the context of the
`
`specification, each element of the inventions claimed in claims 1-15 of the ’833
`
`patent.
`
`15. Also, claims 1-15 of the ’833 patent would have been obvious over
`
`Flink, as described in detail below. In short, to the extent Flink would have been
`
`viewed as not anticipating the inventions claimed in the ’833 patent, the inventions
`
`would have been obvious to a person of ordinary skill in the art because the POSA
`
`would have been motivated to combine the claimed elements with a reasonable
`
`expectation of success.
`
`16. Additionally, claims 1-31 of the ’833 patent would have been obvious
`
`over Flink in view of International Patent Publication No. WO 2004/0004781 to Betz
`
`(cid:68)(cid:81)(cid:71)(cid:3)(cid:54)(cid:87)(cid:72)(cid:89)(cid:72)(cid:81)(cid:86)(cid:3)(cid:11)(cid:179)(cid:37)(cid:72)(cid:87)(cid:93)(cid:180)(cid:12)(cid:3)(cid:11)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:24)(cid:12)(cid:15)(cid:3)(cid:68)(cid:86)(cid:3)(cid:71)(cid:72)(cid:86)(cid:70)(cid:85)(cid:76)(cid:69)(cid:72)(cid:71)(cid:3)(cid:76)(cid:81)(cid:3)(cid:71)(cid:72)(cid:87)(cid:68)(cid:76)(cid:79)(cid:3)(cid:69)(cid:72)(cid:79)(cid:82)(cid:90)(cid:17)(cid:3)(cid:55)(cid:82)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:72)(cid:91)(cid:87)(cid:72)(cid:81)(cid:87)(cid:3)(cid:41)(cid:79)(cid:76)(cid:81)(cid:78)(cid:3)
`
`would have been viewed as neither anticipating nor rendering obvious the claims of
`
`the ’833 patent, a POSA would have understood from Betz to use propylene glycol
`
`in the GLP-1 formulation disclosed in Flink, with a reasonable expectation of
`
`success.
`
`
`
`
`11
`
`
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1002, p. 11 of 133
`
`

`

`IPR2020-01252 Patent No. 8,114,833 B2
`
`17. Finally, there are no apparent secondary considerations supporting
`
`nonobviousness of the claims. There is no evidence of unexpected results in view
`
`of the prior art, which also satisfied any need for the claimed invention. Further,
`
`there is no evidence of industry skepticism of the claimed invention, and any
`
`allegation that the invention is nonobvious because it was copied does not weight in
`
`this context. Finally, a blocking patent existed at the time of the claimed invention,
`
`which would have dissuaded anyone from developing the claimed formulations and
`
`methods, and reduces the weight to be given to any secondary considerations
`
`asserted in favor of patentability. I reserve the right to address any secondary
`
`considerations put forth by Patent Owner in any later response to this declar