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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS INC., DR. REDDY’S LABORATORIES, INC.
`and DR. REDDY’S LABORATORIES, LTD.
`Petitioner,
`v.
`
`NOVO NORDISK A/S,
`Patent Owner.
`
`
`
`
`
`
`
`
`Case No. IPR2023-007241
`Patent No. 10,335,462
`
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`REPLY DECLARATION OF WILLIAM J. JUSKO, PH.D.
`
`
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`1 IPR2024-00009 (Dr. Reddy’s Laboratories) has been joined with this proceeding.
`
`
`
`MPI EXHIBIT 1301 PAGE 1
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`

`

`TABLE OF CONTENTS
`
`
`Page
`
`
`SUMMARY OF OPINIONS ........................................................................ 13
`I.
`LEGAL STANDARDS ................................................................................ 15
`II.
`III. PERSON OF ORDINARY SKILL IN THE ART ....................................... 19
`IV. CLAIM CONSTRUCTION ......................................................................... 21
`V.
`THE ’462 PATENT ...................................................................................... 23
`VI. REFERENCES IN THE ART ...................................................................... 24
`SCOPE OF THE PRIOR ART .................................................................... 24
`A.
`1. WO421 (EX1011) .................................................................... 25
`2.
`Lovshin (EX1012).................................................................... 28
`3.
`NCT657 (EX1013) ................................................................... 30
`4.
`NCT773 (EX1014) ................................................................... 31
`5. WO537 (EX1015) .................................................................... 32
`6.
`Lund (EX1035) ........................................................................ 33
`7.
`Seino (EX1038)........................................................................ 36
`8.
`Tamimi (EX1047) .................................................................... 38
`9.
`FDA Exposure Response 2003 (EX1048) ............................... 40
`B. ADDITIONAL REFERENCES RELIED UPON BY DR. ROSENSTOCK ......... 41
`1.
`Knight (EX2005)...................................................................... 41
`2.
`Arrowsmith (EX2006) ............................................................. 46
`3.
`Novo Nordisk Annual Report 2010 (EX2065) ........................ 52
`4.
`Report on the Deliberation Results (EX2067) ......................... 59
`5.
`Kim (EX2066) .......................................................................... 62
`6.
`Rosenstock 2009 (EX2062) ..................................................... 63
`7. Madsbad 2004 (EX2075) ......................................................... 66
`8.
`Nordqvist (EX2061) ................................................................. 73
`VII. PURPORTED FAILED AND WITHDRAWN GLP-1 RECEPTOR
`AGONISTS ................................................................................................... 76
`
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`-2-
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`MPI EXHIBIT 1301 PAGE 2
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`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`b.
`
`(ii)
`
`
`VIII. UNPATENTABILITY OF THE ’462 PATENT ......................................... 84
`A. GROUND 1: WO421 ANTICIPATED CLAIMS 1-3 OF THE ’462
`PATENT ................................................................................................ 84
`1. WO421 anticipated claim 1 ..................................................... 84
`a.
`A skilled artisan would have understood that the 0.1 – 1.6
`mg range in WO421 discloses the 1.0 mg dose and would
`have immediately envisaged the 1.0 mg dose ......................... 85
`The 1.0 mg dose is not critical .............................................. 96
`(i)
`The claims do not require any particular level of
`efficacy .................................................................. 98
`The claims do not require any particular level of
`tolerability ............................................................ 102
`2. WO421 anticipated claims 2 and 3 ........................................ 105
`B. GROUND 2: LOVSHIN ANTICIPATED CLAIMS 1-3 OF THE ’462
`PATENT .............................................................................................. 107
`1.
`Lovshin anticipated claim 1 ................................................... 107
`a.
`A skilled artisan would have understood that the 0.1 – 1.6
`mg range in Lovshin discloses the 1.0 mg dose and would
`have immediately envisaged the 1.0 mg dose ....................... 107
`The 1 mg dose is not critical .............................................. 112
`b.
`Lovshin anticipated claims 2 and 3 ........................................ 112
`2.
`C. GROUND 3-5: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE
`BEEN OBVIOUS .................................................................................. 114
`1.
`A skilled artisan would have been motivated to pursue a
`method for treating type 2 diabetes with a once weekly
`1.0 mg dose of semaglutide ................................................... 114
`A skilled artisan would have had a reasonable
`expectation of success pursuing a method for treating
`type 2 diabetes with a once weekly 1.0 mg dose of
`semaglutide ............................................................................ 124
`
`2.
`
`
`
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`-3-
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`MPI EXHIBIT 1301 PAGE 3
`
`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`a.
`
`b.
`
`(ii)
`
`A skilled artisan would have had a reasonable expectation
`of success in optimizing to reach a method for treating type
`2 diabetes with a once weekly 1.0 mg dose of semaglutide ..... 126
`The claims do not require that the once-weekly 1.0 mg dose
`of semaglutide have a particular level of efficacy or
`tolerability ...................................................................... 135
`(i)
`A skilled artisan would not have needed to have
`reported results from a semaglutide clinical trial to
`have had a reasonable expectation of success ............. 138
`A skilled artisan would not have needed to know
`the specific shape of the semaglutide dose response
`curve to have had a reasonable expectation of
`success ................................................................. 144
`(iii) That the semaglutide phase III trial was “on hold”
`would not have dissuaded a skilled artisan from
`pursuing the claimed method ................................... 150
`Ground 3: Claims 1-10 of the ’462 Patent Would Have
`Been Obvious Over WO421 .................................................. 151
`a.
`Claim 1 would have been obvious over WO ’421
`considering the ’424 publication ......................................... 151
`Claims 2-3 would have been obvious over WO ’421
`considering the ’424 publication ......................................... 152
`Claims 4-10 would have been obvious over WO ’421
`considering the ’424 publication ......................................... 152
`Ground 4: Claims 1-10 of the ’462 Patent Would Have
`Been Obvious Over WO537 Considering Lovshin ............... 152
`a.
`Claim 1 would have been obvious over WO537 considering
`Lovshin .......................................................................... 153
`Claims 2 and 3 would have been obvious over WO537
`considering Lovshin ......................................................... 154
`Claims 4-10 would have been obvious over WO537
`considering Lovshin ......................................................... 155
`
`b.
`
`c.
`
`b.
`
`c.
`
`-4-
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`3.
`
`4.
`
`MPI EXHIBIT 1301 PAGE 4
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`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`b.
`
`c.
`
`
`
`5.
`
`Ground 5: Claims 1-10 of the ’462 Patent Would Have
`Been Obvious Over NCT657 and NCT773 ........................... 155
`a.
`Claim 1 would have been obvious over NCT657 and
`NCT773 ......................................................................... 156
`Claim 2 and 3 would have been obvious over NCT657 and
`NCT773 ......................................................................... 161
`Claims 4-10 would have been obvious over NCT657,
`NCT773, and the ’424 publication ...................................... 161
`IX. CONCLUSION ........................................................................................... 162
`
`
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`-5-
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`MPI EXHIBIT 1301 PAGE 5
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`

`

`
`
`TABLE OF ABBREVIATIONS
`
`
`Full Name of Cited Reference
`U.S. Patent App. Pub. No. US2007/0010424
`
`U.S. Patent No. 10,335,462
`
`Arrowsmith, J., Phase II failures: 2008–2010, Nature Reviews, Drug
`Discovery, Vol. 10 (May 2011)
`Declaration of John Bantle, MD
`
`Transcript of December 29, 2023 Deposition of John Bantle, M.D.
`
`Bhansali et al., Historical Overview of Incretin Based Therapies, 58
`SUPPL. TO JAPI 10 (2010)
`Blüher, M. et al., Dose-response effects on HbA1c and bodyweight
`reduction of survodutide, a dual glucagon/GLP-1 receptor agonist,
`compared with placebo and open-label semaglutide in people with type
`2 diabetes: a randomized clinical trial, Diabetologia (2023), available
`at https://link.springer.com/content/pdf/10.1007/s00125-023-06053-
`9.pdf
`Califf, Characteristics of Clinical Trials Registered in
`ClinicalTrials.gov, 2007-2010, 307 J. AM. MED. ASS’N 1838 (2012)
`Chatzigeorgiou et al., The Use of Animal Models in the Study of
`Diabetes Mellitus, 23 IN VIVO 245 (2009)
`NCT03144271, Dose Escalation of Single Subcutaneous Doses of NNC
`0113-0217 to Assess Safety, Tolerability, Pharmacokinetics and
`Pharmacodynamics in Healthy Male Subjects, available at
`https://clinicaltrials.gov/study/NCT03144271 (last visited December
`28, 2023)
`Drab, Incretin-Based Therapies for Type 2 Diabetes Mellitus: Current
`Status and Future Prospects, 30 PHARMACOTHERAPY 609 (2010)
`
`
`
`
`
`-6-
`
`
`
`Abbreviation
`’424
`publication
`(EX1016)
`’462 patent
`(EX1001)
`Arrowsmith
`(EX2006)
`Bantle Decl.
`(EX1003)
`Bantle Tr.
`(EX2018)
`Bhansali
`(EX1137)
`Blüher
`(EX2078)
`
`Califf
`(EX1279)
`Chatzigeorgiou
`(EX1290)
`Dose
`Escalation Trial
`(EX2070)
`
`Drab
`(EX1022)
`
`MPI EXHIBIT 1301 PAGE 6
`
`

`

`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`
`Full Name of Cited Reference
`Declaration of William J. Jusko, Ph.D., in Support of Petition for Inter
`Partes Review of U.S. Patent No. 10,335,462
`
`FDA Guidance for Industry, Exposure-Response Relationships - Study
`Design, Data, Analysis, and Regulatory Applications (Apr. 2003)
`
`International Conference on Harmonisation; Dose-Response
`Information to Support Drug Registration; Guideline; Availability, 59
`Fed. Reg. 55972 (Nov. 9, 1994)
`Transcript of January 5, 2024 Deposition of William J. Jusko, Ph.D.
`
`Kendall, Effects of Exenatide (Exendin-4) on Glycemic Control Over 30
`Weeks in Patients with Type 2 Diabetes Treated with Metformin and a
`Sulfonylurea, 28 DIABETES CARE 1083 (2005)
`Kim, K., et al., Differences in Drug Pharmacokinetics Between East
`Asians and Caucasians and the Role of Genetic Polymorphisms, J Clin
`Pharmacol, Vol.44, 1083-1105 (2004)
`Knight, A., Systematic Reviews of Animal Experiments Demonstrate
`Poor Contributions Toward Human Healthcare, Reviews on Recent
`Clinical Trials, Vol.3, Issue 2, 89-96 (2008)
`Knight, The Beginning of the End for Chimpanzee Experiments?, 3
`PHILOSOPHY, ETHICS, & HUMANITIES IN MED. 1 (2008)
`Knudsen, GLP-1 Derivatives as Novel Compounds for the Treatment of
`Type 2 Diabetes: Selection of NN2211 for Clinical Development, 26
`DRUGS OF THE FUTURE 677 (2001)
`Knudsen, Glucagon-like Peptide-1: The Basis of a New Class of
`Treatment for Type 2 Diabetes, 47 J. MED. CHEMISTRY 4128 (2004)
`Knudsen, Liraglutide: The Therapeutic Promise from Animal Models,
`64(suppl 167) INT J CLIN PRACT 4 (2010)
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes Mellitus, 5
`NATURE REVIEWS ENDOCRINOLOGY 262 (2009)
`
`
`
`- 7 -
`
`Abbreviation
`First
`Declaration or
`First Decl.
`(EX1005)
`FDA Exposure
`Response 2003
`(EX1048)
`ICH 1994
`(EX1049)
`
`Jusko Tr.
`(EX2019)
`Kendall
`(EX1287)
`
`Kim
`(EX2066)
`
`Knight
`(EX2005)
`
`Knight 2008
`(EX1280)
`Knudsen 2001
`(EX1031)
`
`Knudsen 2004
`(EX1032)
`Knudsen 2010b
`(EX1066)
`Lovshin
`(EX1012)
`
`MPI EXHIBIT 1301 PAGE 7
`
`

`

`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`
`Full Name of Cited Reference
`Lund, Emerging GLP-1Receptor Agonists, 16 EXPERT OPINION ON
`EMERGING DRUGS 607 (2011)
`Madsbad, An Overview of Once-Weekly Glucagon-Like Peptide-1
`Receptor Agonists - Available Efficacy and Safety Data and
`Perspectives for the Future, 13 DIABETES, OBESITY & METABOLISM 394
`(2011)
`Madsbad, S. et al., Improved Glycemic Control With No Weight
`Increase in Patients With Type 2 Diabetes After Once-Daily Treatment
`With the Long-Acting Glucagon-Like Peptide 1 Analog Liraglutide
`(NN2211), Diabetes Care, Vol.27, Issue 6, 1335-1342 (June 2004)
`Marre, GLP-1 Receptor Agonists Today, 93 DIABETES RSCH & CLIN.
`PRACTICE 317 (2011)
`Miller, M., et al., Low Viscosity Highly Concentrated Injectable
`Nonaqueous Suspensions of Lysozyme Microparticles, Langmuir,
`Author Manuscript (2011), PMC 2011 (Feb 17)
`Mueller, C., University of South Carolina Upstate, CHEM U109
`Chemistry of Living Things, 9.1:Solutions, available at
`https://chem.libretexts.org/Courses/University_of_South_Carolina_
`Upstate//USC_Upstate%3A_CHEM_U109__Chemistry_of_Living_
`Things_(Mueller) /09%3A_Solutions/9.1%3A_Solutions (last visited
`January 16, 2024)
`Clinical Trial No. NCT00696657
`
`Clinical Trial No. NCT00851773
`
`Novo Nordisk, “Annual Report 2010” (February 1, 2011)
`
`
`
`- 8 -
`
`Abbreviation
`Lund
`(EX1035)
`Madsbad
`(EX1052)
`
`Madsbad 2004
`(EX2075)
`
`Marre
`(EX1284)
`Miller
`(EX2004)
`
`Mueller
`(EX2077)
`
`NCT657
`(EX1013)
`NCT773
`(EX1014)
`Novo Nordisk,
`Annual Report
`2010
`(EX2065)
`
`MPI EXHIBIT 1301 PAGE 8
`
`

`

`
`
`
`Full Name of Cited Reference
`Novo Nordisk Annual Report 2011
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Novo Nordisk Earnings Call (Feb. 2, 2012)
`
`Novo Nordisk Form 6-K (May 1, 2009)
`
`Novo Nordisk Form 6-K (Feb. 2, 2011)
`
`Novo Nordisk 2010-2011 Pipeline
`
`Nordqvist, C., Experimental Diabetes Drug Taspoglutide Late-Stage
`Trials Suspended, available at
`https://www.medicalnewstoday.com/articles/200893#1 (September 13,
`2010)
`Ozempic® Prescribing Information (September 2023)
`
`Synapse, Pegylated GLP-1 analogue (LY2428757) – (Eli Lilly & Co.),
`available at
`https://synapse.patsnap.com/drug/482a547adeba4170ab23efa225fb966d
`(last updated December 27, 2023)
`
`
`
`- 9 -
`
`Abbreviation
`Novo Nordisk
`Annual Report
`2011
`(EX1130)
`Novo Nordisk
`Earnings Call
`(Feb. 2, 2012)
`(EX1285)
`Novo Nordisk
`Form 6-K (May
`1, 2009)
`(EX1282)
`Novo Nordisk
`SEC Filing
`(2011)
`(EX1131)
`Novo Nordisk
`Pipeline
`(EX1283)
`Norqvist
`(EX2061)
`
`Ozempic®
`Prescribing
`Label
`(EX2069)
`Pegylated
`GLP-1
`Analogue
`(LY2428757)
`EX2064
`
`MPI EXHIBIT 1301 PAGE 9
`
`

`

`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`
`Full Name of Cited Reference
`Rees, Animal Models of Diabetes Mellitus, 22 DIABET. MED. 359
`(2005)
`Evaluation and Licensing Division, Pharmaceutical and Food Safety
`Bureau, Ministry of Health, Labour and Welfare, Report on the
`Deliberation Results, available at
`https://www.pmda.go.jp/files/000153180.pdf (December 3, 2009)
`Declaration of Julio Rosenstock, M.D.
`
`Rosenstock, Early Diabetic Nephropathy: Assessment and Potential
`Therapeutic Interventions, 9 DIABETES CARE 529 (1986)
`
`Rosenstock, J., et al., Potential of Albiglutide, a Long-Acting GLP-1
`Receptor Agonist, in Type 2 Diabetes, Diabetes Care, Vol.32, Issue 10,
`1880-1886 (October 2009)
`Rosenstock, J., et al., The Fate of Taspoglutide, a Weekly GLP-1
`Receptor Agonist, Versus Twice-Daily Exenatide for Type 2 Diabetes,
`Diabetes Care, Vol.36, 498-504 (March 2013)
`Seino, Dose-Dependent Improvement in Glycemia with Once-Daily
`Liraglutide without Hypoglycemia or Weight Gain: A Double-Blind,
`Randomized, Controlled Trial in Japanese Patients with Type 2
`Diabetes, 81 DIABETES RSCH. & CLINICAL PRACTICE 161 (2008)
`Shargel, APPLIED BIOPHARMACEUTICS & PHARMACOKINETICS (5th ed.
`2005)
`Tamimi, Drug Development: From Concept to Marketing!, 113
`NEPHRON CLIN PRACT C125 (2009)
`
`
`
`- 10 -
`
`Abbreviation
`Rees
`(EX1289)
`Report on the
`Deliberation
`Results
`(EX2067)
`Rosenstock
`Declaration or
`Rosenstock
`Decl.
`(EX2010)
`Rosenstock
`1986
`(EX1291)
`Rosenstock
`2009
`(EX2062)
`Rosenstock
`2013
`(EX2060)
`Seino
`(EX1038)
`
`Shargel
`(EX1045)
`Tamimi
`(EX1047)
`
`MPI EXHIBIT 1301 PAGE 10
`
`

`

`Abbreviation
`Tanzeum®
`(albiglutide) –
`Drug
`Discontinuation
`EX2063
`Victoza label
`(EX1039)
`Victoza®
`Prescribing
`Information
`(January 2010)
`(EX2068)
`WO421
`(EX1011)
`WO537
`(EX1015)
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`
`Full Name of Cited Reference
`OPTUMRx, Tanzeum® (albiglutide) – Drug Discontinuation, available
`at https://professionals.optumrx.com/content/dam/optum3/professional-
`optumrx/news/rxnews/drug-recalls-
`shortages/drugwithdrawal_tanzeum_2017-0801.pdf (2017)
`
`Victoza, PHYSICIANS’ DESK REFERENCE (65th ed. 2010)
`
`Victoza® Prescribing Information (January 2010)
`
`International Patent App. Pub. No. WO 2011/138421
`
`International Patent App. Pub. No. WO 2006/097537
`
`
`
`- 11 -
`
`MPI EXHIBIT 1301 PAGE 11
`
`

`

`
`
`
`1.
`
`I am the same William J. Jusko, Ph.D. who previously submitted a
`
`declaration (“First Declaration” or “First Decl.,” EX1005) in this proceeding dated
`
`March 15, 2023 on behalf of Petitioner Mylan Pharmaceuticals Inc. (“Mylan” or
`
`“Petitioner”) in support of Mylan’s petition for inter partes review (“IPR”) of U.S.
`
`Patent No. 10,335,462 (“’462 patent,” EX1001). I understand that the Patent Trial
`
`and Appeal Board (“Board”) instituted IPR of the ’462 patent. Paper No. 10. I submit
`
`this declaration on behalf of Petitioner in support of Petitioner’s Reply. In particular,
`
`I respond to opinions expressed in the expert declaration of Julio Rosenstock, M.D.
`
`(“Rosenstock Declaration” or “Rosenstock Decl.,” EX2010) dated January 17, 2024,
`
`which was submitted in support of Patent Owner Novo Nordisk A/S’s (“Novo
`
`Nordisk” or “Patent Owner”) Response to the Petition.
`
`2.
`
`3.
`
`A copy of my curriculum vitae was submitted as EX1006.
`
`In providing my opinions in this declaration, in addition to my
`
`experience, education, and training, and the materials identified in Exhibit A to my
`
`First Declaration (EX1005), I have also considered the materials cited in the
`
`Rosenstock Declaration (EX2010), the materials identified in Exhibit A attached to
`
`this declaration, as well as any materials cited herein not otherwise identified in
`
`Exhibit A.
`
`4.
`
`I reaffirm that my scope of work and compensation has not changed
`
`since I submitted my First Declaration in this proceeding. I have been retained by
`
`
`
`
`
`-12-
`
`
`
`MPI EXHIBIT 1301 PAGE 12
`
`

`

`
`
`
`Mylan as a technical expert in this matter to provide various opinions regarding the
`
`
`
`’462 patent. EX1001. I receive my standard consulting rate of $800 per hour for my
`
`services. No part of my compensation is dependent upon my opinions given or the
`
`outcome of this proceeding.
`
`I.
`
`SUMMARY OF OPINIONS
`For the reasons stated in my First Declaration and in this declaration, I
`5.
`
`conclude that International Patent Application Publication No. WO 2011/138421
`
`(“WO421”), which was published on November 10, 2011, anticipates claims 1-3 of
`
`the ’462 patent (Ground 1).
`
`6.
`
`For the reasons stated in my First Declaration and in this declaration, I
`
`conclude that a review article titled “Incretin-Based Therapies for Type 2 Diabetes
`
`Mellitus” (“Lovshin”) authored by Julie A. Lovshin and Daniel J. Drucker, which
`
`was published in May 2009, anticipates claims 1-3 of the ’462 patent (Ground 2).
`
`7.
`
`For the reasons stated in my First Declaration and in this declaration, I
`
`conclude that claims 1-10 of the ’462 patent would have been obvious over WO421
`
`considering U.S. Patent Application Publication No. 2007/0010424 A1 (“’424
`
`Publication”) (Ground 3). I understand that Dr. Dalby offered an opinion that claims
`
`4-10 would have been obvious over WO421 considering the ’424 Publication, and I
`
`defer to his opinion for claims 4-10.
`
`
`
`- 13 -
`
`MPI EXHIBIT 1301 PAGE 13
`
`

`

`
`
`
`
`8.
`
`For the reasons stated in my First Declaration and in this declaration, I
`
`
`
`conclude that claims 1-10 of the ’462 patent would have been obvious over
`
`International Patent Application Publication No. WO 2006/097537 A2 (“WO537”)
`
`considering Lovshin (Ground 4). I understand that Dr. Dalby offered an opinion that
`
`claims 4-10 would have been obvious over WO537 considering Lovshin, and I defer
`
`to his opinion for claims 4-10.
`
`9.
`
`For the reasons stated in my First Declaration and in this declaration, I
`
`conclude that claims 1-10 of the ’462 patent would have been obvious over Clinical
`
`Trial No. NCT00696657 (“NCT657”), Clinical Trial No. NCT00851773
`
`(“NCT773”), and the ’424 Publication (Ground 5). I understand that Dr. Dalby
`
`offered an opinion that claims 4-10 would have been obvious over NCT657,
`
`NCT773, and the ’424 Publication, and I defer to his opinion for claims 4-10.
`
`10.
`
`I understand that Patent Owner Novo Nordisk has asserted that
`
`evidence of secondary considerations, including purported commercial success,
`
`unexpected results, long-felt need, industry praise, and skepticism, overcomes any
`
`showing of a prima facie case of obviousness for Grounds 3-5. I have reviewed the
`
`following declarations of Novo Nordisk’s experts in support of purported secondary
`
`considerations of nonobviousness:
`
`• George Bakris, M.D. regarding purported unexpected results related to
`kidney protective effects (EX2011);
`
`
`
`- 14 -
`
`MPI EXHIBIT 1301 PAGE 14
`
`

`

`
`
`
`
`
`
`• Robin S. Goland, M.D. regarding purported unexpected results, long
`felt but unmet need, industry praise, and skepticism (EX2054);
`
`• Michael Blaha, M.D. M.P.H. regarding purported unexpected results
`related to cardiovascular benefits (EX2055); and
`
`• Christopher A. Vellturo, Ph.D. regarding purported commercial
`success of Ozempic® (EX2300).
`I have also reviewed the following reply declarations of Petitioner
`
`11.
`
`Mylan’s experts:
`
`• Steven G. Coca, D.O., M.S. responding to Dr. Bakris (EX1306);
`
`• Allen Spiegel, M.D. responding to Dr. Goland (EX1302),
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`• Arthur Z. Schwartzbard, M.D., F.A.C.C. responding to Dr. Blaha
`(EX1304); and
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`• DeForest McDuff, Ph.D. responding to Dr. Vellturo (EX1308).
` After considering Novo Nordisk’s experts’ declarations regarding
`12.
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`secondary considerations of nonobviousness and Mylan’s experts’ reply
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`declarations, it remains my opinion that the claims of the ’462 patent would have
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`been obvious under each of Grounds 3-5.
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`II. LEGAL STANDARDS
`I continue to rely on the legal standards outlined in my First
`13.
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`Declaration. EX1005 (First Decl.) ¶¶ 22-27.
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`14.
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`In particular, I understand that my opinions regarding unpatentability
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`are presented from the viewpoint of a person of ordinary skill in the art (“POSA” or
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`MPI EXHIBIT 1301 PAGE 15
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`“skilled artisan” 2) in the field of technology of the patent at the time of the invention.
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`
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`It is my understanding that Patent Owner has asserted that claims 1-3 of the ’462
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`patent are entitled to an earlier invention date of March 17, 2010 or May 28, 2010,
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`but no later than July 1, 2012 for claims 1-3 and July 1, 2012 as to claims 4-10.
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`EX2010 (Rosenstock Decl.) ¶ 22. My opinions for this proceeding would not change
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`regardless of which of these dates is adopted by the Board.
`
`15.
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`I have been informed that Mylan bears the burden of proving
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`unpatentability by a preponderance of the evidence. I am informed that this
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`“preponderance-of-the-evidence” standard means that the Patent Trial and Appeal
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`Board must find it more likely than not that the claims are unpatentable.
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`16.
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`I understand that for a patent claim to be unpatentable as anticipated, a
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`prior art reference must disclose each element of the claim expressly and/or
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`inherently as arranged in the claim. I have been further informed that a reference can
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`anticipate a claim, even without expressly arranging or combining the components
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`as claimed, so long as a POSA would at once envisage the claimed arrangement or
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`combination upon reviewing the prior art reference.
`
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`2 Dr. Rosenstock uses the term “POSITA” to refer to the person of ordinary skill in
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`the art.
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`MPI EXHIBIT 1301 PAGE 16
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`17.
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`It is my understanding for a claimed feature to be considered “critical,”
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`
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`such that it is not anticipated by a prior art disclosure, the question is whether that
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`difference is “critical to the operability of the claimed invention.” I understand that
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`the criticality question is not just whether the claimed feature creates any difference
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`relative to a broader prior art disclosure.
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`18. Counsel has informed me that the concept of patent obviousness
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`involves four factual inquiries: (1) the scope and content of the prior art; (2) the
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`differences between the claimed invention and the prior art; (3) the level of ordinary
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`skill in the art; and (4) secondary considerations of non-obviousness.
`
`19.
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`It is my understanding from counsel that when there is some recognized
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`reason to solve a problem, and there are a finite number of identified, predictable
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`and known solutions, a person of ordinary skill in the art has good reason to pursue
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`the known options within his or her technical grasp. If such an approach leads to the
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`expected success, it is likely not the product of innovation but of ordinary skill and
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`common sense. It is my understanding that any need or problem known in the field
`
`of endeavor at the time of invention or addressed by the patent can provide a reason
`
`for combining prior art elements to arrive at the claimed subject matter. I understand
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`the obviousness of an invention, rendering it unpatentable, does not require absolute
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`predictability of outcome but that all that is required is a reasonable expectation of
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`success.
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`MPI EXHIBIT 1301 PAGE 17
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`20.
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`I understand that the secondary considerations that can be used to
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`
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`determine the obviousness of claimed subject matter may include evidence of such
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`things as commercial success, unexpected results over the closest prior art, long-felt
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`but unsolved needs, skepticism, and industry praise.
`
`21.
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`I understand that commercial success is premised on the concept that if
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`a product is economically successful, it may provide objective evidence of
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`nonobviousness. I further understand that the commercial success of the product
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`must be attributable to the alleged novel features of the claimed invention. I
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`understand this to mean that, to support a finding of nonobviousness, any alleged
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`commercial success must be driven by and attributable to the purported merits of the
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`patented invention, and not by other factors unrelated to the allegedly novel features
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`of the claimed invention. In other words, there must be a causal correlation, or
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`“nexus,” between the unique merit of the claimed invention and the success of the
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`product. I also understand that if purported commercial success is due to an element
`
`in the prior art, no nexus exists. In essence, I understand that if the feature that creates
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`the purported success was known in the prior art, such success is not pertinent.
`
`22.
`
`I understand that for Novo Nordisk to establish unexpected results, it
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`must demonstrate that there is a difference between the results produced by the
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`claimed invention and those produced by the closest prior art, and that the results
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`would have been unexpected by a POSA considering the prior art at the time of the
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`
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`invention. I also understand that for unexpected results to be persuasive, the new and
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`
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`unexpected results produced by the claimed invention must be different in kind, and
`
`not merely in degree, from the results produced by the prior art. I understand that a
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`difference in kind can be the presence of a new property dissimilar to the known
`
`property from the prior art. I also understand that Patent Owner, relying on
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`unexpected results to rebut a case of obviousness, must compare the claimed
`
`invention to the closest prior art.
`
`23.
`
`I understand that evidence of long-felt yet unmet need in the industry
`
`for the product covered by the invention may support the invention was not obvious.
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`24.
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`I understand that for industry praise to weigh against obviousness, it
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`must be specifically directed at the claimed invention. However, when praise is
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`linked to claim elements already known in the prior art or is unconnected to the
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`elements, this secondary consideration is given little weight.
`
`III. PERSON OF ORDINARY SKILL IN THE ART
`I continue to believe that a person of ordinary skill in the art would have
`25.
`
`had (1) an M.D., a Pharm. D., or a Ph.D. in pharmacy, chemical engineering,
`
`bioengineering, chemistry, or related discipline; (2) at least two years of experience
`
`in protein or peptide therapeutic development and/or manufacturing or diabetes
`
`treatments; and (3) experience with the development, design, manufacture,
`
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`MPI EXHIBIT 1301 PAGE 19
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`formulation, or administration of therapeutic agents, and the literature concerning
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`
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`protein or peptide formulation and design, or diabetes treatments.
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`26. Alternatively, the POSA would be (1) a highly skilled scientist lacking
`
`an M.D., Pharm. D., or Ph.D., but would have (2) more than five years of experience
`
`in the area of protein or peptide therapeutic development and/or manufacturing or
`
`diabetes treatments; and/or (3) experience with the development, design,
`
`manufacture, formulation, or administration of therapeutic agents, and the literature
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`concerning protein or peptide formulation and design, or diabetes treatments.
`
`27. A POSA would have understood the prior art references referred to
`
`herein and would have the capability to draw inferences. It is understood that, to the
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`extent necessary, a POSA may collaborate with one or more other POSAs for one or
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`more aspects with which the other POSA may have expertise, experience, and/or
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`knowledge. Additionally, a POSA could have had a lower level of formal education
`
`than what I describe here if the person has a higher degree of experience.
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`28.
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`It is my understanding that the Board adopted the above proposed
`
`definition of a skilled artisan for purposes of their Institution Decision. Paper No. 10
`
`at 20-21.
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`29.
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`I understand that Dr. Rosenstock proposed that “a person of ordinary
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`skill in the art to which the ’462 patent pertains would have an M.D. or, alternatively,
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`a Ph.D. or equivalent degree in Pharmacology, Pharmaceutics, Biopharmaceutics,
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`MPI EXHIBIT 1301 PAGE 20
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`or a related field. The M.D. or Ph.D. would have 3-5 years of experience conducting
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`
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`clinical research in the field of diabetes treatments, including in the design of dosing
`
`regimens and dosage forms for type 2 diabetes treatments, or would have 3-5 years
`
`of research or industry experience relating to developing pharmaceutical
`
`formulations and/or dosing regimens. Alternatively, the individual would be a highly
`
`skilled scientist lacking a Ph.D. or M.D., but would have more than 5 years of
`
`experience conducting clinical research in the field of diabetes treatments. The
`
`person of ordinary skill would consult, as appropriate with others having specific
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`expertise in pharmaceutical development, formulation, and manufacturing.”
`
`EX2010 (Rosenstock Decl.) ¶ 23.
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`30. As shown by my qualifications provided in my CV and as explained in
`
`my First Declaration, I met the qualifications of a POSA for purposes of the ’462
`
`patent under either party’s definition. My opinions expressed here would not change
`
`regardless of which party’s POSA definition is adopted.
`
`IV. CLAIM CONSTRUCTION
`31. For the reasons stated in my First Declaration, it remains my opinion
`
`that the plain and ordinary meaning of the preamble of claim 1 of the ’462 patent,
`
`“[a] method of treating type 2 diabetes,” would have been understood by a skilled
`
`artisan to broadly encompass administration of semaglutide for the purpose of
`
`alleviating or reducing the symptoms and complications associated with type 2
`
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`MPI EXHIBIT 1301 PAGE 21
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`diabetes or otherwise managing the disease without requiring any specified
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`
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`treatment effect. EX1005 (First Decl.) ¶¶ 58-60.
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`32. This plain and ordinary meaning is supported by the specification of the
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`’462 patent, which confirms this meaning of the term “treating” and states:
`
`the term “treatment” or “treating” is intended to include the full
`spectrum of treatments for a given condition f