`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`MYLAN PHARMACEUTICALS INC., DR. REDDY’S LABORATORIES, INC.,
`and DR. REDDY’S LABORATORIES, LTD.
`Petitioner,
`v.
`NOVO NORDISK A/S,
`Patent Owner.
`
`IPR2023-007241
`Patent 10,335,462 B2
`
`Reply Declaration of Dr. John Bantle
`
`
`
`
`
`
`
`
`
`
`1 IPR2024-00009 (Dr. Reddy’s Laboratories) has been joined with this proceeding.
`
`
`
`MPI EXHIBIT 1300 PAGE 1
`
`

`

`TABLE OF CONTENTS
`
`
`I.
`Basis of Opinions and Materials Considered .................................................. 9
`Summary of Opinions ...................................................................................... 9
`II.
`III. Legal Standards .............................................................................................12
`IV. Person of Ordinary Skill in the Art ................................................................18
`V.
`The ’462 Patent and Its Claims......................................................................20
`A.
`The ’462 patent’s claims .....................................................................20
`B.
`Claim construction ..............................................................................24
`VI. Technical Background of the ’462 patent .....................................................25
`A. Asserted prior art .................................................................................26
`1.
`EX1011 (WO421) .....................................................................26
`2.
`EX1012 (Lovshin).....................................................................30
`3.
`EX1013 (NCT657) ....................................................................33
`4.
`EX1014 (NCT773) ....................................................................34
`5.
`EX1015 (WO537) .....................................................................35
`6.
`EX1016 (’424 Publication) .......................................................36
`Additional references in the art ...........................................................37
`1.
`EX2005 (Knight).......................................................................37
`2.
`EX2006 (Arrowsmith) ..............................................................44
`3.
`EX2065 (Novo Nordisk Annual report (2010)) ........................48
`4.
`EX2067 (Deliberation Results) .................................................53
`5.
`EX2066 (Kim) ...........................................................................55
`6.
`EX2062 (Rosenstock (2009)) ...................................................56
`7.
`EX2075 (Madsbad (2004)) .......................................................58
`8.
`EX2061 (Nordqvist) ..................................................................61
`Other references ..................................................................................64
`1.
`EX1035 (Lund) .........................................................................64
`2.
`EX1038 (Seino).........................................................................68
`3.
`EX1047 (Tamimi) .....................................................................69
`D. Allegedly failed and withdrawn GLP-1 Receptor Agonists ...............70
`
`B.
`
`C.
`
`
`
`2
`
`MPI EXHIBIT 1300 PAGE 2
`
`

`

`2.
`
`2.
`
`TABLE OF CONTENTS
`VII. Unpatentability of the Claims of the ’462 Patent ..........................................78
`A. General deficiencies in the Rosenstock Declaration’s opinions .........78
`1.
`The Rosenstock Declaration failed to apply the correct claim
`construction ...............................................................................78
`The Rosenstock Declaration incorrectly asserts that semaglutide
`dosing could be understood in multiples of micrograms ..........82
`The Rosenstock Declaration did not rebut Ground 1: WO421
`Anticipated Claims 1–3 .......................................................................87
`1. WO421 anticipated claim 1 ......................................................87
`2. WO421 anticipated claims 2-3 ................................................104
`The Rosenstock Declaration did not rebut Ground 2: Lovshin
`Anticipated Claims 1-3 ......................................................................106
`1.
`Lovshin anticipated claim 1 ....................................................106
`2.
`Lovshin anticipated claims 2-3 ...............................................114
`The Rosenstock Declaration did not rebut the Conclusion that there
`was a Motivation to Combine the Prior Art with a Reasonable
`Expectation of Success ......................................................................116
`1.
`A POSA would have been motivated to combine the prior art to
`reach the claimed method of treatment ...................................116
`A POSA would have had a reasonable expectation of success
`achieving the claimed method ................................................127
`The Rosenstock Declaration did not rebut Ground 3: Claims 1–10 of
`the ’462 patent would have been obvious over WO421 alone or in
`view of the ’424 publication ..............................................................160
`The Rosenstock Declaration did not rebut Ground 4: Claims 1–10 of
`the ’462 patent would have been obvious over WO537 in view of
`Lovshin ..............................................................................................163
`The Rosenstock Declaration did not rebut Ground 5: Claims 1–10 of
`the ’462 patent would have been obvious over NCT657 in view of
`NCT773 and further in view of the ’424 publication ........................169
`VIII. Reservation of Rights ..................................................................................178
`
`
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`G.
`
`
`
`3
`
`MPI EXHIBIT 1300 PAGE 3
`
`

`

`TABLE OF ABBREVIATIONS
`
`Full Name of Cited Reference
`U.S. PAT. APPLICATION PUBL’N NO. US2007/0010424
`
`U.S. PATENT NO. 10,335,462
`
`Amori et al., Efficacy and Safety of Incretin Therapy in
`Type 2 Diabetes, 298 J. AM. MED. ASS’N 194 (2007)
`Astrup et al., Effects of Liraglutide in the Treatment of
`Obesity: A Randomised, Double-Blind, Placebo-
`Controlled Study, 374 LANCET 1606 (2009)
`Bhansali, Historical Overview of Incretin Based
`Therapies, 58 J. ASSOC. OF PHYSICIANS OF INDIA 10 (2010)
`Highlights of Prescribing Information: Byetta, Revised:
`10/2009
`Califf et al., 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)
`Drab, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus: Current Status and Future Prospects, 30
`PHARMACOTHERAPY 609 (2010)
`Drucker, The Incretin System: Glucagon-Like Peptide-1
`Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors
`in Type 2 Diabetes, 368 LANCET 1696 (2006)
`Transcript of the Novo Nordisk Earnings Call of February
`2, 2012.
`
`NOVO NORDISK A/S FORM 6-K REPORT OF FOREIGN
`PRIVATE ISSUER (Feb. 2, 2011)
`
`Abbreviation
`’424 publication
`(EX1016)
`’462 patent
`(EX1001)
`Amori
`(EX1132)
`Astrup
`(EX1096)
`
`Bhansali
`(EX1137)
`Byetta label
`(EX1021)
`Califf
`(EX1279)
`
`Chatzigeorgiou
`(EX1290)
`Drab
`(EX1022)
`
`Drucker 2006
`(EX1024)
`
`Feb. 2, 2012 Novo
`Nordisk Earnings Call
`(EX1285)
`Form 6-K
`(EX1131)
`
`4
`
`
`
`
`
`MPI EXHIBIT 1300 PAGE 4
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`Holst, Glucagon-Like Peptide 1 and Inhibitors of
`Dipeptidyl Peptidase IV in the Treatment of Type 2
`Diabetes Mellitus, 4 CURRENT OP. IN PHARMACOLOGY 589
`(2004)
`Jimenez-Solem, Dulaglutide, a Long-Acting GLP-1
`Analog Fused with an Fc Antibody Fragment for the
`Potential Treatment of Type 2 Diabetes, 12 CURRENT OP.
`IN MOLECULAR THERAPEUTICS 790 (2010)
`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, Effects of Once-Weekly Dosing of a Long-Acting
`Release Formulation of Exenatide on Glucose Control and
`Body Weight in Subjects with Type 2 Diabetes, 30
`DIABETES CARE 1487 (2007)
`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, a GLP-1 Analogue to Treat
`Diabetes in ANALOGUE-BASED DRUG DISCOVERY II
`(Fischer & Ganellin eds. 2010)
`Knudsen, Liraglutide: The Therapeutic Promise from
`Animal Models, 64(suppl 167) INT’L J. CLINICAL PRACTICE
`4 (2010)
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REV. ENDOCRINOLOGY 262 (2009)
`
`Abbreviation
`Holst 2004
`(EX1028)
`
`Jimenez-Solem
`(EX1029)
`
`Kendall
`(EX1287)
`
`Kim
`(EX1030)
`
`Knight
`(EX1280)
`
`Knudsen 2001
`(EX1031)
`
`Knudsen 2004
`(EX1032)
`
`Knudsen 2010
`(EX1033)
`
`Knudsen 2010b
`(EX1066)
`
`Lovshin
`(EX1012)
`
`
`
`5
`
`MPI EXHIBIT 1300 PAGE 5
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`Lund, Emerging GLP-1 Receptor Agonists, 16 EXPERT OP.
`ON EMERGING DRUGS 607 (2011)
`Marre, GLP-1 Receptor Agonists Today, 93 DIABETES
`RSCH. & CLINICAL PRAC. 317 (2011)
`Clinical Trial No. NCT00696657
`
`Clinical Trial No. NCT00851773
`
`Nielsen, Pharmacology of Exenatide (Synthetic Exendin-
`4): A Potential Therapeutic for Improved Glycemic
`Control of Type 2 Diabetes, 117 REGUL. PEPTIDES 77
`(2004)
`Novo Nordisk, ANNUAL REPORT 2010 (Feb. 1, 2011)
`
`Novo Nordisk Pipeline – Semaglutide (2010-2011)
`http://novonordisk.com:80/science/pipeline
`/rd_pipeline.asp?showid=7 (Internet Archive captures)
`Rees, Animal Models of Diabetes Mellitus, 22 DIABETIC
`MED. 359 (2005)
`Rosenstock, Early Diabetic Nephropathy: Assessment and
`Potential Therapeutic Interventions, 9 DIABETES CARE 529
`(1986)
`Rosenstock et al., Potential of Albiglutide, a Long-Acting
`GLP-1 Receptor Agonist, in Type 2 Diabetes, 32 DIABETES
`CARE 1880 (2009)
`Rosenstock et al., The Fate of Taspoglutide, a Weekly
`GLP-1 Receptor Agonist, Versus Twice-Daily Exenatide
`for Type 2 Diabetes, 36 DIABETES CARE 498 (2013)
`Transcript of the May 15, 2024 Deposition of Julio
`Rosenstock, M.D.
`
`Abbreviation
`Lund
`(EX1035)
`Marre
`(EX1284)
`NCT657
`(EX1013)
`NCT773
`(EX1014)
`Nielsen
`(EX1037)
`
`Novo Nordisk Annual
`report (2010)
`(EX2065)
`Novo Pipeline
`(EX1283)
`
`Rees
`(EX1289)
`Rosenstock 1986
`(EX1291)
`
`Rosenstock 2009
`(EX2062)
`
`Rosenstock 2013
`(EX2060)
`
`Rosenstock Dep.
`(EX1313)
`
`
`
`6
`
`MPI EXHIBIT 1300 PAGE 6
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`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)
`Tamimi, Drug Development: From Concept to Marketing!,
`113 NEPHRON CLINICAL PRAC. c125 (2009)
`Victoza, PHYSICIANS’ DESK REFERENCE (65th ed. 2010)
`
`INT’L PAT. APPLICATION PUBL’N NO. WO 2011/058193
`
`INT’L PAT. APPLICATION PUBL’N NO. WO 2011/073328
`
`INT’L PAT. APPLICATION PUBL’N NO. WO 2011/138421
`
`INT’L PAT. APPLICATION PUBL’N NO. WO 2006/097537
`
`Abbreviation
`Seino
`(EX1038)
`
`Tamimi
`(EX1047)
`Victoza label
`(EX1039)
`WO193
`(EX1060)
`WO328
`(EX1057)
`WO421
`(EX1011)
`WO537
`(EX1015)
`
`
`
`
`
`7
`
`MPI EXHIBIT 1300 PAGE 7
`
`

`

`
`
`1.
`
`I, John Bantle, M.D., have been retained by Mylan Pharmaceuticals Inc.
`
`(“Mylan”) in the inter partes review identified in the caption above. I submitted an
`
`expert declaration in this matter, dated March 14, 2023, which was designated
`
`Exhibit 1003 (“First Declaration”). In that declaration, I showed that claims 1-10 of
`
`U.S. Patent No. 10,335,462 to Jensen (“the ’462 patent”) (EX1001) were either
`
`anticipated by the prior art or would have been obvious to a person of ordinary skill
`
`in the art at their priority date. See generally EX1003.
`
`2. My qualifications, previous testimony, and compensation are provided
`
`in my First Declaration.
`
`3.
`
`I submit this reply expert declaration to further support my opinions
`
`regarding the ’462 patent, and to reply to certain opinions set forth in the January
`
`17, 2024 Declaration of Julio Rosenstock, M.D. (“Rosenstock Decl.”), filed on
`
`behalf of the Patent Owner Novo Nordisk, which was designated Exhibit 2010 (or
`
`EX2010). To the extent I do not expressly address in this declaration a point made
`
`by Dr. Rosenstock, it does not mean that I agree with it.
`
`4.
`
`The scope of my work and my compensation remains the same since I
`
`submitted my First Declaration. I was retained as a technical expert to provide
`
`opinions related to the ’462 patent. My compensation does not depend upon the
`
`outcome of this proceeding or my opinions. I have no current affiliation with Novo
`
`Nordisk A/S or the named inventor of the ’462 patent.
`
`
`
`8
`
`MPI EXHIBIT 1300 PAGE 8
`
`

`

`
`
`I.
`
`BASIS OF OPINIONS AND MATERIALS CONSIDERED
`
`5.
`
`To reach the conclusions and opinions described in my declaration, I
`
`considered and relied upon the materials cited in my First Declaration (EX1003), the
`
`materials identified in Exhibit A to my First Declaration, the materials cited in the
`
`Rosenstock Declaration (EX2010), and any materials cited in this declaration and
`
`not otherwise identified in Exhibit A to this declaration. My conclusions and
`
`opinions are also based on my education, experience, knowledge, and training.
`
`II.
`
`SUMMARY OF OPINIONS
`
`6.
`
`Having reviewed the Rosenstock Declaration, and in view of the
`
`reasons stated here and in my First Declaration, I remain of the opinion that WO421
`
`anticipated claims 1-3 of the ’462 patent. See EX1003 Ground 1 (§IX.A).
`
`7.
`
`Having reviewed the Rosenstock Declaration, and in view of the
`
`reasons stated here and in my First Declaration, I remain of the opinion that Lovshin
`
`anticipated claims 1-3 of the ’462 patent. See EX1003 Ground 2 (§IX.B).
`
`8. My opinions focus on the treatment of diabetes as recited and claimed
`
`in claims 1–3 of the ’462 patent. Having reviewed the Rosenstock Declaration, and
`
`in view of the reasons stated here and in my First Declaration, and in view of Dr.
`
`Dalby’s opinion that claims 4–10 of the ’462 patent would have been obvious over
`
`WO421 in view of the ’424 publication, I remain of the opinion that claims 1-10 of
`
`
`
`9
`
`MPI EXHIBIT 1300 PAGE 9
`
`

`

`
`
`the ’462 patent would have been obvious over WO421 in view of the ’424
`
`publication. See EX1003 Ground 3 (§IX.C).
`
`9. My opinions focus on the treatment of diabetes as recited and claimed
`
`in claims 1–3 of the ’462 patent. Having reviewed the Rosenstock Declaration, and
`
`in view of the reasons stated here and in my First Declaration, and in view of Dr.
`
`Dalby’s opinion that claims 4–10 of the ’462 patent would have been obvious over
`
`WO537 in view of Lovshin, I remain of the opinion that claims 1-10 of the ’462
`
`patent would have been obvious over WO537 in view of Lovshin. See EX1003
`
`Ground 4 (§IX.D).
`
`10. My opinions focus on the treatment of diabetes as recited and claimed
`
`in claims 1–3 of the ’462 patent. Having reviewed the Rosenstock Declaration, and
`
`in view of the reasons stated here and in my First Declaration, and in view of Dr.
`
`Dalby’s opinion that claims 4–10 of the ’462 patent would have been obvious over
`
`NCT657, NCT773, and the ’424 publication, I remain of the opinion that claims 1-
`
`10 of the ’462 patent would have been obvious over NCT657, NCT773, and the ’424
`
`publication. See EX1003 Ground 5 (§IX.E).2
`
`
`2 The details of the protocol described in EX1014 (NCT773) vary slightly by the
`
`date of the disclosure. One version of the disclosure, which states, “Last Updated on
`
`July 15, 2010,” includes an experimental arm in which the highest dose amount is
`
`
`
`10
`
`MPI EXHIBIT 1300 PAGE 10
`
`

`

`
`
`11.
`
`I understand that Patent Owner Novo Nordisk asserted that certain
`
`evidence, including the supposed commercial success of Ozempic®, and alleged
`
`unexpected results, long-felt need, industry praise, and skepticism of the claimed
`
`inventions, provides secondary considerations (or what Dr. Rosenstock terms
`
`“objective indicia,” EX2010 (Rosenstock Decl.) ¶ 35) of nonobviousness sufficient
`
`to overcome any prima facie case of obviousness established for Grounds 3-5,
`
`described above. I reviewed the following expert declarations related to Novo
`
`Nordisk’s alleged secondary considerations of nonobviousness:
`
`a. In support of Novo Nordisk’s position responding to Mylan’s IPR petition:
`
`
`“1.2 mg once weekly for 6 weeks.” See EX1014 (NCT773) at 7. A second version
`
`of the disclosure, which states, “Last Updated: August 26, 2009,” includes an
`
`experimental arm in which the highest dose amount is “to be determined based on
`
`safety and tolerability of previous dose steps,” and an arm in which the highest dose
`
`amount is “1.6 mg once weekly for 6 weeks.” See EX1014 (NCT773) at 11. My
`
`opinion that the claims of the ’462 patent are unpatentable over a ground that
`
`includes NCT773 do not require the July 15, 2010 version of the disclosure of
`
`NCT773: this disclosure just confirms my opinion that the claims are unpatentable
`
`even in view of the August 26, 2009 version of the disclosure of NCT773.
`
`
`
`11
`
`MPI EXHIBIT 1300 PAGE 11
`
`

`

`
`
`i. Dr. George Bakris regarding purported unexpected results related to
`
`kidney protective effects (EX2011);
`
`ii. Dr. Robin Goland, M.D. regarding purported unexpected results,
`
`long felt but unmet need, industry praise, and skepticism (EX2054);
`
`iii. Dr. Michael Blaha regarding purported unexpected results related to
`
`cardiovascular benefits (EX2055); and
`
`iv. Dr. Christopher Vellturo regarding purported commercial success of
`
`Ozempic® (EX2300).
`
`b. In support of Mylan’s position in reply:
`
`i. Dr. Steven Coca (EX1306), who responds to Dr. Bakris;
`
`ii. Dr. Allen Spiegel (EX1302), who responds to Dr. Goland;
`
`iii. Dr. Arthur Schwartzbard (EX1304), who responds to Dr. Blaha; and
`
`iv. Dr. DeForest McDuff (EX1308), who responds to Dr. Vellturo.
`
`12. After considering these declarations, it remains my opinion that claims
`
`1-10 of the ’462 patent are unpatentable because they would have been obvious over
`
`the prior art for the reasons set forth in each of Grounds 3-5.
`
`III. LEGAL STANDARDS
`
`13.
`
`In addition to the legal standards set forth in my First Declaration, see,
`
`e.g., EX1003 (First Decl.) §III, I have been informed of the following additional
`
`legal principles.
`
`
`
`12
`
`MPI EXHIBIT 1300 PAGE 12
`
`

`

`
`
`14. As I stated in my First Declaration, it is my understanding that
`
`obviousness is determined from the viewpoint of a person of ordinary skill in the art
`
`(“POSA”) in the field of technology of the patent as of the patent’s priority date.3 In
`
`addition, as I noted in my First Declaration, 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.
`
`15.
`
`I am told that the concept of patent obviousness involves four factual
`
`inquiries: (1) the scope and content of the prior art; (2) the differences between the
`
`claimed invention and the prior art; (3) the level of ordinary skill in the art; and (4)
`
`secondary considerations of nonobviousness.
`
`16.
`
`I understand that asserted secondary considerations of nonobviousness
`
`may include evidence of such things as commercial success, unexpected results over
`
`
`3 Dr. Rosenstock asserts that the invention or priority date for claims 1-3 of the ’462
`
`patent is “March 17, 2010, or at least May 28, 2010 … but in any event no later than
`
`July 1, 2012,” and for claims 4-10 is July 1, 2012. EX2010 (Rosenstock Decl.) ¶ 22.
`
`My ultimate opinions that the claims of the ’462 patent were anticipated by or would
`
`have been obvious over the prior art would be the same regardless of which date the
`
`Board adopts.
`
`
`
`13
`
`MPI EXHIBIT 1300 PAGE 13
`
`

`

`
`
`the closest prior art, long-felt but unmet needs, skepticism in the art, and industry
`
`praise.
`
`17.
`
`I understand that the idea of commercial success, as it relates to
`
`nonobviousness, is premised on the idea that if a product is economically successful,
`
`that success may be evidence of nonobviousness. I also understand that for
`
`commercial success of a product to be evidence of nonobviousness, that success
`
`must be attributable to the alleged novel features of the claimed invention. I
`
`understand this to mean, in other words, that any alleged commercial success must
`
`be driven by and attributable to the purported merits of the patented invention, and
`
`not by other factors unrelated to the allegedly novel features of the claimed
`
`invention. In short, there must be a causal correlation, or “nexus,” between the
`
`unique merit of the claimed invention and the success of the product. I also
`
`understand that if any alleged commercial success is due to an element that exists in
`
`the prior art, there is no nexus; meaning that if the feature that creates the purported
`
`success was known in the prior art, that alleged success is not pertinent to
`
`nonobviousness of the claimed invention.
`
`18.
`
`I understand that unexpected results due to a claimed invention may
`
`also be evidence of nonobviousness. I understand that for a Patent Owner to establish
`
`unexpected results, it must demonstrate that there is a difference between the results
`
`produced by the claimed invention and those produced by the closest prior art, and
`
`
`
`14
`
`MPI EXHIBIT 1300 PAGE 14
`
`

`

`
`
`that the results would have been unexpected by a POSA considering the prior art at
`
`the time of the invention. I also understand that for alleged unexpected results to be
`
`persuasive evidence of nonobviousness, those 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 difference in kind can be the
`
`presence of a new property dissimilar to a known property in the prior art. I also
`
`understand that a Patent Owner, when relying on unexpected results to rebut a case
`
`of obviousness, must compare the claimed invention to the closest prior art, as noted
`
`above.
`
`19.
`
`I understand that evidence of long-felt but unmet need in the industry
`
`for the product covered by the invention may also be evidence of nonobviousness.
`
`20.
`
`I understand that evidence of industry praise for a claimed invention
`
`may also be evidence of its nonobviousness. I understand that for industry praise to
`
`weigh against obviousness, that praise must be specifically directed at the claimed
`
`invention. However, I understand that little weight is given to this evidence when
`
`any alleged praise is linked to claim elements already known in the prior art or is
`
`unconnected to the elements of the claimed invention.
`
`21.
`
`I understand that when there is some recognized reason to solve a
`
`problem, and there are a finite number of identified, predictable and known
`
`solutions, a person of ordinary skill in the art has good reason to pursue the known
`
`
`
`15
`
`MPI EXHIBIT 1300 PAGE 15
`
`

`

`
`
`options within his or her technical grasp. If such an approach leads to the expected
`
`success, it is likely not the product of innovation but of ordinary skill and common
`
`sense. I understand 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 that only a
`
`reasonable expectation of success is necessary to show obviousness.
`
`22.
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`I understand that the obviousness of an invention, rendering it
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`unpatentable, does not require absolute predictability of outcome; all that is required
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`is a reasonable expectation of success.
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`23.
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`I further understand that the motivation to combine prior art references
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`can come from a POSA’s background knowledge and common sense. It is my
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`understanding that a POSA is not treated as an automaton, but rather is ascribed an
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`ordinary level of creativity. And a POSA considers prior art not just for what it
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`expressly teaches, but what it fairly suggests. Further, it is my understanding that a
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`POSA’s common sense informs them that known prior art can be extended beyond
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`its primary teaching and can be combined with other prior art.
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`24.
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`It is also my understanding that when reviewing clinical trials for
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`obviousness determinations, efficacy, pharmacokinetic, and pharmacodynamic data
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`are not necessarily required. Rather a POSA when viewing clinical trials would
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`consider their limits and understand what they fairly teach and don’t teach.
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`
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`25.
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`I understand that even a considerable amount of experimentation is
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`permissible, if it is merely routine. In other words, the length, expense, and difficulty
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`of the techniques used are not dispositive since many techniques that require
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`extensive time, money, and effort to carry out may nevertheless be routine to one of
`
`ordinary skill in the art. Instead, an invention may be obvious if one skilled in the art
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`would have had a reasonable expectation of success at the time the invention was
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`made, and merely had to verify that expectation.
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`26.
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`I further understand that where the general conditions of a claim are
`
`disclosed in the prior art, it is not inventive to discover the optimum or workable
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`ranges by routine experimentation. Related to this, I understand that a prima facie
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`case of obviousness exists when the only difference from the prior art is a difference
`
`in the range or value of a particular variable.
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`27.
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`It is my understanding that when combining prior art reference, an
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`invention is not nonobvious simply because other better combinations exist. Rather
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`the invention may still be obvious so long as the combination was a suitable option.
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`I understand that an obvious solution does not become nonobvious simply because
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`other solutions might also be obvious.
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`28.
`
`I understand that for a claimed feature to be considered “critical” to the
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`invention, such that it is not anticipated by a prior art disclosure, the question is
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`whether that difference is “critical to the operability of the claimed invention.” I
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`
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`understand that the question of whether a feature is critical is not just whether the
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`claimed feature creates any difference relative to a broader prior art disclosure.
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`29.
`
`I understand that once a patent challenger has established, through
`
`overlapping ranges, a prima facie case of anticipation of a claimed feature, the
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`burden of production falls upon the patentee to come forward with evidence that the
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`claimed feature is critical.
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`30.
`
`I understand that for a claimed feature to be considered “critical,” such
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`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 further
`
`understand that the question of whether a feature is critical is not simply whether the
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`claimed feature creates any difference relative to a broader prior art disclosure.
`
`31.
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`I understand that a person of ordinary skill in the art can expect that
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`compounds with common properties, such as significant structural and functional
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`similarity, are likely to share other related properties as well.
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`IV. PERSON OF ORDINARY SKILL IN THE ART
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`32.
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`I again apply the definition of a person of ordinary skill in the art
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`(“POSA”)4 set forth in my First Declaration (EX1003 ¶¶25-29): The subject matter
`
`of claims 1–10 of the ’462 patent falls within the medicinal chemical arts. A skilled
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`4 Dr. Rosenstock uses the acronym “POSITA.”
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`
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`artisan would have had (1) an M.D., a Pharm.D., or a Ph.D. in pharmacy, chemical
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`engineering, bioengineering, chemistry, or related discipline; (2) at least two years
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`of experience in protein or peptide therapeutic development and/or manufacturing
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`or diabetes treatments; and (3) experience with the development, design,
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`manufacture, formulation, or administration of therapeutic agents, and the literature
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`concerning protein or peptide formulation and design, or diabetes treatments.
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`33. Alternatively, the skilled artisan would be (1) a highly skilled scientist
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`lacking an M.D., a Pharm.D., or a Ph.D., but would have (2) more than five years of
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`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
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`literature concerning protein or peptide formulation and design, or diabetes
`
`treatments.
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`34. A skilled artisan would have understood the prior art references referred
`
`to herein and would have the capability to draw inferences. It is understood that, to
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`the extent necessary, a skilled artisan may collaborate with one or more other skilled
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`artisans for one or more aspects with which the other skilled artisan may have
`
`expertise, experience, and/or knowledge. Additionally, a skilled artisan could have
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`had a lower level of formal education than what I describe here if the person has a
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`higher degree of experience.
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`
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`35.
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`I understand that the Board adopted this definition of a POSA in its
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`Institution Decision, focusing on the first paragraph of the definition. See Paper 10
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`at 20.
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`36.
`
`I understand that Patent Owner’s expert, Dr. Rosenstock, in forming his
`
`opinions, set forth a POSA definition different from mine. EX2010 (Rosenstock
`
`Decl.) ¶ 23. My opinions would not be different if I applied Patent Owner and Dr.
`
`Rosenstock’s definition.
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`V. THE ’462 PATENT AND ITS CLAIMS
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`37. The ’462 patent is titled “Use of Long-Acting GLP-1 Peptides.”
`
`EX1001.
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`A. The ’462 patent’s claims
`
`38. The ’462 patent concludes with ten claims, set forth below.
`
`39. Claim 1 of the ’462 patent, the only independent claim, recites:
`
`1. A method for treating type 2 diabetes, comprising
`
`administering semaglutide once weekly in an amount of
`
`1.0 mg to a subject in need thereof.
`
`40. Dependent claims 2–10 of the ’462 patent depend from claim 1, directly
`
`or indirectly, and are provided here.
`
`41. Dependent claim 2 recites:
`
`
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`2. The method according to claim 1, wherein the
`semaglutide is administered by parenteral administration.
`42. Dependent claim 3 recites:
`
`3. The method according to claim 2, wherein the solution
`is administered by subcutaneous injection.
`43. Dependent claim 4 recites:
`
`4. The method according to claim 1, wherein the
`semaglutide is administered in the form of an isotonic
`aqueous solution comprising phosphate buffer at a pH in
`the range of 7.0-9.0.
`44. Dependent claim 5 recites:
`
`5. The method according to claim 4, wherein the solution
`further comprises propylene glycol and phenol.
`45. Dependent claim 6 recites:
`
`6. The method according to claim 4, wherein the pH is 7.4.
`46. Dependent claim 7 recites:
`
`7. The method according to claim 6, wherein the solution
`further comprises propylene glycol and phenol.
`47. Dependent claim 8 recites:
`
`8. The method according to claim 4, wherein the
`phosphate buffer is a sodium dihydrogen phosphate
`buffer.
`48. Dependent claim 9 recites:
`
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`
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`9. The method according to claim 1, wherein the
`semaglutide is administered by subcutaneous injection in
`the form of an isotonic aqueous solution comprising at a
`sodium dihydrogen phosphate buffer at a pH in the range
`of 7.0-9.0, and wherein the solution further comprises
`propylene glycol and phenol.
`49. Dependent claim 10 recites:
`
`10. The method according to claim 9, wherein the pH is
`7.4.
`In ¶ 54, Dr. Rosenstock quotes the ’462 patent as saying that “[t]he
`
`50.
`
`results (see e.g. FIG. 1) show[] that treatment with semaglutide 0.8 mg, 0.8 mg T
`
`[titrated in .04 mg weekly increments], or 1.6 mg T improved reduction of HbA1c
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`compared to treatment with [once-daily] liraglutide 1.2 mg or 1.8 mg….” EX2010
`
`(Rosenstock Decl.) ¶ 54 (quoting EX1001, 22:12-15) (emphasis omitted)
`
`(alter