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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.,
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`Petitioner,
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`v.
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`NOVO NORDISK A/S,
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`Patent Owner.
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`Case No. IPR2023-00723
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`Patent No. 8,129,343
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`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,129,343
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`TABLE OF CONTENTS
`
`
`Introduction ..................................................................................................... 1
`I.
`II. Mandatory Notices.......................................................................................... 2
`A.
`Real Parties-In-Interest ......................................................................... 2
`B.
`Related Matters ..................................................................................... 2
`C.
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) .............................. 4
`D.
`Service Information (37 C.F.R. § 42.8(b)(4)) ...................................... 4
`III. Requirements for Inter Partes Review ........................................................... 5
`A. Grounds for Standing ........................................................................... 5
`B.
`Identification of Challenge and Statement of Precise Relief
`Requested ............................................................................................. 5
`IV. Threshold Requirement for Inter Partes Review ........................................... 6
`V.
`Statement of Reasons for the Relief Requested ............................................. 6
`A.
`Summary of the Argument ................................................................... 6
`B.
`Level of Ordinary Skill in the Art ........................................................ 7
`C.
`The ’343 Patent .................................................................................... 9
`1.
`Disclosure ................................................................................... 9
`2.
`Priority Date ............................................................................. 10
`3.
`Claims ...................................................................................... 10
`4.
`Prosecution History .................................................................. 12
`Claim Construction (37 C.F.R. §§ 42.100(b), 42.104(b)(3)) ............. 13
`Scientific Background ........................................................................ 14
`1.
`Diabetes .................................................................................... 14
`2.
`GLP-1 ....................................................................................... 14
`3.
`Peptide Synthesis and Structure Screening .............................. 16
`Scope and Content of the Prior Art .................................................... 17
`1.
`Knudsen 2004 (Ex. 1010) ........................................................ 17
`2.
`The Knudsen Patent (Ex. 1012) ............................................... 19
`3.
`Dong (Ex. 1013) ....................................................................... 20
`
`D.
`E.
`
`F.
`
`ii
`
`
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`
`
`I.
`
`J.
`
`Bridon (Ex. 1014) .................................................................... 21
`4.
`Knudsen 2001 (Ex. 1011) ........................................................ 22
`5.
`Legal Standard .................................................................................... 24
`G.
`H. Ground 1: Knudsen 2004 in view of the Knudsen Patent, Dong,
`and Bridon (lead-compound framework) ........................................... 26
`1.
`Claims 1 and 4 .......................................................................... 26
`2.
`Claims 2 and 5 .......................................................................... 42
`3.
`Claims 3 and 6 .......................................................................... 44
`Ground 2: Knudsen 2001 in view of the Knudsen Patent, Dong,
`and Bridon (Lead-Compound Framework) ........................................ 44
`1.
`Claims 1 and 4 .......................................................................... 45
`2.
`Claims 2 and 5 .......................................................................... 50
`3.
`Claims 3 and 6 .......................................................................... 50
`Ground 3: Obviousness over the prior art and common drug
`development principles (under KSR) ................................................. 51
`1.
`If applied as a rigid subject-matter-specific obviousness
`analysis, the lead-compound doctrine is inconsistent with
`KSR ........................................................................................... 51
`Under Graham and KSR, semaglutide would have been
`obvious because the differences between it and the
`closest prior art, liraglutide, involve predictable elements
`and tweaking result-effective variables ................................... 56
`K. Any Secondary Considerations Fail to Overcome Prima Facie
`Obviousness ........................................................................................ 59
`1.
`There were no unexpected or surprising results ...................... 60
`2.
`The prior art did not teach away from semaglutide ................. 61
`3.
`There was no long-felt but unmet need ................................... 61
`4.
`Commercial sales do not save the ’343 patent ......................... 61
`5.
`There was no industry skepticism ............................................ 62
`6.
`Copying by generic drug makers is irrelevant ......................... 62
`VI. This Petition Should Not Be Denied Institution Under 35 U.S.C.
`§ 325(d) ......................................................................................................... 63
`
`2.
`
`iii
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`
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`
`
`A.
`
`This Petition Presents Different Art And Arguments than Were
`Before The Examiner ......................................................................... 64
`The Examiner Materially Erred .......................................................... 68
`B.
`VII. This Petition Should Not Be Denied Institution Under 35 U.S.C. § 314 ..... 69
`VIII. Conclusion .................................................................................................... 70
`
`iv
`
`
`
`
`
`CASES
`
`TABLE OF AUTHORITIES
`
`
`10X Genomics, Inc. v. Bio-Rad Labs., Inc.,
`IPR2021-00133, Paper 11 (PTAB May 14, 2021) ............................................. 68
`
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte GmbH,
`IPR2019-01469, Paper 6 (PTAB Feb. 13, 2020) (precedential) ........................ 64
`
`Altana Pharma AG v. Teva Pharms. USA, Inc.,
`566 F.3d 999 (Fed. Cir. 2009) ............................................................................ 51
`
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, Paper 11 (PTAB Mar. 20, 2020) (precedential) ...................... 69
`
`Aquestive Therapeutics, Inc. v. Neurelis, Inc.,
`IPR2019-00451, Paper 8 (PTAB Aug. 13, 2019) ............................................... 68
`
`Bayer Healthcare Pharms., Inc. v. Watson Pharms., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) .......................................................................... 62
`
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (PTAB Dec. 15, 2017) (precedential) ........................ 63
`
`Daiichi Sankyo Co. v. Matrix Labs., Ltd.,
`619 F.3d 1346 (Fed. Cir. 2010) .................................................................... 24, 52
`
`Donner Tech., LLC v. Pro Stage Gear, LLC,
`979 F.3d 1353 (Fed. Cir. 2020) .......................................................................... 54
`
`E.I. DuPont de Nemours & Co. v. Synvina C.V.,
`904 F.3d 996 (Fed. Cir. 2018) ............................................................................ 25
`
`Eisai Co. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008) .......................................................................... 25
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ............................................................................ 60
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) .............................................................................. 31, 52, 56, 59
`
`v
`
`
`
`
`Henny Penny Corp. v. Frymaster LLC,
`938 F.3d 1324 (Fed. Cir. 2019) .......................................................................... 60
`
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) ........................................................ 25, 42, 50, 56
`
`In re Boesch,
`617 F.2d 272 (CCPA 1980) .............................................................. 25, 55, 57, 59
`
`In re Dillon,
`919 F.2d 688 (Fed. Cir. 1990) (en banc) ............................................................ 51
`
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................................... 60
`
`Intel Corp. v. PACT XPP Schweiz AG,
`No. 2022-1037, slip op. (Fed. Cir. Mar. 13, 2023) ....................................... 54, 56
`
`J.T. Eaton & Co. v. Atl. Paste & Glue Co.,
`106 F.3d 1563 (Fed. Cir. 1997) .......................................................................... 62
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .....................................................................................passim
`
`McNeil-PPC, Inc. v. L. Perrigo Co.,
`337 F.3d 1362 (Fed. Cir. 2003) .......................................................................... 62
`
`Mylan Pharms. Inc. v. Bausch Health Ir. Ltd.,
`IPR2022-00722, Paper 16 (PTAB Sept. 14, 2022)............................................. 25
`
`NOF Corp. v. Nektar Therapeutics,
`IPR2019-01394, Paper 68 (PTAB July 30, 2021) .............................................. 51
`
`Otsuka Pharm. Co. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012) ...................................................................passim
`
`Pentec, Inc. v. Graphic Controls Corp.,
`776 F.2d 309 (Fed. Cir. 1985) ............................................................................ 62
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 59
`
`vi
`
`
`
`
`Sand Revolution II, LLC v. Cont’l Intermodal Grp.,
`IPR2019-01393, Paper 24 (PTAB June 16, 2020) ............................................. 70
`
`Standard Oil Co. v. Am. Cyanamid Co.,
`774 F.2d 448 (Fed. Cir. 1985) ............................................................................ 52
`
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007) .................................................................... 53, 55
`
`Therasense, Inc. v. Becton, Dickinson & Co.,
`593 F.3d 1289 (Fed. Cir. 2010),
`reinstated in relevant part,
`649 F.3d 1276 (Fed. Cir. 2011) (en banc) .................................................... 61, 62
`
`UCB, Inc. v. Accord Healthcare, Inc.,
`890 F.3d 1313, 1329 (Fed. Cir. 2018) ................................................................ 53
`
`Weatherford U.S., L.P. v. Enventure Glob. Tech., Inc.,
`IPR2020-01684, Paper 16 (PTAB Apr. 14, 2021) ............................................. 68
`
`Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc.,
`231 F.3d 1339 (Fed. Cir. 2000) .......................................................................... 51
`
`ZUP, LLC v. Nash Mfg., Inc.,
`896 F.3d 1365 (Fed. Cir. 2018) .......................................................................... 60
`
`STATUTES
`
`35 U.S.C. § 102 ............................................................................................ 52, 53, 55
`
`35 U.S.C. § 102(a) ................................................................................................... 18
`
`35 U.S.C. § 102(b) ............................................................................................passim
`
`35 U.S.C. § 112 ........................................................................................................ 13
`
`35 U.S.C. §§ 311-319................................................................................................. 1
`
`35 U.S.C. § 314 ........................................................................................................ 69
`
`35 U.S.C. § 314(a) ............................................................................................... 6, 69
`
`35 U.S.C. § 325(d) ................................................................................. 63, 64, 68, 69
`
`vii
`
`
`
`
`OTHER AUTHORITIES
`
`37 C.F.R. § 42 ............................................................................................................ 1
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 2
`
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 2
`
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 4
`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 4
`
`37 C.F.R. § 42.10(b) .................................................................................................. 2
`
`37 C.F.R. § 42.15(e) ................................................................................................... 2
`
`37 C.F.R. § 42.22(a) ................................................................................................... 5
`
`37 C.F.R. § 42.63(e) ................................................................................................... 2
`
`37 C.F.R. § 42.100(b) .............................................................................................. 13
`
`37 C.F.R. § 42.103 ..................................................................................................... 2
`
`37 C.F.R. § 42.104(a) ................................................................................................. 5
`
`37 C.F.R. § 42.104(b) ................................................................................................ 5
`
`37 C.F.R. § 42.104(b)(3) .......................................................................................... 13
`
`37 C.F.R. § 42.106(a) ................................................................................................. 2
`
`MPEP 2131.02(I) ..................................................................................................... 67
`
`MPEP 2131.02(III) ................................................................................................... 67
`
`MPEP 2143(I.B) ....................................................................................................... 68
`
`
`
`
`viii
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`TABLE OF EXHIBITS
`
`DESCRIPTION
`
`U.S. Patent No. 8,536,122
`
`U.S. Patent No. 8,129,343
`
`Prosecution history excerpts for U.S. Patent No. 8,536,122
`
`
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`EXHIBIT
`
`1001
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`1002
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`1003
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`1004
`
`Prosecution history excerpts for U.S. Patent No. 8,129,343
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`
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`
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`
`Knudsen, GLP-1 Derivatives as Novel Compounds for the
`Treatment of Type 2 Diabetes: Selection of NN2211 for Clinical
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`
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`
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`Subcutaneous Absorption of a Therapeutic Peptide, 15(2) PHARM.
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`
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`Pharmaceuticals as Therapeutic Agents for the Treatment of
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`
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`
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`the Glucagon-Like Peptides, 127(12) J. CLIN. INVEST. 4217 (2017)
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`1019
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`1021
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`Declaration of Christopher Soares, Ph.D.
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`
`CV of Christopher Soares, Ph.D.
`
`1024
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`Declaration of Paul Dalby, Ph.D.
`
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`
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`
`1027
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`CV of Paul Dalby, Ph.D.
`
`Declaration of John Bantle, MD
`
`CV of John Bantle, MD
`
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`
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`
`Holst, The Incretin Approach for Diabetes Treatment Modulation
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`
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`
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`
`Knudsen, Potent Derivatives of Glucagon-Like Peptide-1 with
`Pharmacokinetic Properties Suitable for Once Daily
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`
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`Luu, Automated Multiple Peptide Synthesis: Improvements in
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`
`Markussen, Soluble, Fatty Acid Acylated Insulins Bind to Albumin
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`
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`
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`
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`DESCRIPTION
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`
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`
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`BEST PRAC. & RSCH. CLINICAL ENDOCRINOLOGY & METABOLISM
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`
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`
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`
`xiv
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`EXHIBIT
`
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`1079
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`1080
`
`1081
`
`Bayliss, The Mechanism of Pancreatic Secretion, 28(5) J.
`PHYSIOLOGY 325 (1902)
`
`Buse, Effects of Exenatide (Exendin-4) on Glycemic Control Over
`30 Weeks in Sulfonylurea-Treated Patients with Type 2 Diabetes,
`27 DIABETES CARE 2628 (2004)
`
`Chang, The GLP-1 Derivative NN2211 Restores β-Cell Sensitivity
`to Glucose in Type 2 Diabetic Patients After a Single Dose, 52
`DIABETES 1786 (2003)
`
`Degn, One Week’s Treatment with the Long-Acting Glucagon-Like
`Peptide 1 Derivative Liraglutide (NN2211) Markedly Improves 24-
`h Glycemia and α- and β-Cell Function and Reduces Endogenous
`Glucose Release in Patients with Type 2 Diabetes, 53 DIABETES
`1187 (2004)
`
`1082
`
`Edwards, GLP-1: Target for a New Class of Antidiabetic Agents?,
`97 J. R. SOC. MED. 270 (2004)
`
`1083
`
`1084
`
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`Elbrond, Pharmacokinetics, Pharmacodynamics, Safety, and
`Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-
`Like Peptide 1 Derivative, in Healthy Male Subjects, 25 DIABETES
`CARE 1398 (2002)
`
`Gault, Glucose-Dependent Insulinotropic Polypeptide Analogues
`and Their Therapeutic Potential for the Treatment of Obesity-
`Diabetes, 308 BIOCHEM. & BIOPHYSICAL RSCH. COMMC’NS 207
`(2003)
`
`Harder, The Effect of Liraglutide, a Long-Acting Glucagon-Like
`Peptide 1 Derivative, on Glycemic Control, Body Composition, and
`24-h Energy Expenditure in Patients with Type 2 Diabetes, 27
`DIABETES CARE 1915 (2004)
`
`Larsen, Systemic Administration of the Long-Acting GLP-1
`Derivative NN2211 Induces Lasting and Reversible Weight Loss in
`Both Normal and Obese Rats, 50 DIABETES 2530 (2001)
`
`xv
`
`
`
`
`
`EXHIBIT
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`DESCRIPTION
`
`1087
`
`1088
`
`1089
`
`1090
`
`1091
`
`1092
`
`1093
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`Ribel, NN2211: A Long-Acting Glucagon-Like Peptide-1
`Derivative with Anti-Diabetic Effects in Glucose-Intolerant Pigs,
`451 EUR. J. PHARMACOLOGY 217 (2002)
`
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`MacDonald, The Multiple Actions of GLP-1 on the Process of
`Glucose-Stimulated Insulin Secretion, 51 (suppl. 3) DIABETES S434
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`as Tumor Specific Contrast Agents in MRI, 126 J. AM. CHEM. SOC.
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`
`Autio, Mini-PEG Spacering of VAP-1-Targeting 68Ga-DOTAVAP-
`P1 Peptide Improves PET Imaging of Inflammation, 1 EJNMMI
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`ANAESTHESIA 599 (2000)
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`EXHIBIT
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`1100
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`DESCRIPTION
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`Holst, Implementation of GLP-1 Based Therapy of Type 2 Diabetes
`Mellitus Using DPP-IV Inhibitors, in DIPEPTIDYL
`AMINOPEPTIDASES IN HEALTH AND DISEASE (Martin Hildebrandt et
`al. eds., 2003)
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`Transfer Order, In re: Ozempic (Semaglutide) Patent Litigation,
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`INVESTIGATIONAL DRUGS 1245 (2003)
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`
`1109
`
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`
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`
`1112
`
`
`
`xvii
`
`
`
`
`
`I.
`
`INTRODUCTION
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) petitions for inter partes review of
`
`claims 1-6 (“the challenged claims”) of U.S. Patent No. 8,129,343 (“the ’343
`
`patent”) (Ex. 1001), which is assigned to Novo Nordisk A/S (“Patent Owner”), under
`
`35 U.S.C. §§ 311-319 and 37 C.F.R. § 42. Petitioner seeks a determination that those
`
`claims be canceled as unpatentable.
`
`The ’343 patent claims glucagon-like peptide 1 (“GLP-1”) analogue
`
`compounds that may be useful in treating type-2 diabetes, among other conditions.
`
`GLP-1 is a peptide hormone produced in the human body that promotes insulin
`
`secretion. Because native GLP-1 breaks down within minutes, researchers have long
`
`investigated chemically modified GLP-1 peptides (i.e., analogues) with extended
`
`durations of action (e.g., longer half-lives) to make a suitable drug product. Through
`
`these studies, scientists have discerned which parts of GLP-1 are important to its
`
`activity and which are amenable to changes, and what sort of changes should be
`
`made to extend the compound’s half-life. Patent Owner itself has produced prior art
`
`GLP-1 analogues, some with good pharmacological activity. The prior art was
`
`therefore replete with information concerning GLP-1 and its analogues, serving as a
`
`catalog of known variables and solutions from which scientists could choose to make
`
`new analogues.
`
`1
`
`
`
`
`
`Patent Owner made and characterized its first-generation GLP-1 analogue,
`
`called liraglutide, well before the priority date of the ’343 patent. Using the catalog
`
`of well-known variables and solutions, Patent Owner made a few trivial changes to
`
`liraglutide to make its second-generation compound—semaglutide—which is
`
`encompassed by the challenged claims. But these trivial changes do not warrant
`
`patent protection; they fall squarely in the realm of obviousness. The Board should
`
`cancel these claims.
`
`II. MANDATORY NOTICES
`
`This Petition is filed in accordance with 37 C.F.R. § 42.106(a). Filed herewith
`
`is a power of attorney and exhibit list per § 42.10(b) and § 42.63(e). Under 37 C.F.R.
`
`§ 42.103, the fee set forth in § 42.15(e) accompanies this Petition.
`
`A. Real Parties-In-Interest
`
`In accordance with 37 C.F.R. § 42.8(b)(1), the real parties-in-interest for
`
`Petitioner are Mylan Pharmaceuticals Inc., Mylan Inc., and Viatris Inc.
`
`B. Related Matters
`
`In accordance with 37 C.F.R. § 42.8(b)(2), Petitioner is not aware of any
`
`reexamination certificates or pending prosecution concerning the ’343 patent.
`
`Petitioner is a defendant in the following litigation involving the ’343 patent:
`
` Novo Nordisk Inc. v. Mylan Pharmaceuticals Inc.,
`No. 22-cv-01040-CFC (D. Del.);
`
`2
`
`
`
`
`
` Novo Nordisk Inc. v. Viatris Inc.,
`No. 1:23-cv-00013-TSK (N.D. W. Va.);
` Novo Nordisk Inc. v. Viatris Inc.,
`No. 1:23-cv-00101-CFC (D. Del);
` In re: Ozempic (Semaglutide) Patent Litig.,
`No. 22-md-3038-CFC (D. Del.).
`
`In addition, the following litigations also involve the ’343 patent:
`
` Novo Nordisk Inc. v. Aurobindo Pharma USA, Inc.,
`No. 1:22-cv-00295 (D. Del.) (dismissed on March 28, 2022).
` Novo Nordisk Inc. v. Rio Biopharmaceuticals, Inc.,
`No. 1:22-cv-00294 (D. Del.)
` Novo Nordisk A/S v. Sun Pharm. Indus. Ltd.,
`No. 1:22-cv-00296 (D. Del.)
` Novo Nordisk Inc. v. Zydus Worldwide DMCC,
`No. 1:22-cv-00297 (D. Del.)
` Novo Nordisk Inc. v. Dr. Reddy’s Labs. Ltd.,
`No. 1:22-cv-00298 (D. Del.)
` Novo Nordisk Inc. v. Alvogen, Inc.,
`
`No. 1:22-cv-00299 (D. Del.)
`
`Petitioner is concurrently filing a petition for one other patent in the same
`
`family as the ’343 patent: U.S. Patent No. 8,536,122.
`
`Petitioner is not aware of any other pending litigation, or any pending
`
`proceedings before the Patent Trial and Appeal Board.
`
`3
`
`
`
`
`
`C.
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel
`Brandon M. White
`Reg No. 52,354
`Perkins Coie LLP
`700 13th Street NW, Ste 800
`Washington, DC 20005
`Phone: (202) 654-6200
`Back-Up Counsel
`Courtney Prochnow, Ph.D.
`Reg. No. 67,639
`Perkins Coie LLP
`633 W. 5th St., Ste 5850
`Los Angeles, CA 90071
`Phone: (310) 788-9900
`Back-Up Counsel
`Jonathan I. Tietz, Ph.D.
`Reg No. 76,753
`Perkins Coie LLP
`700 13th Street NW, Ste 800
`Washington, DC 20005
`Phone: (202) 654-6200
`
`Back-Up Counsel
`Emily J. Greb
`Reg No. 68,244
`Perkins Coie LLP
`33 East Main Street, Ste 1
`Madison, WI 53703
`Phone: (608) 663-7460
`Back-Up Counsel
`Christopher D. Jones
`Reg No. 76,472
`Perkins Coie LLP
`700 13th Street, NW, Ste 800
`Washington, DC 20005
`Phone: (202) 654-6200
`Back-Up Counsel
`Matthew A. Lembo
`Reg No.