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`UNITED STATES PATENT AND TRADEMARK OFFICE
`______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________
`
`MYLAN INSTITUTIONAL LLC AND PFIZER INC.,
`Petitioners,
`
`v.
`
`NOVO NORDISK A/S,
`Patent Owner.
`______________
`
`Case IPR2020-003241
`Patent 8,114,833
`______________
`
`
`PATENT OWNER SUR-REPLY
`
`
`
`
`
`
`1 IPR2020-01252 has been joined with this proceeding.
`
`
`
`

`

`
`
`TABLE OF CONTENTS
`
`IPR2020-00324
`Patent 8,114,833
`
`Page
`
`I.
`
`INTRODUCTION ........................................................................................... 1
`
`II.
`
`GROUND 1: FLINK DOES NOT ANTICIPATE CLAIMS 1-15 ................. 4
`
`A.
`
`B.
`
`C.
`
`Flink Does Not Lead a Skilled Artisan To “Immediately
`Envision” the Claimed Formulations .................................................... 4
`
`Consideration of Flink as a “Whole,” Shows There Is No
`Anticipation ........................................................................................... 6
`
`The Remainder of Petitioner’s Arguments Do Not Advance Its
`Anticipation Theory .............................................................................. 7
`
`III. GROUND 2: CLAIMS 1-15 WOULD NOT HAVE BEEN OBVIOUS
`OVER FLINK .................................................................................................. 9
`
`A.
`
`Petitioner Has Not Shown a Motivation to Combine, Nor a
`Reasonable Expectation of Success ...................................................... 9
`
`B.
`
`Novo Nordisk’s Interpretation of Flink’s Disclosure Is Correct ........ 11
`
`IV. THE PREAMBLES OF CLAIMS 23-31 ARE LIMITING .......................... 11
`
`V.
`
`CLAIMS 1-31 WOULD NOT HAVE BEEN OBVIOUS OVER FLINK
`IN VIEW OF BETZ....................................................................................... 13
`
`VI. BETZ IS NOT PRIOR ART TO THE ’833 PATENT .................................. 16
`
`VII. NOVO NORDISK REDUCED THE CLAIMED INVENTIONS TO
`PRACTICE BY AT LEAST
` .............................................. 17
`
`VIII. SECONDARY CONSIDERATIONS STRONGLY REFUTE ANY
`SHOWING OF OBVIOUSNESS .................................................................. 20
`
`IX. DR. FORREST’S REPLY DECLARATION IS IMPROPER ...................... 23
`
`X.
`
`CONCLUSION .............................................................................................. 25
`
`
`
`ii
`
`

`

`TABLE OF AUTHORITIES
`
`IPR2020-00324
`Patent 8,114,833
`
`Page(s)
`
`
`
`
`CASES
`
`Allergan, Inc. v. Sandoz Inc.,
`796 F.3d 1293 (Fed. Cir. 2015) .................................................................... 16, 21
`
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp.,
`320 F.3d 1339 (Fed. Cir. 2003) .......................................................................... 12
`
`Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) ............................................................................ 20
`
`Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc.,
`769 F.3d 1339 (Fed. Cir. 2014) .......................................................................... 22
`
`Complex Innovations, LLC v. AstraZeneca AB,
`IPR2017-00631, Paper No. 13 (P.T.A.B. July 24, 2017) ..................................... 6
`
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`800 F.3d 1375 (Fed. Cir. 2015) .......................................................................... 17
`
`Eaton Corp. v Rockwell Int’l Corp.,
`323 F.3d 1332 (Fed. Cir. 2003) .......................................................................... 12
`
`Genetics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc.,
`655 F.3d 1291 (Fed. Cir. 2011) .......................................................................... 22
`
`Google LLC v. Koninklijke Philips N.V.,
`789 Fed. App’x 874 (Fed. Cir. 2019) ................................................................. 17
`
`Griffin v. Bertina,
`285 F.3d 1029 (Fed. Cir. 2002) .......................................................................... 12
`
`Henny Penny Corp. v. Frymaster LLC,
`938 F.3d 1324 (Fed. Cir. 2019) .......................................................................... 17
`
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................................... 22
`
`iii
`
`

`

`IPR2020-00324
`Patent 8,114,833
`
`
`In re Kotzab,
`217 F.3d 1365 (Fed. Cir. 2000) ............................................................................ 9
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .......................................................................... 22
`
`In re Stepan Co.,
`868 F.3d 1342 (Fed. Cir. 2017) ............................................................................ 9
`
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) ...................................................................passim
`
`Lupin Ltd. v. Senju Pharm. Co., Ltd.,
`IPR2015-01099, Paper 69 (P.T.A.B. Sept. 12, 2016) ................................... 15, 25
`
`MoneyIN, Inc. v. VeriSign, Inc.,
`545 F.3d 1359 (Fed. Cir. 2008) ............................................................................ 1
`
`Orexo AB v. Actavis Elizabeth LLC,
`903 F.3d 1265 (Fed. Cir. 2018) .......................................................................... 21
`
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) ............................................................................ 5
`
`SmithKline Beecham Corp. v. Apotex Corp.,
`403 F.3d 1331 (Fed. Cir. 2005) ............................................................................ 8
`
`Toyota Motor Corp. v. Am. Vehicular Sci. LLC,
`IPR2013-00424, Paper 50 (P.T.A.B. Jan. 12, 2015) .......................................... 23
`
`STATUTES AND RULES
`
`37 C.F.R. 42.22 ...................................................................................... 13, 14, 17, 23
`
`35 U.S.C. § 312(a)(3) ......................................................................................... 13, 23
`
`
`
`
`
`
`
`
`
`iv
`
`

`

`TABLE OF EXHIBITS
`
`EXH]BIT
`
`DESCRIPTION
`
`IPR2020-00324
`
`Patent 8,114,833
`
`Declaration of Ryan P. Johnson in Support of Patent Owner’s
`Motion for Admission Pro Hac Vice of Ryan P. Johnson Under 37
`C.F.R.
`42.10 c
`
`Declaration of Laura T. Moran in Support of Patent Owner’s Motion for
`Admission Pro Hac Vice of Laura T. Moran Under 37 C.F-R. § 42.10 c
`Chien-Hua Niu, FDA Perspective on Peptide Formulation and
`'
`7
`Issues, 87 J. PHARM. SCIENCES 1331 1998
`' ”
`
`C. Goolcharran, et al., Chemical Pathways ofPeptide and Protein
`Degradation, in PHARMACEUTICAL FORMULATION
`DEVELOPMENT OF PEPTIDES AND PROTEINS 70 (Sven Frokjaer
`& Lars Hov aard eds-,2000 “Goolcharran”
`
`Mark C. Manning et al., Stability ofProtein Pharmaceuticals, 6
`PHARM. RESEARCH 903 1989 “Mannin ”
`
`R.W. Payne, et al., Peptide Formulation: Chalenges and Strategies,
`INNOVATIONS PHARM- TECH. 64 2009 “
`”
`
`E.T. Kaiser et al., Secondary structures ofproteins and peptides in
`amphiphilic environments (A Review), 80 PROC. NATL. ACAD. SCI.
`USA 1137 1983
`“Kaiser”
`
`Dean K. Clodfelter et al., Efiects ofNon-Covalent Self-Association
`on the Subcutaneous Absalption ofa Therapeutic Peptide, 15
`PHARM. RES. 254 1998
`“Clodfelter”
`
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`
`Eva Y. Chi et al., Physical Stability ofProteins in Aqueous Solution:
`Mechanism and Driving Forces in Normative Protein Aggregation,
`
`20 PHARM. RESEARCH 1325 (2003) (“Chi”)
`US. Patent No. 5,932,547
`
`Lotte Knudsen, et al., Potent Derivatives of Glucagon-like Peptide-I
`with Pharmacokinetic Properties Suitablefor Once Daily
`Administration, 43 J. MED. CHEM. 1664 2000 “Knudsen 2000”
`
`US. Patent A . . lication Publication No. 2002/0061838
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`Humira® Packa_e Insert revised 01/2003
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`United States Pharmacopeia and National Formulary (USP 26-NF
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`
`2016
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`Alfred Doenicke, et al., Osmolalities ofPropylene Glycol-
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`Pro lene Gl col Be Used as a Solvent?, 75 ANESTH. ANALG. 431
`
`

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`Patent 8,114,833
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`(1992) (“Doenicke”)
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`Kenneth Strauss et al., A pan‐European epidemiologic study of
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`Biosimilar Development and the BPCI Act (Revision 2), Guidance
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`Declaration of Peter M. Tessier, Ph.D. dated September 18, 2020
`(Confidential – Protective Order Material)
`Declaration of Dorthe Kot Engelund dated September 16, 2020
`(Confidential – Protective Order Material)
`Declaration of Tina Bjeldskov Pedersen, Ph.D. dated September 17, 2020
`Declaration of David Nolan dated September 17, 2020
`Curriculum Vitae of Peter M. Tessier (dated 09/2020)
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`Fu, R. C. C., et al. The biocompatibility of parenteral vehicles—in
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`Naccache, P., & Sha'afi, R. I. Patterns of nonelectrolyte permeability in
`human red blood cell membrane. 62 THE JOURNAL OF GENERAL
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`(2001)
`Patel, N., & Newsham, L. G., Experiments in Physical Pharmacy. VI.
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`current techniques. 1 JOURNAL OF HEMATOTHERAPY, 233-250 (1992)
`Schellekens, H. Bioequivalence and the immunogenicity of
`biopharmaceuticals. 1 NATURE REVIEWS DRUG DISCOVERY, 457-462
`(2002) (“Schellekens”)
`Senderoff, R. I., et al. Consideration of conformational transitions and
`racemization during process development of recombinant glucagon-like
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`Setnikar, I., & Temelcou, O. Osmotic concentration and osmotic
`pressure in injectable solutions. 48 JOURNAL OF THE AMERICAN
`PHARMACEUTICAL ASSOCIATION (SCIENTIFIC ED.), 628-630 (1959)
`(“Setnikar & Temelcou”)
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`vii
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`2051
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`Stratton, L. P., et al. Controlling deamidation rates in a model peptide:
`Effects of temperature, peptide concentration, and additives. 90 JOURNAL
`OF PHARMACEUTICAL SCIENCES, 2141-2148 (2001)
`Sztein, J. M., et al. Comparison of permeating and nonpermeating
`cryoprotectants for mouse sperm cryopreservation. 42
`CRYOBIOLOGY, 28-39 (2001) (“Sztein”)
`Thorens, B., & Waeber, G. Glucagon-like peptide-I and the control of
`insulin secretion in the normal state and in NIDDM. 42 DIABETES, 1219-
`1225 (1993)
`Yang, X., et al. Subzero nonfreezing storage of the mammalian cardiac
`explant: I. Methanol, ethanol, ethylene glycol, and propylene glycol as
`colligative cryoprotectants. 30 CRYOBIOLOGY, 366-375 (1993)
`Wolffenbuttel, B. H., & Graal, M. B. New treatments for patients with
`type 2 diabetes mellitus. 72 POSTGRADUATE MEDICAL JOURNAL, 657-662
`(1996)
`Highlights of Prescribing Information, Revised 08/2020 (“Victoza®
`Prescribing Information”)
`Internal Novo Nordisk Report, dated December 3, 2001 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Email Chain, beginning December 19, 2001 and
`certified translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Report, dated December 19, 2001 and certified
`translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Protocol, dated January 22, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`De Vos, A. M., et al. Human growth hormone and extracellular domain
`of its receptor: crystal structure of the complex. 255 SCIENCE, 306-312
`(1992)
`Internal Novo Nordisk Meeting Minutes, dated April 12, 2002 and
`certified translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Protocol, dated April 29, 2002 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Protocol, dated June 3, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Study Plan, dated June 5, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Memo, dated June 27, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`
`viii
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`

`
`2060
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`2061
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`2062
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`2063
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`2064
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`2065
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`2066
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`2067
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`2068
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`2069
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`2070
`
`2071
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`2072
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`2073
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`2074
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`2075
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`2076
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`2077
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`2078
`2079
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`IPR2020-00324
`Patent 8,114,833
`
`Internal Novo Nordisk Study Plan, dated July 23, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`Center for Drug Evaluation and Research “Final Printed Labeling –
`Application Number 21-319: FORTEO” (2002)
`Internal Novo Nordisk Lab Notebook (excerpt), dated July 24, 2002 and
`certified translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Meeting Minutes, dated November 14, 2002 and
`certified translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Design Review Presentation, dated November 29,
`2002 (Confidential – Protective Order Material)
`Internal Novo Nordisk Meeting Minutes, dated February 3, 2003 and
`certified translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Statement, dated April 9, 2003 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Report, dated April 10, 2003 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Report, dated April 22, 2003 (Confidential –
`Protective Order Material) (“April 22, 2003 Report”)
`Internal Novo Nordisk Report, dated June 10, 2003 and certified
`translation thereof (Confidential – Protective Order Material)
`Internal Novo Nordisk Trial Protocol, dated June 11, 2003 (Confidential
`– Protective Order Material)
`Internal Novo Nordisk Report, dated June 18, 2003 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Report, dated June 27, 2003 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Protocol, dated January 30, 2018 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Report, dated May 17, 2018 (Confidential –
`Protective Order Material)
`Internal Novo Nordisk Report, dated May 17, 2018 (Confidential –
`Protective Order Material)
`Berg, J. M. et al. Biochemistry: Chapter 3: Protein Structure and
`Function, 5 W.H. FREEMAN AND COMPANY, 41-76 (2002) (“Berg”)
`Physician’s Desk Reference, 54th ed., “Norditropin” pp. 2061-2062
`(2000)
`Physician’s Desk Reference, Supplement A, “Humira” pp. A5-A6 (2003)
`Deposition Transcript of Laird Forrest, Ph.D., dated September 3, 2020
`
`ix
`
`

`

`
`2080
`
`2081
`
`2082
`
`2083*
`
`2084*
`
`2085*
`
`2086*
`
`2087*
`
`2088*
`
`2089*
`
`2090*
`
`2091*
`
`2092*
`
`IPR2020-00324
`Patent 8,114,833
`
`Redacted Version of Declaration of Peter Tessier, Ph.D. dated September
`18, 2020
`Remington’s Pharmaceutical Science, Vol. I, 19th ed., Chapter 36 (1995)
`(“Remington 1995”)
`Claim Construction Order in Novo Nordisk Inc. et al. v. Mylan
`Institutional LLC, C.A. No. 19-1551 (CFC) (SRF), D.I. 106 (D. Del.
`Sept. 17, 2020)
`Supplemental Evidence to Resolve Objection to Exhibit 2051: Internal
`Novo Nordisk Email Chain, beginning December 19, 2001 and certified
`translation thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2052: Internal
`Novo Nordisk Report, dated December 19, 2001 and certified translation
`thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2053: Internal
`Novo Nordisk Protocol, dated January 22, 2002 and certified translation
`thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2055: Internal
`Novo Nordisk Meeting Minutes, dated April 12, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2057: Internal
`Novo Nordisk Protocol, dated June 3, 2002 and certified translation
`thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2058: Internal
`Novo Nordisk Study Plan, dated June 5, 2002 and certified translation
`thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2059: Internal
`Novo Nordisk Memo, dated June 27, 2002 and certified translation
`thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2060: Internal
`Novo Nordisk Study Plan, dated July 23, 2002 and certified translation
`thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2062: Internal
`Novo Nordisk Lab Notebook (excerpt), dated July 24, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2063: Internal
`Novo Nordisk Meeting Minutes, dated November 14, 2002 and certified
`translation thereof (Confidential – Protective Order Material)
`
`x
`
`

`

`IPR2020-00324
`Patent 8,114,833
`
`
`2093*
`
`2094*
`
`2095
`
`2096
`
`2097
`
`Supplemental Evidence to Resolve Objection to Exhibit 2065: Internal
`Novo Nordisk Meeting Minutes, dated February 3, 2003 and certified
`translation thereof (Confidential – Protective Order Material)
`Supplemental Evidence to Resolve Objection to Exhibit 2069: Internal
`Novo Nordisk Report, dated June 10, 2003 and certified translation
`thereof (Confidential – Protective Order Material)
`Witte, R., & Witte, J. Chapter 11: More about Hypothesis Testing. 11
`STATISTICS, 195-220 (2017)
`Deposition Transcript of Laird Forrest, Ph.D., dated January 21, 2021
`(Confidential – Protective Order Material)
`Redacted Version of Deposition Transcript of Laird Forrest, Ph.D., dated
`January 21, 2021
`
` *
`
` Indicates that the Exhibit was served on Petitioner Mylan Institutional LLC, but
`was not filed.
`
`xi
`
`

`

`IPR2020-00324
`Patent 8,114,833
`
`
`I.
`
`INTRODUCTION
`
`Petitioner’s Reply is long on rhetoric extolling the disclosures of its primary
`
`references, but short on evidence addressing limitations not disclosed in or taught by
`
`the prior art. Petitioner identifies Flink’s claim 14 as its alleged anticipatory
`
`disclosure, deeming Flink “the epitome[e]” of anticipation. Paper 2 at 28-31; Paper
`
`35 at 5. Not so. Claim 14 has sixty different chains of dependency, and the chain
`
`that Petitioner has outlined embraces 216 potential combinations of isotonicity agent
`
`and buffer, if limited to agents disclosed in the specification, for which there is no
`
`reason to do so. Neither Petitioner, nor its expert, have addressed the sheer number
`
`of possible formulations available in practicing claim 14. Nothing in claim 14, or
`
`anywhere in Flink, would have directed a skilled artisan to the specific claimed
`
`combination. Petitioner necessarily turns a blind eye to Flink’s examples,
`
`comprising at least 30 formulations, and its 75+ “typical” formulations, which
`
`contain either mannitol or glycerol, without describing a single formulation
`
`containing propylene glycol in any concentration, nor combining it with disodium
`
`phosphate dihydrate as the ’833 patent’s claims require.
`
`Anticipation requires the prior art show “all of the limitations arranged or
`
`combined in the same way as recited in the claims.” MoneyIN, Inc. v. VeriSign, Inc.,
`
`545 F.3d 1359, 1371 (Fed. Cir. 2008); Paper 25 at 16-17 n.1. A skilled artisan
`
`reading Flink would not find propylene glycol arranged in any formulation, much
`
`1
`
`

`

`IPR2020-00324
`Patent 8,114,833
`
`
`less one that falls within the claims of the ’833 patent. Nor does Petitioner’s Reply
`
`overcome Flink’s failure to describe any concentration of propylene glycol, much
`
`less the claimed concentrations (1-100 mg/ml, 1-50 mg/ml, 5-25 mg/ml, and 8-16
`
`mg/ml). Stripped of hyperbole, Petitioner’s Reply—and its entire case—rise and
`
`fall on Flink’s passing mention of propylene glycol as an exemplary polyhydric
`
`alcohol. This is not enough to anticipate the challenged claims.
`
`Petitioner further argues that because the claims of Flink’s U.S. counterpart
`
`(the “’618 patent”) cover Novo Nordisk’s Victoza®, Flink must anticipate the claims
`
`of the ’833 patent, which also cover Victoza®,, because “that which infringes if later,
`
`anticipates if earlier.” Paper 35 at 8. There is nothing preventing a given
`
`formulation from infringing the ’618 patent (i.e., Flink) but not the ’833 patent. The
`
`fact that the ’618 patent covers one aspect of Victoza® does not establish that its
`
`disclosure anticipates a patent covering another aspect (i.e., the ’833 patent). By
`
`Petitioner’s logic, Novo Nordisk’s patent covering Victoza®’s active ingredient must
`
`anticipate the ’833 patent because they both cover aspects of Victoza®. This is both
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`a logical fallacy and a distraction.
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`Petitioner’s obviousness theory is no more persuasive. When read for all it
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`teaches, Flink directs persons of skill to practice formulations with mannitol, not
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`propylene glycol. Petitioner claims a skilled artisan would have reasons to fear using
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`mannitol as an isotonic agent because it could cause deposits, but the prior art does
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`not bear
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`this out.
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` On
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`the contrary,
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`leading
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`treatises
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`recommend
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`mannitol.
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` Petitioner’s effort
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`to
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`rebut
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`this with
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`references concerning
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`cardiopulmonary bypass surgery and supersaturated solutions to prevent kidney
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`failure falls flat. Conversely, the prior art taught that the solvent propylene glycol
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`could cause stability problems, tissue damage, and hemolysis, effects that would
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`have been antithetical to its tonicity function. The art even goes so far as
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`recommending removing it from parenteral formulations. All this is evident from
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`exhibits that Petitioner relies on. Nothing in Flink or any other reference provides
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`the requisite motivation to combine propylene glycol, instead of mannitol, with
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`disodium phosphate dihydrate, or an expectation that a formulation doing so would
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`be successful.
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`Petitioner’s third ground fails, too. Petitioner’s attempt, for the first time in
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`its Reply, to claim an earlier priority date for Betz is untimely and should be
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`rejected. Betz is not prior art because the ’833 patent inventors reduced the claimed
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`inventions to practice by at least April 2003. However, even if Betz were prior art,
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`the claims of the ’833 patent would not have been obvious over Flink in view of
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`Betz. First, there is no motivation absent hindsight to combine Flink (regarding
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`GLP-1) and Betz (regarding hGH), because they concern molecules of different
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`sizes, properties, and activities. Confronted with these differences, Petitioner’s
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`expert belatedly offers a host of complicated justifications for why a skilled artisan
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`would view them as similar, but the prior art contains no hint of this connection. In
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`any event, both Flink and Betz are united in their preference for mannitol, teaching
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`away from the ’833 patent’s directive to replace it.
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`II. GROUND 1: FLINK DOES NOT ANTICIPATE CLAIMS 1-15
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`A.
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`Flink Does Not Lead a Skilled Artisan To “Immediately Envision”
`the Claimed Formulations
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`Petitioner’s Reply does not correct the significant holes in its anticipation
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`theory. Instead of addressing the shortcomings identified in the Patent Owner
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`Response (Paper 25 at 16, 18-23, 30-34), Petitioner generalizes and overstates
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`Flink’s disclosure as the “epitom[e]” of an anticipatory disclosure. Paper 35 at 5.
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`But Flink does not describe a GLP-1 agonist formulation containing propylene
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`glycol and disodium phosphate dihydrate, despite Petitioner’s repeated insistence
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`otherwise. See Paper 35 at 13. Instead, Petitioner’s anticipation theory hinges on
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`isolated mentions of propylene glycol and disodium phosphate dihydrate, and the
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`false premise that a skilled artisan would have “immediately envisioned” their
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`combination.
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`Petitioner and its expert pin their anticipation argument on Flink’s claim 14,
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`(Paper 35 at 22-23), as it depends from 7 other claims. This is just one of sixty
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`potential chains of claim dependency flowing from claim 14, and Petitioner gives no
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`justification for choosing this one, other than its expert’s telling admission that it
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`provided him with what he needed for his anticipation argument. Ex2096, 21:11-
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`22:12; 24:19-25. But Flink’s claims require only an “isotonic agent” and a “buffer,”
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`without specifying which ones. So, to find the specific excipients claimed in the
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`’833 patent, Petitioner pivots to Flink’s specification—specifically, a passage on
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`isotonic agents that lists 18 chemicals, and a passage on buffers that lists 12. This
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`yields 216 potential isotonic agent and buffer combinations (although Petitioner’s
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`expert testified that all non-novel excipients—at least a “few dozen”—would be
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`available to a skilled artisan as options). Id., 40:22-42:7. The question, then, is
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`whether anything in Flink causes a skilled artisan to “immediately envision” the one
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`of those 216 that would satisfy the ’833 patent’s claims. Flink contains no such
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`teaching.
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`Petitioner relies on Perricone v. Medicis Pharm. Corp., 432 F.3d 1368 (Fed.
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`Cir. 2005), which involved just one list, limited to 14 chemicals. Id. at 1376. Even
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`if a skilled artisan limited himself to the chemicals disclosed in the Flink
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`specification, he would face 216 possible combinations, and only one meeting the
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`claims of the ’833 patent. Flink contains nothing that singles out that combination.
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`On the contrary, Flink consistently and repeatedly directs skilled artisans to other
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`combinations. The absence of an instruction not to combine claim elements is far
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`from the required showing that a skilled artisan would have “immediately
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`envisioned” combining them.
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`Furthermore, Flink does not disclose any concentration of propylene glycol,
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`let alone the narrower claimed ranges of 1-50 mg/ml, 5-25 mg/ml, or 8-16 mg/ml,
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`recited in dependent claims 2, 3, and 4 of the ’833 patent. Dr. Forrest admitted that
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`Flink does not describe any concentration of propylene glycol. Ex2079, 119:20-24,
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`120:14-17. A general concentration range of an “isotonicity agent” does not
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`anticipate a concentration of a specific chemical, especially the narrowed claimed
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`ranges. See Complex Innovations, LLC v. AstraZeneca AB, IPR2017-00631, Paper
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`No. 13, 8-9 (P.T.A.B. July 24, 2017) (declining to institute anticipation challenge
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`relying on a broad range to anticipate specific values).
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`Nor does Flink dispel significant prior art concerns with propylene glycol that
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`would have given a skilled artisan pause. In its Reply, Petitioner claims that a skilled
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`artisan would have known that these negative properties were observed through in
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`vitro studies and therefore would have discounted them. Paper 35 at 15-16. But
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`none of the references contain any such caveat. Paper 25 at 7-9, Ex2022, ¶¶68-79.
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`The prior art does not support Petitioner’s post hac attempt to explain them away.
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`B. Consideration of Flink as a “Whole,” Shows There Is No
`Anticipation
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`Novo Nordisk rebutted Petitioner’s reliance on Flink’s Example 7 in the
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`Patent Owner Response. Paper 25 at 22, 25, 42. Now, Petitioner tries to change the
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`narrative, arguing that it was Novo Nordisk who “focus[ed] on Example 7.” Paper
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`35 at 11. To be clear, Novo Nordisk addressed Example 7 only because Petitioner
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`and the Board first raised it, (Paper 2 at 40-42, 48; Paper 13 at 9, 15), unsurprisingly,
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`given that it is the only place Flink mentions disodium phosphate dihydrate, which
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`the ’833 patent’s claims require. Ex1004 at 45-46.
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`In its discussion of Example 7, Petitioner argues that “for anticipation one
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`looks to the whole reference.” Paper 35 at 12. But considering the “whole
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`reference” is exactly what Novo Nordisk urges the Board to do. As a whole, Flink
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`directs skilled artisans to formulations containing mannitol and glycerol, not
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`propylene glycol. Conversely, Petitioner focuses on specific excerpts, read in
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`isolation (one of Flink’s 32 claims, one specific buffer disclosed in only Example 7,
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`and one specific chemical disclosed only once as an example of a polyhydric
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`alcohol). It is Petitioner, not Novo Nordisk, who ignores the bulk of Flink.
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`C. The Remainder of Petitioner’s Arguments Do Not Advance Its
`Anticipation Theory
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`Petitioner takes exception to Novo Nordisk asserting both the U.S. counterpart
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`to Flink (the “’618 patent”) and the ’833 patent against it, while maintaining that
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`Flink does not anticipate the ’833 patent. Petitioner argues “that which infringes if
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`later, anticipates if earlier,” suggesting that Petitioner’s infringement of the ’618
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`patent establishes that the ’618 patent’s disclosure (i.e., Flink) must anticipate the
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`’833 patent. Paper 35 at 8. But the maxim rings hollow here. Neither the claims of
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`Flink nor the ’618 patent include limitations to the specific isotonicity agent or buffer
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`claimed in the ’833 patent. Flink and the ’618 patent contain genus disclosures and
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`claims, while the ’833 patent contains a species disclosure and claims. Petitioner
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`may infringe both the genus and the species claims, which it does, without the genus
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`disclosure anticipating the species disclosure, as is the case here. Petitioner can
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`infringe two patents that cover different aspects of Victoza®’s formulation, without
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`compelling the conclusion that one must anticipate the other.
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`SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331 (Fed. Cir. 2005)
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`is distinguishable. It did not involve a genus-species relationship, but rather inherent
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`anticipation of a polymorph patent, by attempting to make an anhydrate, but
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`inevitably producing a hemihydrate. Probing beyond sound bites from SmithKline
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`revea