Trials@uspto.gov
`571-272-7822
`
`
`
`Paper 12
`Date: June 23, 2020
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN INSTITUTIONAL LLC,
`Petitioner,
`
`v.
`
`NOVO NORDISK A/S,
`Patent Owner.
`
`IPR2020-00324
`Patent 8,114,833 B2
`
`
`
`
`
`
`
`
`
`Before ERICA A. FRANKLIN, JOHN G. NEW, and
`SUSAN L.C. MITCHELL, Administrative Patent Judges.
`
`FRANKLIN, Administrative Patent Judge.
`
`DECISION
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314
`
`
`
`
`
`
`
`

`

`IPR2020-00324
`Patent 8,114,833 B2
`
`I.
`
`INTRODUCTION
`
`Mylan Institutional LLC (“Petitioner”) filed a Petition requesting an
`
`inter partes review of claims 1–31 of U.S. Patent No. 8,114,833 B2
`
`(Ex. 1001, “the ’833 patent”). Paper 2 (“Petition” or “Pet.”). Novo Nordisk
`
`A/S (“Patent Owner”) filed a Preliminary Response to the Petition. Paper 11
`
`(“Prelim. Resp.”).
`
`We have authority under 35 U.S.C. § 314, which provides that an
`
`inter partes review may not be instituted unless there is a reasonable
`
`likelihood that the petitioner would prevail with respect to at least one of the
`
`claims challenged in the petition. 35 U.S.C. § 314(a). Upon considering the
`
`argument and evidence presented in the Petition and Preliminary Response,
`
`we determine that Petitioner has established a reasonable likelihood that it
`
`would prevail in showing the unpatentability of at least one claim challenged
`
`in the Petition. Accordingly, we institute an inter partes review of claims
`
`1–31 of the ’833 patent.
`
`A.
`
`Real Parties-in-Interest
`
`Petitioner identifies Mylan Institutional LLC, Mylan Inc., and Mylan
`
`N.V. as real parties-in-interest. Pet. 1. Patent Owner identifies Novo
`
`Nordisk A/S, Novo Nordisk Inc., Novo Holdings A/S, and Nordisk
`
`Foundation as real parties-in-interest. Paper 6, 1.
`
`B.
`
`Related Proceedings
`
`Petitioner provides notice of a district court litigation involving the
`
`’833 patent: Novo Nordisk Inc. and Novo Nordisk A/S v. Mylan Institutional
`
`LLC, No. 19-cv-01551-CMC (D. Del.). Pet. 1. Petitioner also notes that a
`
`patent application in the same patent family is pending before the Office:
`
`U.S. Patent Application No. 16/260,204, filed on January 29, 2019. Id. at 2.
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`IPR2020-00324
`Patent 8,114,833 B2
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`Patent Owner provides notice of two district court litigations
`
`involving the ’833 patent, explaining that Novo Nordisk Inc. and Novo
`
`Nordisk A/S v. Mylan Institutional LLC, No. 19-cv-01551-CFC (D. Del.) is
`
`currently pending, and that Novo Nordisk Inc. and Novo Nordisk A/S v.
`
`Mylan Institutional LLC, No. 19-cv-164 (N.D.W. Va.) has been voluntarily
`
`dismissed. Paper 6, 1.
`
`C.
`
`The ’833 Patent
`
`The ’833 patent relates to pharmaceutical formulations comprising a
`
`peptide and propylene glycol and methods of preparing such formulations.
`
`Ex. 1001, 1:18–20. The Specification explains that “[t]he inclusion of
`
`isotonicity agents in peptide-containing pharmaceutical formulations is
`
`widely known and one of the more common isotonic agents used in such
`
`formulations is mannitol.” Id. at 1:30–33. According to the Specification,
`
`“the present inventors have observed that mannitol causes problems during
`
`the production of peptide formulations as it crystallizes resulting in deposits
`
`in the production equipment and in the final product.” Id. at 1:33–36.
`
`Because such deposits must be cleaned during production, production
`
`capability may be reduced. Id. at 1:36–39. Additionally, because such
`
`deposits may require vials or cartridges containing the peptide formulation
`
`to be discarded, yield of the final product may be reduced. Id. at 1:39–42.
`
`Further, according to the Specification, the inventors have observed clogging
`
`of injection devices used to administer peptide formulations comprising
`
`mannitol. Id. at 1:42–45.
`
`The Specification explains that “peptide formulations containing
`
`propylene glycol at certain concentrations exhibit reduced deposits in
`
`production equipment and in the final product and also exhibit reduced
`
`clogging of injection devices.” Id. at 1:53–57. The formulations may
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`IPR2020-00324
`Patent 8,114,833 B2
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`comprise “any peptide.” Id. at 1:57–58. In particular, the invention
`
`discloses an embodiment wherein the peptide included in the formulation is
`
`a GLP-1 (glucagon-like peptide-1) agonist, which “is understood to refer to
`
`any peptide which fully or partially activates the human GLP-1 receptor.”
`
`Id. at 4:25–28.
`
`D.
`
`Illustrative Claims
`
`Petitioner challenges claims 1–31 of the ’833 patent. Independent
`
`claims 1, 16, 23, 26, and 29, set forth below, are illustrative.
`
` 1. A pharmaceutical formulation comprising at least one
`GLP-1 agonist, a disodium phosphate dihydrate buffer and
`propylene glycol, wherein said propylene glycol is present in
`said formulation in a final concentration of from about
`1 mg/ml to about 100 mg/ml and wherein said formulation has
`a pH of from about 7.0 to about 10.0.
`
` 16. A method of preparing a GLP-1 agonist formulation
`suitable for use in an injection device, said method compris
`ing preparing a formulation containing a GLP-1 agonist, pro-
`pylene glycol, a disodium phosphate dihydrate buffer, and a
`preservative, wherein said propylene glycol is present in a
`concentration from about 1 mg/ml to about 100 mg/ml, and
`wherein said formulation has a pH from about 7.0 to about
`10.0, and wherein said GLP-1 agonist, said propylene glycol
`and said buffer and preservative are mixed together to pro-
`duce said formulation as follows:
` a) preparing a first solution by dissolving preservative,
` propylene glycol and buffer in water,
` b) preparing a second solution by dissolving the GLP-1
` agonist in water;
` c) mixing the first and second solutions; and
`adjusting the pH of the mixture in c) to a pH of from about 7.0
`to about 10.0.
`
` 23. A method for reducing deposits on production
`equipment during production of a GLP-1 agonist formulation,
`said method comprising replacing the isotonicity agent
`previously utilized in said formulation with propylene glycol at
`
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`IPR2020-00324
`Patent 8,114,833 B2
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`a concentration of between 1-100 mg/ml, and wherein said
`GLP-1 agonist formulation comprises a disodium phosphate
`dihydrate buffer.
` 26. A method for reducing deposits in the final product
`during production of a GLP-1 agonist formulation, said
`method comprising replacing the isotonicity agent previously
`utilized in said formulation with propylene glycol at a con-
`centration of between 1-100 mg/ml, and wherein said GLP-1
`agonist formulation comprises a disodium phosphate dihy-
`drate buffer.
`
` 29. A method for reducing the clogging of injection devices
`by a GLP-1 agonist formulation, said method comprising
`replacing the isotonicity agent previously utilized in said
`formulation with propylene glycol at a concentration of
`between 1-100 mg/ml, and wherein said GLP-1 agonist for
`mulation comprises a disodium phosphate dihydrate buffer.
`
`Ex. 1001, 22:49–54, 23:37–53, 24:7–13, 25–31, 44–49.
`
`E.
`
`Asserted Grounds of Unpatentability
`
`Petitioner asserts that claims 1–31 would have been unpatentable on
`
`the following grounds.
`
`Claims Challenged
`1–15
`
`35 U.S.C. §
`102(b)
`
`Flink1
`
`Reference(s)
`
`1–15
`
`1–31
`
`
`
`103(a)2
`
`Flink
`
`103(a)
`
`Flink, Betz3
`
`
`1 Flink et al., PCT Publication No. WO 03/002136 A2, published
`Jan. 9, 2003 (“Flink,” Ex. 1004).
`2 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29, 125
`Stat. 284, 287–88 (2011), amended 35 U.S.C. § 103, effective March 16,
`2013. Because the application from which the ’833 patent issued was filed
`before this date, the pre-AIA version of § 103 applies.
`3 Betz et al., PCT Publication No. WO 04/004781 A1, published
`Jan. 15, 2004 (“Betz,” Ex. 1005).
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`5
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`IPR2020-00324
`Patent 8,114,833 B2
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`Petitioner also relies on the Declaration of Laird Forrest, Ph.D.
`
`(Ex. 1002).
`
`II. ANALYSIS
`
`A.
`
`Person of Ordinary Skill in the Art
`
`The level of skill in the art is a factual determination that provides a
`
`primary guarantee of objectivity in an obviousness analysis. Al-Site Corp. v.
`
`VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing Graham v. John
`
`Deere Co., 383 U.S. 1, 17–18 (1966); Ryko Mfg. Co. v. Nu-Star, Inc., 950
`
`F.2d 714, 718 (Fed. Cir. 1991)).
`
`Petitioner asserts that a person of ordinary skill in the art at the time of
`
`the invention would have had
`
`(1) a Pharm. D., or a Ph.D. in pharmacy, chemical engineering,
`bioengineering, chemistry, or related discipline; (2) at least two
`years of experience in the area of protein or peptide therapeutic
`development and/or manufacturing; and (3) experience with the
`development, design, manufacture, or formulation of therapeutic
`agents, and the literature concerning protein or peptide
`formulation and design.
`
`Pet. 4 (citing Ex. 1002 ¶¶ 26–27). Patent Owner asserts that it does not
`
`contest Petitioner’s description of the level of ordinary skill in the art in the
`
`Preliminary Response. Prelim. Resp. 17.
`
`At this stage of the proceeding, we adopt Petitioner’s definition as we
`
`find it is consistent with the level of skill in the art at the time of the
`
`invention as reflected by the prior art. See Okajima v. Bourdeau, 261 F.3d
`
`1350, 1355 (Fed. Cir. 2001) (explaining that specific findings regarding
`
`ordinary skill level are not required “where the prior art itself reflects an
`
`appropriate level and a need for testimony is not shown” (quoting Litton
`
`Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir.
`
`1985))).
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`6
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`IPR2020-00324
`Patent 8,114,833 B2
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`B.
`
`Claim Construction
`
`The Board applies the same claim construction standard that would be
`
`used to construe the claim in a civil action under 35 U.S.C. § 282(b). 37
`
`C.F.R. § 100(b) (2019. Under that standard, claim terms “are generally
`
`given their ordinary and customary meaning” as understood by a person of
`
`ordinary skill in the art at the time of the invention. Phillips v. AWH Corp.,
`
`415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc). “In determining the
`
`meaning of the disputed claim limitation, we look principally to the intrinsic
`
`evidence of record, examining the claim language itself, the written
`
`description, and the prosecution history, if in evidence.” DePuy Spine, Inc.
`
`v. Medtronic Sofamor Danek, Inc., 469 F.3d 1005, 1014 (Fed. Cir. 2006)
`
`(citing Phillips, 415 F.3d at 1312–17). Extrinsic evidence is “less significant
`
`than the intrinsic record in determining ‘the legally operative meaning of
`
`claim language.’” Phillips, 415 F.3d at 1317.
`
`Petitioner asserts that “no claim terms currently require construction,
`
`and all terms have their plain meaning.” Pet. 10. Patent Owner agrees that
`
`no claim terms require construction. Prelim. Resp. 17. The parties,
`
`however, dispute whether the preambles of claims 23, 26, 29 should be
`
`construed as non-limiting. Pet. 10; Prelim. Resp. 17–18.
`
`Petitioner asserts that the preambles of those claims should be
`
`construed as non-limiting because they recite statements of purpose and the
`
`inherent intended result of using such a formulation by reciting methods for
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`“reducing deposits on production equipment,” “reducing deposits in the final
`
`product,” and “reducing the clogging of injection devices.” Pet 10–11
`
`(quoting, in part, claims 23, 26, and 29). Petitioner asserts that achieving
`
`such reductions in deposits and clogging are the inherent result of using a
`
`GLP-1 agonist formulation containing propylene glycol as the isotonic
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`7
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`IPR2020-00324
`Patent 8,114,833 B2
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`agent, as recited by the method steps. Id. at 11. Patent Owner does not
`
`explain its contrary position. Prelim. Resp. 17–18.
`
`On this record, we agree with Petitioner that the preambles of claims
`
`23, 26, and 29 are not limiting. The recitation of “reducing deposits on
`
`production equipment,” “reducing deposits in the final product,” and
`
`“reducing the clogging of injection devices” merely state the purpose or
`
`intended use of the claimed subject matter without reciting essential
`
`structure or steps, and have not been shown to be “necessary to give life,
`
`meaning, and vitality” to the claims. See Boehringer Ingelheim Vetmedica,
`
`Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003);
`
`Catalina Mktg. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 808 (Fed.
`
`Cir. 2002).
`
`We agree with the parties that at this stage of the proceeding, express
`
`construction of any remaining claim term is unnecessary for purposes of
`
`rendering this Decision. See Wellman, Inc. v. Eastman Chem. Co., 642 F.3d
`
`1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only be construed ‘to the
`
`extent necessary to resolve the controversy.’”) (quoting Vivid Techs., Inc. v.
`
`Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
`
`C.
`
`Anticipation by Flink
`
`Petitioner asserts that claims 1–15 are anticipated by Flink. Pet. 27–
`
`39. Patent Owner disagrees. Prelim. Resp. 18–35.
`
`1.
`
`Flink
`
`Flink relates to pharmaceutical formulations comprising GLP-1
`
`compounds and methods for making such formulations. Ex. 1004, 2.4 In
`
`
`4 Our citation to the Petitioner’s exhibits, except Exhibit 1001, refers to the
`page numbering added to those references by Petitioner.
`
`8
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`IPR2020-00324
`Patent 8,114,833 B2
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`one aspect, Flink claim 14, which depends from claim 13, which in turn
`
`depends from “any one of claims 1–12,” is directed to a pharmaceutical
`
`formulation comprising an aqueous solution of a GLP-1 compound, a buffer,
`
`a preservative, and an isotonic agent in a concentration from 1mg/ml to
`
`50 mg/ml. See id. at 47–48 (claims 5, 13, and 14). Flink’s independent
`
`claim 5 recites that the GLP-1 compound is “GLP-1(7-37) or an analogue
`
`thereof wherein an amino acid residue of the parent peptide has a lipophilic
`
`substituent attached optionally via a spacer.” Id. at 47. In the examples of
`
`its formulations, Flink refers to “Compound 1” as the GLP-1 agonist, i.e.,
`
`“Arg34, Lys26 (Nε-(γ-Glu(Nα-hexadecanoyl))) GLP-1 (7-37).” Id. at 37.
`
`Flink teaches that in a preferred embodiment of the invention, the
`
`buffer is “glycylglycine, sodium dihydrogen phosphate, disodium hydrogen
`
`phosphate, sodium phosphate or mixtures thereof.” Id. at 18. In Example 7,
`
`Flink discloses a number of formulations comprising Compound 1 and
`
`disodium hydrogenphosphate dihydrate as the buffer. Id. at 45. In those
`
`examples, Flink uses mannitol as the isotonic agent. Id. Flink’s disclosure
`
`explains that the isotonic agent is selected from the group consisting of
`
`a salt (e.g. sodium chloride), a polyhydric alcohol (e.g.
`propyleneglycol, xylitol, mannitol, sorbitol or glycerol), a
`monosaccharide (e.g. glucose or maltose), a disaccharide (e.g.
`sucrose), an amino acid (e.g. L-glycine, L-histidine, arginine,
`lysine,
`isoleucine, aspartic acid,
`tryptophan,
`threonine),
`polyethyleneglycol (e.g. PEG400), or mixtures thereof. In a
`further embodiment of the invention the isotonic agent is selected
`from the group consisting of sodium chloride, glycerol, mannitol,
`glucose, sucrose, L-glycine, L-histidine, arginine, lysine or
`mixtures thereof.
`
`Id. at 19–20. Flink explains that “[e]ach of these specific isotonic agents
`
`constitutes an alternative embodiment of the invention. In a preferred
`
`embodiments [sic] of the invention the isotonic agent is mannitol or
`
`9
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`IPR2020-00324
`Patent 8,114,833 B2
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`glycerol.” Id. at 20. Flink’s claim 5 recites that the formulation has a pH
`
`from 7.0 to 10, and that “if an isotonic agent is present and pH is 7.4 then
`
`mannitol or NaCl is not the isotonic agent.” Id. at 47.
`
`2.
`
`Analysis
`
`“A claim is anticipated only if each and every element as set forth in
`
`the claim is found, either expressly or inherently described, in a single prior
`
`art reference.” Schering Corp. v. Geneva Pharms, 339 F.3d 1373 (Fed. Cir.
`
`2003) (quoting Verdegaal Bros., Inc. v. Union Oil Co. of Cal., 814 F.2d 628,
`
`631 (Fed. Cir. 1987)). It is well settled that “a reference can anticipate a
`
`claim even if it ‘d[oes] not expressly spell out’ all the limitations arranged or
`
`combined as in the claim, if a person of skill in the art, reading the reference,
`
`would ‘at once envisage’ the claimed arrangement or combination.”
`
`Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed.
`
`Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681 (1962)).
`
`Regarding claim 1, Petitioner asserts that Flink discloses each element
`
`of the claim. Pet. 27. In particular, Petitioner directs us to Flink’s
`
`dependent claim 14, and certain claims from which it depends, i.e.,
`
`independent claim 5 and dependent claims 6, 8, 10, 11, 12, and 13. Id. at
`
`28–29. Based on that dependency, Petitioner asserts that Flink’s claim 14
`
`recites a pharmaceutical formulation comprising a “GLP-1 compound . . .
`
`wherein said GLP-1 compound is GLP-1(7-37) or an analogue thereof
`
`wherein an amino acid residue of the parent peptide has a lipophilic
`
`substituent attached optionally via a spacer.” Id. at 29 (quoting Ex. 1004,
`
`47, Flink claim 5). Petitioner and Dr. Forrest assert that one of those
`
`compounds disclosed by Flink is liraglutide, a prior art GLP-1 agonist. Id.
`
`(citing Ex. 1004, 5:13–14, 27:26–27, 37:26–28, 38–46; Ex. 1002 ¶ 151).
`
`10
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`Petitioner asserts that Flink’s claim 14 also requires a buffer and that
`
`Flink discloses disodium phosphate as “one of the small group of acceptable
`
`buffers captured by claim 14,” and indeed as one that is particularly
`
`preferred. Id. at 30 (citing Ex. 1004, 18:27–33; Ex. 1002 ¶¶ 152–153).
`
`Petitioner asserts that a person of ordinary skill in the art would have
`
`understood that this disclosure included the various hydrated forms of the
`
`buffer, including the dihydrate form, as specifically used in Flink’s
`
`Example 7. Id. (citing Ex. 1004, 45–46; Ex. 1002 ¶¶ 154–156).
`
`
`
`Petitioner asserts that Flink’s claim 14 requires an isotonicity agent
`
`and that Flink discloses propylene glycol as one of a small group of isotonic
`
`agents captured by claim 14. Id. at 30 (citing Ex. 1004, 19:34–20:9).
`
`Further, Petitioner asserts that Flink’s claim 14 recites that the isotonic agent
`
`is present in a concentration from 1 mg/ml to 50 mg/ml, which falls within
`
`the range claimed by the challenged claim 1. Id. (citing Ex. 1004, 48:17–18;
`
`Ex. 1002 ¶ 157).
`
`
`
`Petitioner asserts that Flink’s claim 14 also requires the formulation to
`
`have a pH between 7 and 10, as recited by challenged claim 1. Id. at 31
`
`(citing Ex. 1004, 4:17–20, 4:32–5:2, 5:17–6:15, 9:20–10:22; Ex. 1002,
`
`¶ 169). Additionally, Petitioner notes that Flink disclosed several exemplary
`
`formulations having a pH between 7 and 10. Id. (citing Ex. 1004, 27–35,
`
`38–46).
`
`According to Petitioner, “[a]nticipation is not avoided here simply
`
`because [Flink’s] claim 14 discloses buffers and isotonic agents without
`
`expressly stating that disodium phosphate dihydrate was the buffer and
`
`propylene glycol was the isotonic agent.” Id. Petitioner contends that
`
`Flink’s disclosure is sufficient for anticipation because Flink discloses the
`
`complete roadmap to challenged claim 1 by reciting the GLP-1 formulation
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`comprising a buffer and isonticity agent, and providing a disclosure of four
`
`particularly preferred buffers and 18 preferred isotonicity agents. Id. at 33
`
`(citing Wm. Wrigley Jr. Co. v. Cadbury Adams USA, LLC, 683 F.3d 1356
`
`(Fed. Cir. 2012; Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1376
`
`(Fed. Cir. 2005)).
`
`Patent Owner asserts that the scope of Flink’s claim 14 “is impossibly
`
`ambiguous and cannot disclose the formulations of the ’833 patent with
`
`anything approaching the required specificity” for anticipation. Prelim.
`
`Resp. 19. Patent Owner asserts that Petitioner failed to clearly identify the
`
`specific disclosures in Flink that form the basis of its anticipation theory. Id.
`
`at 19–24. Additionally, Patent Owner asserts that “Flink does not disclose
`
`any formulation containing both propylene glycol and disodium phosphate
`
`dihydrate . . . [a]nd it provide no ‘specific guidance’ that could lead one to
`
`such a formulation.” Id. at 26–27.
`
`Regarding the isotonicity agent, Patent Owner asserts that (a) “Flink
`
`puts no special emphasis on isotonic agents and presents their use as
`
`optional,” (b) “[s]ome of the more stable formulations in the reference omit
`
`an isotonic agent altogether,” (c) propylene glycol is not among the nine
`
`isotonic agents Flink discloses as “embodiment[s] of the invention,”
`
`(d) Flink highlights mannitol and glycerol as “preferred” isotonic agents,
`
`(e) the “vast majority of Flink’s formulations use mannitol, the chemical that
`
`causes the problem that the ’833 patent’s inventors solved,” (f) “Flink’s only
`
`mention of propylene glycol” is in a disclosure of a “further embodiment of
`
`the invention,” and (g) Flink “offers no working propylene glycol
`
`formulation and does not provide any guidance that would lead one of
`
`ordinary skill to create one.” Id. at 26–28.
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`12
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`IPR2020-00324
`Patent 8,114,833 B2
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`Regarding the buffer, Patent Owner asserts that (a) disodium
`
`phosphate dihydrate is not among the “twelve chemicals or ‘mixtures
`
`thereof’” that Flink specifically discloses, and (b) Flink’s only disclosure of
`
`disodium phosphate dihydrate is an example formulation “in combination
`
`with mannitol and glycerol, not propylene glycol.” Id. at 28–29. According
`
`to Patent Owner, Petitioner’s anticipation argument is “an attempt to recreate
`
`the ’833 patent’s invention from various, disparate portions of Flink, each
`
`taken out of context—precisely the kind of picking and choosing that the
`
`law forbids in the anticipation analysis.” Id. at 29 (citing Akzo N.V. v. U.S.
`
`Int’l Trade Comm’n, 808 F.2d 1471, 1480 (Fed. Cir. 1986)).
`
`Having considered the evidence and arguments, on this record, we
`
`determine that the Petitioner has demonstrated sufficiently that each
`
`limitation of claim 1 is disclosed by Flink. To begin, Petitioner has shown
`
`that Flink’s claims disclose a pharmaceutical formulation comprising a
`
`GLP-1 compound, a buffer, an isotonic agent present in an amount of
`
`1 mg/ml to 50 mg/ml, wherein the formulation has a pH from 7.0 to 10.
`
`Specifically, Petitioner directs us to Flink’s claim 14 and certain claims from
`
`which it depends, particularly independent claim 5 and dependent claim 13.
`
`Ex. 1004, 47–48. Flink’s claim 14 recites “[t]he formulation according to
`
`claim 13, wherein said isotonic agent is present in a concentration from 1
`
`mg/ml to 50 gm/ml.” Id. at 48. Flink’s claim 13 recites “[t]he formulation
`
`according to any one of claims 1–12, further comprising an isotonic agent.”
`
`Id. Flink’s independent claim 5, i.e., “one of claims 1–12,” discloses the
`
`pharmaceutical formulation comprising an aqueous solution of a GLP-1
`
`compound, a buffer, and, optionally an isotonic agent that may or may not
`
`be mannitol. Id.
`
`13
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`IPR2020-00324
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`With that roadmap in place, Petitioner directs us to disclosures in
`
`Flink that provide guidance regarding the selection of a buffer and an
`
`isotonic agent. Petitioner identifies disodium hydrogen phosphate among
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`Flink’s disclosed buffers for a preferred embodiment, and Flink’s specific
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`use of disodium hydrogenphosphate dihydrate in a number of exemplary
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`formulations. Id. at 30 (citing Ex. 1004, 18:31–33, Example 7); Ex. 1002
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`¶¶ 153–156. As for an isotonic agent, Petitioner directs us to Flink’s
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`teaching that the isotonic agent is selected from a group consisting of agents
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`including propylene glycol. Id. (citing Ex. 1004, 19:34–20:9). As in
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`Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1376 (Fed. Cir. 2005),
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`“the notion that one of these ingredients cannot anticipate because it appears
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`without special emphasis in a longer list” is rejected. Thus, our anticipation
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`analysis is not fueled by “how the prior art characterizes that disclosure or
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`whether alternatives are also disclosed.” Perricone, 432 F.3d at 1376
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`(quoting Hewlet-Packard Co. v. Mustek Sys., Inc., 340 F.3d 1314, 1324 n.6
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`(Fed. Cir. 2003)).
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`We have considered each of Patent Owner’s arguments, but do not
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`find them adequately supported at this stage of the proceeding to deny the
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`Petition. For example, Patent Owner asserts that the Petition fails to clearly
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`identify the specific disclosures in Flink that support its anticipation
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`challenge. However, as we have set forth above, Petitioner has identified the
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`roadmap to the formulation of challenged claim 1 in Flink’s claims 5, 13,
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`and 14, and has further identified the guidance Flink provides for selecting a
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`buffer and isotonic agent. As for Patent Owner’s assertion that Flink does
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`not specifically disclose any formulation containing both propylene glycol
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`and disodium phosphate dihydrate, we agree. However, we disagree with
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`Patent Owner’s assertion that Flink does not provide “‘specific guidance’
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`IPR2020-00324
`Patent 8,114,833 B2
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`that could lead one to such a formulation.” Prelim. Resp. 26–27. As we
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`have discussed above, Flink teaches an artisan which isotonic agents and
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`which buffers may be selected for its formulations—propylene glycol is
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`among the disclosed group of isotonic agents and disodium phosphate
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`dihydrate is among the disclosed buffers (as expressly set forth in Flink’s
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`Example 7).
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`Although Flink exemplifies formulations comprising disodium
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`phosphate dihydrate in combination with mannitol, Patent Owner has not
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`identified, nor do we see, any teaching in Flink that such buffer must be used
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`in combination with mannitol, or that any specific buffer must be used in
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`combination with any specific isotonic agent. Indeed, Flink does not limit
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`which of the disclosed agents and buffers may be selected for use together in
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`a formulation. Further, review of Flink’s independent claim 5 reveals that,
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`in one aspect, the claim recites formulations that expressly do not include
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`mannitol as the isotonic agent. Thus, Flink’s teaching that the isotonic agent
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`is selected from a relatively small group of chemicals along with Flink’s
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`claim language indicating that mannitol will not be selected as the isotonic
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`agent for some of its formulations, provides additional support to find on the
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`present record that a person of skill in the art could at once envisage any of
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`Flink’s exemplary formulations (set forth in Flink’s Example 7) comprising
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`disodium phosphate dihydrate to include another disclosed isotonic agent in
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`place of mannitol, namely propylene glycol.
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`We discount Patent Owner’s assertions that “Flink puts no special
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`emphasis on isotonic agents and presents their use as optional,” and that
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`“[s]ome of the more stable formulations in the reference omit an isotonic
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`agent altogether.” Prelim. Resp. 27. Those assertions wholly disregard
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`Flink’s claim 13 which recites the GLP-1 formulation “further comprising
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`IPR2020-00324
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`an isotonic agent,” and claim 14 which recites “[t]he formulation according
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`to claim 13, wherein said isotonic agent is present in a concentration from 1
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`mg/ml to 50 mg/ml,” both of which are relied upon by Petitioner to show
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`anticipation. Ex. 1004, 48; Pet. 28–29.
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` Nor do we credit Patent Owner’s assertion that case law supports
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`rejecting Petitioner’s anticipation theory at this stage of the proceeding.
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`Prelim. Resp. 30–33. For example, Patent Owner asserts that, as in Complex
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`Innovations, LLC v. AstraZeneca AB, IPR2017-00631, Paper No. 13
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`(P.T.A.B. July 24, 2017), Petitioner’s anticipation argument requires
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`“picking and choosing elements among a catalog of separate parts disclosed
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`by [the reference], relying upon a broad disclosure of value ranges to
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`anticipate specific values recited by the challenged claims, and relying on an
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`unsupported calculation by [Petitioner’s expert].” Prelim. Resp. 30 (quoting
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`Complex Innovations at 12). According to Patent Owner, “[t]he same is true
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`here for Mylan’s anticipation theory, which should be rejected.” Id. Patent
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`Owner, however, does not discuss specifically how it contends Petitioner’s
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`anticipation challenge is comparable to Complex Innovations. In any event,
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`we begin by noting that Complex Innovations has not been designated as
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`precedential by the Board.
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`Insofar as Patent Owner relies upon Complex Innovations to allege
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`that any picking and choosing of elements required for Flink to disclose the
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`claimed invention disqualifies it as an anticipatory reference, we disagree on
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`the record before us. We recognize that for anticipation, “it is not enough
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`that the prior art reference . . . includes multiple, distinct teachings that [an
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`ordinary] artisan might somehow combine to achieve the claimed
`
`invention.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed.
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`Cir. 2008). However, the prohibition from picking, choosing, and
`
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`combining disclosures involves scenarios where those combined disclosures
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`are not directly related to each other by the teachings of the cited reference.
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`See id. (quoting In re Arkley, 455 F.2d 586, 587 (CCPA 1972) (An
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`anticipatory reference “must clearly and unequivocally disclose the claimed
`
`[invention] or direct those skilled in the art to the [invention] without any
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`need for picking, choosing, and combining various disclosures not directly
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`related to each other by the teachings of the cited reference.”)). As
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`discussed above, Petitioner has demonstrated persuasively, for the purpose
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`of institution, that Flink’s disclosures of buffers and isotonic agents that may
`
`be used in its formulations, which expressly include a disodium phosphate
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`dihydrate buffer and propylene glycol as claimed are directly related to its
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`disclosure of a GLP-1 formulations comprising a buffer and an isotonic
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`agent. See Purdue Pharma L.P. v. Epic Pharma, LLC, 811 F.3d 1345,
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`1358–59 (Fed. Cir. 2016) (explaining that a listing of the types of
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`therapeutic compounds contemplated for a formulation, although in a
`
`distinct section of the reference, is still considered to be directly related to
`
`disclosure of the formulation in another section of the reference).
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`Insofar as Patent Owner refers to Complex Innovations to allege that
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`Petitioner’s anticipation challenge relies upon “a broad disclosure of value
`
`ranges to anticipate specific values recited by the challenged claims, and
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`relying on an unsupported calculation by [Petitioner’s expert],” we again
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`disagree on this record. As to the latter, Patent Owner has not directed us to
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`any aspect of Petitioner’s anticipation challenge that relies upon calculations
`
`performed by Dr. Forrest. As to the former, Petitioner relies upon Flink’s
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`disclosure in claim 14 of an isotonic agent being present in a concentration
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`from 1 mg/ml to 50 mg/ml to meet the concentration limitation in challenged
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`claim 1 for propylene glycol “from about 1 mg/ml to about 100 mg/ml.” See
`
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`Pet. 28. As our reviewing court has explained, “[a] prior art reference that
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`discloses an overlapping but different range than the claimed range can be
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`anticipatory, even where the prior art range only partially or slightly
`
`overlaps with the claimed range.” Genentech Inc. v. Hospira, Inc., 946 F.3d
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`1333, 1338 (Fed. Cir. 2020) (citing Ineos USA LLC v. Berry Plastics Corp.,
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`783 F.3d 865, 870–71 (Fed. Cir. 2015)). Petitioner has demonstrated that
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`Flink discloses a concentration for an isotonic agent that partially overlaps
`
`the claimed range. Thus, the issue that remains is whether there is evidence
`
`establishing that “the claimed range is critical to the operability of the
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`claimed invention” to show that the claimed formulation is not anticipated.
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`Ineos, 783 F.3d at 871. We have not been directed by Patent Owner to any
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`such evidence at this stage in the proceeding.
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`Accordingly, having considered the arguments and evidence presented
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`by the parties, we find Petitioner has shown a