Trials@uspto.gov
`571.272.7822
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` Paper No. 9
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` Entered: June 8, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`J KYLE BASS and ERICH SPANGENBERG,
`Petitioner,
`
`v.
`
`FRESENIUS KABI USA, LLC,
`Patent Owner.
`____________
`
`Case IPR2016-00254
`Patent 8,476,010 B2
`____________
`
`
`Before JACQUELINE WRIGHT BONILLA, ZHENYU YANG, and
`TINA E. HULSE, Administrative Patent Judges.
`
`HULSE, Administrative Patent Judge.
`
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
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`IPR2016-00254
`Patent 8,476,010 B2
`
`
`
`INTRODUCTION
`J Kyle Bass and Erich Spangenberg (collectively, “Petitioner”) filed a
`Petition requesting an inter partes review of claims 1, 13–15, 17, 18, 20, and
`24–28 of U.S. Patent No. 8,476,010 B2 (Ex. 1001, “the ’010 patent”).
`Paper 1 (“Pet.”). Fresenius Kabi USA, LLC (“Patent Owner”) filed a
`Preliminary Response to the Petition. Paper 6 (“Prelim. Resp.”).
`We have jurisdiction 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 1 of the
`claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering
`the Petition and Preliminary Response, we determine that Petitioner has
`established a reasonable likelihood that it would prevail in showing the
`unpatentability of claims 1, 13–15, 17, 18, 20, and 24–28. Accordingly, we
`institute an inter partes review of those claims.
`A.
`Related Proceedings
`The parties identify several district court proceedings as relating to the
`’010 patent. Pet. 3; Paper 5, 1–2. None of the proceedings is currently
`pending, and Petitioner is not a party to any of the proceedings. Pet. 5.
`Patent Owner also identifies Case No. IPR2015-00715, which
`challenged the ’010 patent. Paper 5, 2. That proceeding was terminated
`before institution. Dr. Reddy’s Labs., Inc. v. Fresenius Kabi USA, LLC,
`Case IPR2015-00715, Paper 12 (PTAB Apr. 2, 2015).
`B.
`The ’010 Patent
`Propofol (2,6-diisopropylphenol) is a well-known intravenous
`anesthetic agent. Ex. 1001, 1:14–15. The ’010 patent relates to
`pharmaceutical formulations of propofol that are stored in containers having
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`nonreactive, inert closures. Id. at 1:8–10. Propofol is a hydrophobic, water-
`insoluble oil that must be incorporated with solubilizing agents, surfactants,
`or an oil-in-water emulsion. Id. at 1:20–23.
`Propofol compositions have been the subject of several patents. Id. at
`1:26–27. The formulation described in U.S. Patent No. 5,714,520 is sold as
`Diprivan®, which comprises “a sterile, pyrogen-free emulsion containing
`1% (W/v) propofol in 10% (w/v) soybean oil.” Id. at 2:33–36. According to
`the Specification, the inventors recognized that the relatively high volume of
`soybean oil used in prior art formulations apparently protects propofol from
`degradation in a container. Id. at 3:63–66. Thus, the Specification states
`that “at oil contents (and/or propofol solvent contents) lower than about 10%
`(w/v), degradation of propofol has been found to occur if the container
`closure is not inert or non-reactive to propofol.” Id. at 3:66–4:2.
`C.
`Illustrative Claim
`Petitioner challenges claims 1, 13–15, 17, 18, 20, and 24–28 of
`the ’010 patent, of which claim 1 is the only independent claim and is
`reproduced below:
`1. A sterile pharmaceutical composition of propofol in a
`container, comprising:
`a container which includes a closure and a composition in
`the container, and
`the composition in the container comprising from 0.5% to
`10% by weight propofol and from about 0 to about 10%
`by weight solvent propofol,
`where when the composition in the container sealed with the
`closure is agitated at a frequency of 300–400
`cycles/minute for 16 hours at room temperature, the
`composition maintains a propofol concentration (w/v)
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`Patent 8,476,010 B2
`measured by HPLC that is at least 93% of the starting
`concentration (w/v) of the propofol;
`where the closure is selected from the group consisting of
`siliconized bromobutyl rubber, metal, and siliconized
`chlorobutyl rubber.
`D.
`The Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1, 13–15, 17, 18, 20,
`and 24–28 of the ’010 patent on the following grounds:
`
`Reference
`Diprivan PDR1 in view of
`Farinotti2 and van den Heuvel3
`Diprivan PDR in view of
`Farinotti and Lundgren4
`
`Basis
`§ 103
`
`§ 103
`
`Claim(s) challenged
`1, 13–15, 17, 18, 20, and
`24–28
`1, 13–15, 17, 18, 20, and
`24–28
`
`Petitioner also relies on the testimony of Thomas N. Feinberg, Ph.D. Ex.
`1002.
`
`
`ANALYSIS
`Person of Ordinary Skill in the Art
`A.
`Petitioner asserts that a person of ordinary skill in the art would have
`been someone with substantial research or industry experience in
`pharmaceutical drug product development, including experience with sterile
`drugs and their packaging, and having at least a master’s degree or doctorate
`
`
`1 Physicians’ Desk Reference, Product Identification Guide and Product
`Information for Diprivan, 341, 2939–45 (1997) (“Diprivan PDR,” Ex. 1005).
`2 R. Farinotti, Interactions physicochimiques et mode de conservation du
`Diprivan ® [Physio-Chemical Interactions and Storage of Diprivan®], 13
`Ann. Fr. Anesth. Reanim. 453–56 (1994) (Ex. 1006). Citations to Farinotti
`in this Decision are to the certified translation provided as Ex. 1007.
`3 J. G. van den Heuvel, US 5,383,864, issued Jan. 24, 1995 (Ex. 1010).
`4 Lundren et al., WO 00/12043, published Mar. 9, 2000 (Ex. 1031).
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`in a related technical field, such as analytical, physical or organic chemistry,
`chemical engineering, pharmaceutics or related subject matter or having
`equivalent experience in such fields. Pet. 8. Patent Owner largely agrees
`with Petitioner’s definition, with the exception that Patent Owner’s
`definition requires experience with propofol and drug product emulsions,
`emulsion systems and their packaging. Prelim. Resp. 19.
`At this stage of the proceeding, given the claims recite compositions
`of propofol in a container, we adopt the level of ordinary skill set forth by
`Patent Owner and note that the prior art itself also demonstrates the level of
`skill in the art at the time of the invention. See Okajima v. Bourdeau, 261
`F.3d 1350, 1355 (Fed. Cir. 2001) (holding the absence of specific findings
`on “level of skill in the art does not give rise to reversible error ‘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)).
`B.
`Claim Construction
`In an inter partes review, the Board interprets claim terms in an
`unexpired patent according to the broadest reasonable construction in light
`of the specification of the patent in which they appear. 37 C.F.R. § 100(b);
`In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1278–79 (Fed. Cir. 2015),
`cert. granted sub nom. Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 890
`(mem.) (2016). Under that standard, and absent any special definitions, we
`give claim terms their ordinary and customary meaning, as would be
`understood by one of ordinary skill in the art at the time of the invention. In
`re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any
`special definitions for claim terms must be set forth with reasonable clarity,
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`deliberateness, and precision. See In re Paulsen, 30 F.3d 1475, 1480
`(Fed. Cir. 1994).
`At this time, the parties agree on the constructions of the following
`terms:
`
`Term
`“from about 0 to about 10% by
`weight solvent for propofol”
`
`“siliconized”
`
`“inert to propofol”
`
`Proposed Construction
`“from approximately zero to
`approximately 10% solvent by
`weight, a range that includes 10%”
`“surface-treated, coated, or
`manufactured with silicone or one
`or more siloxane polymers”
`“having no significant reactivity to
`propofol”
`
`
`At this stage of the proceeding, we determine that it is unnecessary to
`expressly construe any claim terms for purposes of 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. Obviousness over Diprivan PDR, Farinotti, and van den Heuvel
`Petitioner asserts that claims 1, 13–15, 17, 18, 20, and 24–28 are
`unpatentable as obvious over Diprivan PDR, Farinotti, and van den Heuvel.
`Pet. 22–34. Patent Owner opposes Petitioner’s assertion. Prelim. Resp. 22–
`41. Based on the current record, we determine that Petitioner has
`established a reasonable likelihood that it would prevail in showing claims 1,
`13–15, 17, 18, 20, and 24–28 are unpatentable over the cited art.
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`
`Diprivan PDR (Ex. 1005)
`1.
` Diprivan PDR provides product information regarding Diprivan®.
`Diprivan PDR states propofol is very slightly soluble in water and is
`formulated in a white, oil-in-water emulsion. Ex. 1005, 2939. Diprivan®
`contains 10 mg/ml of propofol and 100 mg/ml of soybean oil (id.) in either a
`50 or 100 mL infusion vial with a rubber stopper (id. at 2945).
`2.
`Farinotti (Ex. 1007)
`Farinotti describes the physiochemical interactions and stability of
`Diprivan®. Farinotti explains that propofol is a phenol, which may oxidize
`in the presence of oxygen into two degradation products. Ex. 1007, 453.
`Farinotti states that “[s]torage in diverse conditions (ampoules, vials) at an
`ambient temperature (25ºC) for three years did not show any changes in the
`characteristics of the drug.” Id. at 454. Farinotti further states that in glass
`vial packaging, Diprivan® has good stability and “a lack of adsorption of
`propofol on the bromobutyl stopper.” Id.
`3.
`van den Heuvel (Ex. 1010)
`van den Heuvel relates to a pre-filled injection device with a liquid
`diazepam formulation. Ex. 1010, 1:8–11. van den Heuvel states that it is an
`object of the invention to provide a device where the diazepam formulation
`“can be stored in prolonged contact with at least one rubber sealing member
`without unacceptable deterioration in quality of said formulation taking
`place.” Id. at 2:40–46. van den Heuvel further states that bromobutyl
`rubber, in contrast with chlorobutyl rubber, does not cause unacceptable
`deterioration in quality after prolonged contact with the diazepam
`formulation. Id. at 2:62–66. van den Heuvel discloses the results of storage
`stability testing of liquid diazepam formulations using different rubber
`stoppers. Id. at 4:53–5:39. The rubber stoppers and glass barrels are pre-
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`treated “in the conventional manner by washing, siliconising and sterilising.”
`Id. at 4:61–64. The barrels are stored at a given temperature for a given
`period of time and then the diazepam concentration is determined by high
`performance liquid chromatography (“HPLC”). Id. at 5:1–4.
`4.
`Analysis
`Regarding claim 1, Petitioner asserts that Diprivan PDR in view of
`Farinotti teaches each limitation of claim 1 except the use of a “siliconized”
`bromobutyl rubber stopper. Pet. 23–25. For example, Petitioner argues that
`Diprivan PDR discloses a composition in a vial with a rubber stopper with
`1% propofol by weight/volume, which is within the 0.5% to 10% range
`claimed. Pet. 23 (citing Ex. 1002 ¶ 13). Petitioner further argues that
`although Diprivan PDR does not specify the type of rubber used for the
`closure, Farinotti teaches that the closures used in Diprivan® were
`bromobutyl rubber stoppers. Pet. 24–25 (citing Ex. 1007, 454). Diprivan
`PDR also states that Diprivan® contains 10% soybean oil, which is within
`the claimed range of “from about 0% to about 10%” for the solvent. Id.
`(citing Ex. 1002 ¶ 13).
`Regarding the “stability limitation,”5 Petitioner argues that this
`limitation is an inherent property of Diprivan® that the patentee of the ’010
`patent has observed and confirmed through testing. Pet. 23–24 (citing Ex.
`1002 ¶¶ 15–16). For instance, Example 34 of the ’010 patent discloses the
`
`
`5 For ease of reference, we refer to the limitation “where when the
`composition in the container sealed with the closure is agitated at a
`frequency of 300–400 cycles/minute for 16 hours at room temperature, the
`composition maintains a propofol concentration (w/v) measured by HPLC
`that is at least 93% of the starting concentration (w/v) of the propofol” as
`“the stability limitation.”
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`testing of various propofol compositions, including Diprivan®, with rubber
`closures, as it affects propofol degradation or potency. Ex. 1001, 25:10–45;
`see also id. at 23:21–23. The testing method involves agitating vials of
`propofol at a frequency of 300–400 cycles/minute at room temperature for
`16 hours and comparing HPLC assay results of the samples before and after
`testing to determine if there is a loss in potency or concentration of propofol
`in the formulations, as required by claim 1. Id. at 23:29–34. Example 34
`discloses that 99.3% of the propofol in Diprivan® remained after the
`stability testing. Id. at 25:31. Petitioner and Dr. Feinberg also note that this
`is consistent with the Specification’s statement that prior art formulations
`containing 10% soybean oil, like Diprivan®, are protected from propofol
`degradation. Pet. 24 (citing Ex. 1001, 27:4–7, 3:63–66); Ex. 1002 ¶ 15.
`As for the use of a “siliconized” bromobutyl rubber stopper, Petitioner
`asserts that van den Heuvel discloses siliconized bromobutyl rubber stoppers
`that supports a stable solution over time. Pet. 25–26 (citing Ex. 1010, 4:61–
`5:1, Table A and Table B). Petitioner further asserts that a person of
`ordinary skill in the art would have had a reason to substitute a siliconized
`bromobutyl rubber stopper of van den Heuvel for the bromobutyl rubber
`stopper of Diprivan® because van den Heuvel states a desire to develop a
`pharmaceutical composition that can be stored in prolonged contact with at
`least one rubber sealing member “without unacceptable deterioration in
`quality.” Pet. 26 (citing Ex. 1010, 2:43–46). Dr. Feinberg explains that the
`siliconized bromobutyl rubber closures fulfilled that desire by providing an
`inert sealing member that did not react with the pharmaceutical composition.
`Ex. 1002 ¶ 18. Petitioner further asserts that the known advantages of using
`siliconized rubber closures, such as improved machinability, processing
`efficiencies, and ease of insertion or lubricity, would have further motivated
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`an ordinary artisan to use a siliconized bromobutyl rubber stopper with a
`reasonable expectation of success. Pet. 26–27 (citing Ex. 1002 ¶¶ 20, 21,
`23; Ex. 1004, S4).
`At this stage of the proceeding, we are persuaded that Petitioner has
`established a reasonable likelihood that it would prevail in showing that
`claim 1 is unpatentable over the cited art. That is, we are persuaded that
`Diprivan PDR in view of Farinotti teaches each limitation of claim 1 except
`the use of a siliconized bromobutyl rubber stopper. We are not, however,
`persuaded that an ordinary artisan reading van den Heuvel would conclude
`that it was the siliconization of the bromobutyl rubber stoppers that imparts a
`stable solution of diazepam, as Petitioner appears to assert. See Pet. 26
`(citing Ex. 1010, col. 5, Table A and Table B). Rather, van den Heuvel only
`concludes that “chlorobutyl stoppers cause a considerably larger decrease of
`the diazepam content than the stoppers manufactured from . . . bromobutyl
`rubber.” Ex. 1010, 5:34–37. Because both the chlorobutyl stoppers and the
`bromobutyl stoppers were siliconized, and van den Heuvel does not compare
`the use of siliconized stoppers to unsiliconized stoppers, the results of Tables
`A and B suggest nothing about the effect of siliconizing the stoppers on the
`stability of the formulation. Nevertheless, we are persuaded sufficiently that
`an ordinary artisan, knowing other advantages of siliconizing rubber
`closures, such as ease or efficiency during manufacture, would have had a
`reason to siliconize the bromobutyl rubber closure of Diprivan® with a
`reasonable expectation of success. See Ex. 1002 ¶¶ 20–24; Ex. 1004, S4.
`We also have considered Patent Owner’s arguments in its Preliminary
`Response, but we are not persuaded, on this record, that Petitioner has not
`made the requisite showing in light of those arguments. For example, Patent
`Owner argues that a person of ordinary skill in the art would not be
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`motivated to siliconize the Diprivan® stopper to prevent the loss of propofol
`because there was no evidence that this was a concern at the time of the
`invention. Prelim. Resp. 24–25. On the contrary, argues Patent Owner,
`“silicone oil contamination was a known issue when Diprivan® or any oil-
`in-water emulsion was used with siliconized pharmaceutical closures.” Id.
`at 25. Patent Owner continues, stating the contamination risk would have
`taught away from siliconization. Id. On the current record, we are not
`persuaded. Patent Owner cites several references to argue that stripping of
`silicone “could result” from siliconized rubber closures and that this
`“potential problem” was well known in the art. Id. at 7–8 (citing Ex. 1004,
`S11). Patent Owner further argues that the prior art identifies concerns with
`using silicone with propofol and similar oil-in-water emulsions. Id. at 8, 26–
`27. But the references cited refer to silicone-lubricated syringes, and not to
`siliconized rubber stoppers. See, e.g., Ex. 2006, 501 (stating “propofol strips
`the silicone lubricant from the inside barrel of plastic syringes”); Ex. 2005,
`41 (stating silicone oil is sprayed into the syringes by the manufacturers). At
`this stage of the proceeding, we are not persuaded that an ordinary artisan
`would have been discouraged from using siliconized closures (i.e., stoppers)
`due to potential problems identified in the art or due to results of studies
`using silicone on parts of the container other than the rubber stopper. In re
`Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994) (“A reference may be said to
`teach away when a person of ordinary skill, upon reading the reference,
`would be discouraged from following the path set out in the reference, or
`would be led in a direction divergent from the path that was taken by the
`applicant.”).
`Patent Owner also argues that Petitioner provides no evidence that the
`manufacturers of Diprivan® experienced any problems with its uncoated
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`stoppers to support its argument that manufacturing issues with uncoated
`stoppers would have motivated an ordinary artisan to siliconize Diprivan®
`stoppers. Prelim. Resp. 25–26. At this stage of the proceeding, however, we
`are persuaded that Petitioner has shown sufficiently that an ordinary artisan
`would have recognized the general benefits of siliconizing rubber stoppers,
`which would motivate an ordinary artisan to siliconize the rubber stopper of
`Diprivan®. See Ex. 1002 ¶¶ 20–24; Ex. 1004, S4. As the Supreme Court
`has taught us, “when a work is available in one field of endeavor, design
`incentives and other market forces can prompt variations of it, either in the
`same field or a different one. If a person of ordinary skill can implement a
`predictable variation, § 103 likely bars its patentability.” KSR Int’l Co. v.
`Teleflex Inc., 550 U.S. 398, 417 (2007). Moreover, “precise teachings
`directed to the specific subject matter of the challenged claim” are not
`necessary, as we can take account of the “inferences and creative steps that a
`person of ordinary skill in the art would employ.” Id. at 418.
`Patent Owner further argues that an ordinary artisan would not have
`had a reasonable expectation of success because van den Heuvel describes
`an aqueous solution containing diazepam, which says nothing regarding the
`efficacy of a siliconized bromobutyl stopper with propofol, a hydrophobic
`drug in an oil-in-water emulsion. Prelim. Resp. 29–30. On this record,
`however, we are persuaded that Petitioner has shown sufficiently that an
`ordinary artisan would have had a reasonable expectation of success
`regarding the efficacy of siliconizing the bromobutyl rubber stopper of
`Diprivan® in light of the already stable nature of Diprivan® with an
`uncoated rubber stopper and the generally inert nature of silicone. Pet. 27–
`28 (citing Ex. 1002 ¶ 23; Ex. 1013, 66, 69; Ex. 1001, 9:43–36); see also Ex.
`1001, 25:31 (disclosing 99.3% recovery of propofol after stability testing).
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`As for the dependent claims, we have considered the arguments and
`evidence and find that Petitioner has shown a reasonable likelihood that it
`would prevail as to claims 13–15, 17, 18, 20, and 24–28. Although Patent
`Owner contests the unpatentability of each of those claims (Prelim. Resp.
`36–41), at this stage of the proceeding, we are not persuaded.
`Claims 13–15 require that the solvent be a water-immiscible solvent
`that includes soybean oil. Claims 17 and 20 require that the closure of claim
`1 be coated with a material that is inert to propofol and that it comprise
`siliconized bromobutyl rubber, respectively. Patent Owner argues that van
`den Heuvel discloses none of these properties because the diazepam solution
`does not contain a water-immiscible solvent or a siliconized bromobutyl
`stopper that is inert to propofol. At this stage of the proceeding, we are not
`persuaded because in an obviousness analysis, we look to what the prior art
`teaches as a whole, and not van den Heuvel in isolation, as Patent Owner
`argues here. See In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986)
`(“Non-obviousness cannot be established by attacking references
`individually where the rejection is based upon the teachings of a
`combination of references. Thus, [the prior art reference] must be read, not
`in isolation, but for what it fairly teaches in combination with the prior art as
`a whole.”). On this record, Petitioner has persuaded us sufficiently that the
`combination of Diprivan PDR and Farinotti, together with the knowledge in
`the art regarding the inert nature of silicone, teaches the limitations that
`Patent Owner argues are missing from van den Heuvel.
`Claim 18 requires that the closure “consists essentially of a material
`that is itself inert to propofol.” Petitioner asserts that siliconized bromobutyl
`rubber is inert to propofol. Pet. 31. Patent Owner argues that the claims
`require that the closure consists essentially of a material that is itself inert to
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`propofol, and that bromobutyl rubber is not inert to propofol. Prelim. Resp.
`37–38. Patent Owner appears to argue that the “material” recited in claim
`18 does not include the silicone coating, as opposed to the coating “material”
`in claim 17. Id. On this record, however, we are not persuaded that claim
`18 is so limited, i.e., that a closure “coated with a material inert to propofol”
`may not also be “consist[ing] essentially of a material that is itself inert to
`propofol,” as recited in claim 18. Claim 1 recites that the closure is selected
`from, for example, “siliconized bromobutyl rubber,” which suggests that the
`material of the closure includes the silicone coating. Thus, on the record
`before us, we persuaded that Petitioner has shown sufficiently at this stage of
`the proceeding that claim 18 is unpatentable over the cited references.
`Claims 24–28 recite various stability requirements for the
`pharmaceutical composition in a container according to claim 1. Petitioner
`argues that by including 10% soybean oil, as taught in the cited art, the
`stopper would be non-reactive regardless of the closure selected, and,
`therefore, the composition suggested by the art necessarily would have had
`the stability features recited in challenged claims 24–28. Pet. 32–33. Patent
`Owner argues that Petitioner provides no support for the proposition that
`siliconized rubber stoppers are necessarily at least as good as nonsiliconized
`rubber stoppers in relation to stability features, and, therefore, satisfy the
`claim limitations. Prelim. Resp. 38–41. As support, Patent Owner notes
`that Examples 32 and 33 in the Specification of the ’010 patent show
`considerable variation in loss-prevention properties between different
`siliconization treatments, including some that would not satisfy the claims.
`Id. at 40.
`On this record, however, we are not persuaded. Examples 32 and 33
`do not test formulations with 10% soybean oil, which, as the Specification
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`admits, protects the formulation from degradation. Ex. 1001, 23:61–25:8.
`Because the claims encompass propofol formulations with 10% soybean oil,
`and Diprivan PDR teaches that Diprivan® comprises 10% soybean oil (Ex.
`1005, 2939; Ex. 1002 ¶ 13), at this stage of the proceeding, we are persuaded
`that an ordinary artisan would have had a reasonable expectation that
`siliconizing the bromobutyl stopper of Diprivan® would not have resulted in
`further degradation of the propofol formulation than the unsiliconized
`bromobutyl stopper. See Ex. 1002 ¶¶ 23–24. Accordingly, we are
`persuaded that Petitioner has shown sufficiently at this stage of the
`proceeding that claims 24–28 are unpatentable as obvious over the cited
`prior art.
`D. Obviousness over Diprivan PDR, Farinotti, and Lundgren
`Petitioner asserts that claims 1, 13–15, 17, 18, 20, and 24–28 are
`unpatentable as obvious over Diprivan PDR, Farinotti, and Lundgren.
`Pet. 34–38. Patent Owner opposes Petitioner’s assertion. Prelim. Resp. 41–
`45. We incorporate here our earlier findings and discussion regarding the
`disclosures of Diprivan PDR and Farinotti. Based on the current record, we
`determine that Petitioner has established a reasonable likelihood that it
`would prevail in showing claims 1, 13–15, 17, 18, 20, and 24–28 are
`unpatentable over the cited art.
`1.
`Lundgren (Ex. 1031)
`Lundgren relates to solutions of low molecular weight thrombin
`inhibitors stored in primary packages containing rubber components, such as
`vials, bottles, cartridges, and prefilled syringes. Ex. 1031, 1:5–7. In
`particular, Lundgren states that it has “surprisingly been found that by using
`rubber material containing bromobutyl instead of chlorobutyl, the stability of
`the low molecular weight thrombin inhibitors in solution can be
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`Patent 8,476,010 B2
`considerably improved.” Id. at 1:21–23. Lundgren also discloses the use of
`both unsiliconized and siliconized stoppers, including the use of a
`siliconized bromobutyl rubber closure. Id. at 11:1–13:11.
`2.
`Analysis
`Petitioner’s arguments with respect to this ground are largely the same
`as above, with the exception that Petitioner relies on Lundgren instead of
`van den Heuvel for its disclosure of a siliconized bromobutyl rubber stopper.
`Pet. 35 (citing Ex. 1031, Abstract, 10:13–19, 28–30, 11:1–3). Petitioner also
`asserts that Lundgren “taught that the siliconized bromobutyl rubber closure
`imparted greater stability to the pharmaceutical composition than did
`unsiliconized bromobutyl rubber closures.” Id. (citing Ex. 1031, 11–12).
`Finally, Petitioner asserts that the motivation to combine Diprivan PDR,
`Farinotti, and Lundgren “is essentially the same as that presented for Ground
`1.” Pet. 36.
`For the same reasons stated above, we are persuaded that Petitioner
`has shown a reasonable likelihood that it would prevail in its assertion that
`claims 1, 13–15, 17, 18, 20, and 24–28 are unpatentable over the cited prior
`art. That is, as above, we are persuaded that the combination of Diprivan
`PDR and Farinotti teach each limitation of the claims except the siliconized
`bromobutyl rubber closure. And, as above, we are persuaded that an
`ordinary artisan would have had a reason to siliconize the rubber stopper of
`Diprivan® given the known benefits of doing so.6
`
`
`6 We note, however, that we agree with Patent Owner and are not persuaded
`that Lundgren teaches that “the siliconized bromobutyl rubber closure
`imparted greater stability to the pharmaceutical composition than did
`unsiliconized bromobutyl rubber closures,” as Petitioner asserts. See Pet.
`35. Based on the results cited by Petitioner, Lundgren concluded that
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`Patent Owner makes largely the same arguments as above in
`opposition to this ground. For the same reasons stated above, we are not
`persuaded at this stage of the proceeding that Petitioner has not shown a
`reasonable likelihood of prevailing in its assertion that the claims are
`unpatentable over the cited prior art.
`E.
`Patent Owner’s Remaining Arguments
`1.
`Redundancy
`Patent Owner argues that we should deny the Petition on at least one
`ground because the two grounds are redundant. Prelim. Resp. 45–48.
`Specifically, Patent Owner asserts that Petitioner relies on van den Heuvel
`and Lundgren in the two grounds for the same disclosure and has failed to
`distinguish between the two references. Id. at 46–48. Although we agree
`with Patent Owner that Petitioner relies on van den Heuvel and Lundgren for
`the same disclosure (i.e., siliconized bromobutyl rubber stoppers), Petitioner
`asserts only two grounds, with each ground differing only by a single
`reference. Thus, we determine that, under the circumstances of this case,
`proceeding with both grounds would not be unduly burdensome or contrary
`to our ability to timely complete the instituted proceedings.
`2.
` 35 U.S.C. § 325(d)
`Under 35 U.S.C. § 325(d), the Board may reject a petition because
`“the same or substantially the same prior art or arguments previously were
`presented to the Office.” Id. Patent Owner argues that Petitioner relies on
`
`
`“[m]elagatran in water solution of NaCl exhibits a somewhat lower
`degradation compared to melagatran in water solution of HPβCD.”
`Ex. 1031, 13. Thus, Lundgren says nothing about the stability imparted by
`siliconized versus unsiliconized closures, particularly in light of the fact that
`some of the results of unsiliconized stoppers (e.g., Sample E2) were the
`same as that of the siliconized stoppers (e.g., Sample F2). Id. at 12.
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`the same art and arguments presented during prosecution of the ’010 patent
`application. Prelim. Resp. 49–53. We agree with Patent Owner that
`Diprivan PDR (and its disclosure of Diprivan®), Farinotti, and Lundgren
`(through its U.S. equivalent) were before the examiner during prosecution.
`But Patent Owner has not pointed us to where, during prosecution, the
`examiner raised the known benefits of siliconizing rubber stoppers as a
`reason for a person of ordinary skill in the art to siliconize the bromobutyl
`rubber stopper of Diprivan®, as Petitioner asserts here. Accordingly, we do
`not find that the Petition presents the same arguments previously presented
`to the Office, and we decline to exercise our discretion to deny the Petition
`under § 325(d).
`
`Real Parties-in-Interest
`3.
`Patent Owner asserts that we should deny the Petition because it fails
`to name all the real parties-in-interest. Prelim. Resp. 53–56. In particular,
`Patent Owner argues that because Messrs. Bass and Spangenberg have filed
`petitions for inter partes review through a variety of corporate entities,
`including several “Coalition for Affordable Drugs” entities, the failure to
`identify those organizations here “strongly suggests that Petitioners have
`failed to meet its burden to properly name the real parties-in-interest to this
`case.” Id. at 55. We are not persuaded. Patent Owner’s assertion that the
`other entities “could have an interest using the results of this proceeding as
`part