throbber
Trials@uspto.gov
`571.272.7822
`
`
`Paper 72
`Entered: November 5, 2020
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`MERCK SHARP & DOHME CORP.,
`Petitioner,
`
`v.
`
`WYETH LLC,
`Patent Owner.
`_______________
`
`IPR2017-00380
`Patent 8,562,999 B2
`_______________
`
`
`Before FRANCISCO C. PRATS, ERICA A. FRANKLIN, and
`SHERIDAN K. SNEDDEN, Administrative Patent Judges.1
`
`FRANKLIN, Administrative Patent Judge.
`
`
`
`JUDGMENT
`Final Decision on Remand
`Determining Claims 1–6, 10, 11, 14, 17, 19, and 20 Unpatentable
`35 U.S.C. §§ 144, 318
`
`
`
`
`
`
`
`
`1 As explained in the Panel Change Order, Administrative Patent Judge
`Francisco C. Prats replaces Administrative Patent Judge Jacqueline T.
`Harlow, who is no longer with the Patent Trial and Appeal Board. See Paper
`63.
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`I. INTRODUCTION
`
`We address this case on remand after a decision by the U.S. Court of
`
`Appeals for the Federal Circuit in Merck Sharp & Dohme Corp. v. Wyeth
`
`LLC, 792 F. App’x 813 (Fed. Cir. 2019) (“Merck”).
`
`As background, Merck Sharp & Dohme Corp. (“Petitioner”) filed a
`
`Petition (Paper 1; “Pet.”) to institute an inter partes review of claims 1–6,
`
`10, 11, 14, and 17–20 of U.S. Patent 8,562,999 B2 (Ex. 1001; “the ’999
`
`patent”). Wyeth LLC (“Patent Owner”) filed a Patent Owner’s Preliminary
`
`Response (Paper 6; “Prelim. Resp.”).
`
`On June 13, 2017, we instituted an inter partes review of all
`
`challenged claims. Paper 9 (“Dec. Inst.”). On September 13, 2017, Patent
`
`Owner filed a Patent Owner Response to the Petition. Paper 16 (“PO
`
`Resp.”). On December 13, 2017, Petitioner filed a Reply to the Patent
`
`Owner Response. Paper 28 (“Reply”).
`
`Petitioner and Patent Owner each filed a Motion to Exclude Evidence.
`
`Papers 34 and 38. Each party filed an Opposition to the other party’s
`
`motion. Papers 43 and 47. Each party filed also a Reply to the other party’s
`
`Opposition. Papers 50 and 55.2 Patent Owner filed Motions for Observation
`
`on Cross-Examination Testimony. Papers 39 and 40. Petitioner filed a
`
`Response to each of Patent Owner’s Motions for Observation. Paper 44 and
`
`45.
`
`
`2 We authorized Patent Owner to file a Revised Reply to Petitioner’s
`Opposition to Patent Owner’s Motion to Exclude Evidence that complied
`with the page limit set forth in 37 C.F.R. § 42.24(c)(2). See Paper 54.
`
` 2
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`On February 27, 2018, the parties presented arguments at an oral
`
`hearing. The hearing transcript has been entered in the record. Paper 56
`
`(“Tr.”). We issued a Final Written Decision, in accordance with 37 C.F.R.
`
`§ 42.73, on June 8, 2018. Paper 59 (“FWD”). In the Final Written Decision,
`
`we determined that Petitioner had shown by a preponderance of the evidence
`
`that claims 1–6, 10, 11, 14, 17, 19, and 20 are unpatentable. See 35 U.S.C.
`
`§ 316(e). Additionally, we determined that Petitioner had not shown by a
`
`preponderance of the evidence that claim 18 is unpatentable. In the Final
`
`Written Decision, we also addressed the parties’ Motions to Exclude
`
`Evidence, as set forth below in Section III. FWD 37–40.
`
`Neither party requested a rehearing of any matter decided in the Final
`
`Written Decision. Petitioner, however, appealed the Final Written Decision
`
`to the United States Court of Appeals for the Federal Circuit, challenging
`
`only our determination that Petitioner had not shown by a preponderance of
`
`the evidence that claim 18 is unpatentable.
`
`On November 26, 2019, the Federal Circuit issued a decision in
`
`Merck vacating and remanding the Final Written Decision for further
`
`proceedings. Merck, 792 F. App’x at 814. The Court entered the Mandate
`
`on January 2, 2020. Mandate, Merck Sharp & Dohme Corp. v. Wyeth LLC,
`
`No. 18-2133 (Fed. Cir. Jan. 2, 2020), ECF No. 71. The Court found that our
`
`findings were insufficient to support a determination that Petitioner failed to
`
`demonstrate a motivation or a reasonable expectation of success for
`
`modifying the prior art to yield the subject matter of dependent claim 18.
`
`Merck, 792 F. App’x at 817. In particular, the Federal Circuit explained that
`
`the Board “did not address the evidence as to whether someone skilled in the
`
`art would have been motivated to combine the 13 serotypes [disclosed in the
`
` 3
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`prior art and recited by claim 18] into a CRM197 conjugate or whether the
`
`potential loss of immunogenicity would have dissuaded someone skilled in
`
`the art from making such a combination.” Id. at 818.
`
`On January 24, 2020, we held a conference call with the parties to
`
`discuss their proposals for a procedure on remand, in view of the Board’s
`
`Standard Operating Procedure 9 (“SOP 9”), App’x 2, “Guidance for Parties
`
`Regarding Remand Procedures.” See Paper 66 (Conduct of the Proceeding
`
`Order). As a result, we authorized each party to file a table highlighting
`
`arguments and evidence of record previously asserted in this proceeding
`
`regarding the challenge to claim 18. Paper 66, 4. We explained that
`
`submission of the table was not an opportunity to incorporate by reference
`
`any additional evidence or arguments to their previous submissions
`
`regarding claim 18. Id. at 5. Thereafter, such briefing was completed. See
`
`Paper 67 (Patent Owner’s Citation Table), Paper 68 (Petitioner’s Citation
`
`Table).
`
`Although the Federal Circuit vacated the Final Written Decision only
`
`with respect to “the Board’s obviousness findings with respect to claim 18,”
`
`this Decision on Remand includes: our previous, unappealed analysis on the
`
`patentability of challenged claims 1–6, 10, 11, 14, 17, 19, and 20; 3 our
`
`previous determination on the parties’ Motions to Exclude Evidence, with
`
`
`3 Patent Owner’s appeal was limited to claim 18 and did not challenge the
`findings or conclusions regarding claims 1–6, 10, 11, 14, 17, 19, and 20.
`Our original analysis of claims 1–6, 10, 11, 14, 17, 19, and 20 is included in
`this Decision on Remand only for completeness and we have not revisited
`those claims here.
`
` 4
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`revised remarks relating to Exhibit 1037; 4 and our further discussion
`
`regarding the challenges to claim 18. In other words, in this Decision on
`
`Remand, we revisit only the challenges to claim 18 and the Motion to
`
`Exclude Exhibit with respect to 1037.
`
`A. Related Proceedings
`
`We issued Final Written Decisions in two additional inter partes
`
`reviews challenging claims of the ’999 patent in IPR2017-00378 and
`
`IPR2017-00390. Petitioner has appealed our Final Written Decision in
`
`IPR2017-00378 and the Federal Circuit has vacated and remanded that
`
`decision for the same reasons involved here. Merck, 792 F. App’x at 813–
`
`819. The Decision on Remand in that case is issued concurrently with the
`
`Decision on Remand in the instant case.
`
`B. The ’999 patent
`
`In some aspects, the ’999 patent relates to formulations comprising an
`
`immunogen in the form of a polysaccharide-protein conjugate, a pH buffered
`
`saline solution, and an aluminum salt. Ex. 1001, 2:62–64, 12:9–15. The
`
`Specification defines the term “polysaccharide” as including “any antigenic
`
`saccharide element (or antigenic unit) commonly used in the immunologic
`
`and bacterial vaccine arts, including, but not limited to, a ‘saccharide’, an
`
`‘oligosaccharide’, a ‘polysaccharide’, a ‘liposaccharide’, a ‘lipo-
`
`oligosaccharide (LOS)’, a ‘lipopolysaccharide (LPS)’, a ‘glycosylate’, a
`
`
`4 Petitioner submits Exhibit 1037 and identifies it as “Ireland EPA
`Memorandum regarding ‘Application for IPC licence from AHP
`Manufacturing B.V. Trading as Wyeth Medica Ireland for the Wyeth
`BioPharma Campus at Grange Castle Reg. No. 652’ (June
`11, 2003).” Pet. viii.; Ex. 1037 (“Ireland EPA Memo”).
`
` 5
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`‘glycoconjugate’ and the like.” Id. at 16:32–38.
`
`In certain embodiments, the compositions further comprise a
`
`surfactant. Id. at 12:65–67. The Specification explains that a suitable
`
`surfactant is one that “stabilizes and inhibits aggregation of an immunogenic
`
`composition described herein.” Id. at 13:9–12. According to the
`
`Specification, in one aspect, the “invention relates to the unexpected and
`
`surprising results that formulating an immunogenic composition with a
`
`surfactant such as TweenTM80 significantly enhances the stability and
`
`inhibits precipitation of an immunogenic composition.” Id. at 10:35–39.
`
`The container means includes, among other items, syringes and vials.
`
`Id. at 3:2–8. The Specification explains that “silicone oil is a necessary
`
`component of plastic syringes, as it serves to lubricate the rubber plunger
`
`and facilitate transfer of the plunger down the syringe barrel.” Id. at 2:31–
`
`34. Additionally, silicone oil is used as a coating for glass vials to minimize
`
`protein adsorption, and as a lubricant. Id. at 2:37–41. According to the
`
`Specification, “[i]t has been suggested in the art, that silicone oil, which
`
`induces protein secondary and tertiary conformational changes, might be
`
`responsible for the aggregation/precipitation seen in certain protein
`
`pharmaceutical preparations.” Id. at 2:17–20 (citation omitted). To address
`
`that issue, the Specification states that the invention “broadly relates to novel
`
`formulations which stabilize and inhibit precipitation of immunogenic
`
`compositions.” Id. at 2:53–55. More specifically, certain embodiments of
`
`the invention relate to formulations that inhibit precipitation of immunogenic
`
`compositions comprised in siliconized container means. Id. at 5:44–50.
`
` 6
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`C. Illustrative Claims
`
`Independent claim 1 and dependent claim 18 of the ’999 patent are
`
`illustrative and reproduced below:
`
`1. A formulation comprising (i) a pH buffered saline
`solution, wherein the buffer has a pKa of about 3.5 to about 7.5,
`(ii) an aluminum salt and (iii) one or more polysaccharide-
`protein conjugates, wherein the formulation is comprised in a
`siliconized container means and inhibits aggregation induced by
`the siliconized container means.
`
`18. The formulation of claim 1, wherein the one or more
`polysaccharide-protein conjugate comprises an S. pneumoniae
`serotype 4 polysaccharide conjugated to a CRM197 polypeptide,
`an S. pneumoniae serotype 6B polysaccharide conjugated to a
`CRM197 polypeptide, an S. pneumoniae serotype 9V
`polysaccharide conjugated to a CRM197 polypeptide, an S.
`pneumoniae serotype 14 polysaccharide conjugated to a
`CRM197 polypeptide, an S. pneumoniae serotype 18C
`polysaccharide conjugated to a CRM197 polypeptide, an S.
`pneumoniae serotype 19F polysaccharide conjugated to a
`CRM197 polypeptide, an S. pneumoniae serotype 23F
`polysaccharide conjugated to a CRM197 polypeptide, an S.
`pneumoniae serotype 1 polysaccharide conjugated to a CRM197
`polypeptide, an S. pneumoniae serotype 3 polysaccharide
`conjugated to a CRM197 polypeptide, an S. pneumoniae
`serotype 5 polysaccharide conjugated to a CRM197 polypeptide,
`an S. pneumoniae serotype 6A polysaccharide conjugated to a
`CRM197 polypeptide, an S. pneumoniae serotype 7F
`polysaccharide conjugated to a CRM197 polypeptide and an S.
`pneumoniae serotype 19A polysaccharide conjugated to a
`CRM197 polypeptide.
`
`Ex. 1001, 31:7–12, 32:24–44.
`
`In addition to claim 18, claims 26, 10, 14, 17, and 19 depend directly
`
`from claim 1. Claim 11 depends from claim 10. Claim 20 depends from
`
` 7
`
`
`
`claim 19.
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`D. The Asserted Grounds of Unpatentability
`
`Petitioner challenges the patentability of the claims as follows:
`
`Claim(s) Challenged
`
`35 U.S.C. §
`
`References
`
`16, 10, 11, 14, 17–20
`
`103(a)
`
`Prevenar5, Chiron6
`
`18
`
`
`
`
`
`103(a)
`
`Prevenar, Chiron, Peña7
`
`Petitioner also relies on the Declarations of Dennis L. Kasper, M.D.
`
`(Ex. 1007), Devendra Kalonia, Ph.D. (Ex. 1009), Christopher Jones, Ph.D.
`
`(Ex. 1119), and Harm HogenEsch, D.V.M., Ph.D. (Ex. 1122). Patent Owner
`
`relies on the Declarations of Paul Dalby Ph.D. (Ex. 2116), Ali Fattom, Ph.D.
`
`(Ex. 2118), Lakshmi Khandke, Ph.D. (Ex. 2119), Garry Morefield, Ph.D.
`
`(Ex. 2121), and James W. Thomson, Ph.D. (Ex. 2124).
`
`II. ANALYSIS
`
`A. Claim Construction
`
`For petitions filed before November 13, 2018—as here—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. § 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136
`
`S. Ct. 2131, 2142 (2016) (affirming applicability of broadest reasonable
`
`construction standard to inter partes review proceedings). Under that
`
`
`5 Summary of Product Characteristics for Prevenar Suspension for injection:
`Pneumococcal saccharide conjugated vaccine, adsorbed, Annex 1:1–15
`(2005). Ex. 1017 (“Prevenar”).
`6 Patent Application Publication No. WO 2003/009869 A1 by Mario
`Contorni et al., published February 6, 2003. Ex. 1011 (“Chiron”).
`7 de la Peña et al., Present and future of the pneumonia vaccination, 24(4)
`PEDIATRIKA 47–55(2004) (English Translation). Ex. 1015 (“Peña”).
`
` 8
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`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, deliberateness, and precision. In re
`
`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`
`Petitioner and Patent Owner propose constructions for certain claims
`
`terms. Pet. 33–38; PO Resp. 12–21. As relevant to this Decision, we
`
`address the following claim terms:
`
`1. “polysaccharide” and “polysaccharide-protein conjugates”
`
`Petitioner asserts that the broadest reasonable interpretation of the
`
`claim term “polysaccharide” is set forth in the Specification. Pet. 33–35. In
`
`particular, the Specification defines “polysaccharide” as including “any
`
`antigenic saccharide element (or antigenic unit) commonly used in the
`
`immunologic and bacterial vaccine arts, including, but not limited to, a
`
`‘saccharide’, an ‘oligosaccharide’, a ‘polysaccharide’, a ‘liposaccharide’, a
`
`‘lipo-oligosaccharide (LOS)’, a ‘lipopolysaccharide (LPS)’, a ‘glycosylate’,
`
`a ‘glycoconjugate’ and the like.” Ex. 1001, 16:32–38. Patent Owner
`
`similarly acknowledges that the term “polysaccharide” is expressly defined
`
`in the Specification. PO Resp. 12.
`
`Petitioner does not propose a separate construction for the claim
`
`phrase “polysaccharide-protein conjugates.” Patent Owner, however, asserts
`
`that the broadest reasonable interpretation of that claim phrase is:
`
`a conjugate resulting from reacting any antigenic saccharide
`element (or antigenic unit) commonly used in the immunologic
`and bacterial vaccine arts, including but not limited to, a
`saccharide,
`an
`oligosaccharide,
`a
`polysaccharide,
`a
`
` 9
`
`
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`liposaccharide, a
`lipooligosaccharide, a
`liposaccharide, a
`glycosylate, a glycoconjugate, and the like with a carrier protein,
`that is amenable to standard conjugation procedures, wherein the
`antigenic
`saccharide element
`retains antigenicity after
`conjugation.
`
`PO Resp. 13 (underlining removed). Patent Owner notes that its proposed
`
`construction is “rooted in the preliminary construction adopted by the
`
`Board,” but adds the requirement that the antigenic saccharide element
`
`retains antigenicity after conjugation. Id.
`
`Patent Owner asserts that “a purpose of the invention is to provide
`
`formulations that preserve the antigenicity of immunogenic formulations.”
`
`Id. at 14. According to Patent Owner, the “inhibition of aggregation/
`
`precipitation” described in the Specification is a “proxy for whether there is
`
`a loss of antigenicity in the formulation.” Id. Patent Owner asserts that it
`
`would be “improper to ignore the properties (i.e., antigenicity) of the
`
`conjugate” when construing the claim. Id. at 13–14 In support of its
`
`proposed construction, Patent Owner identifies various instances in the
`
`Specification wherein the polysaccharide-protein conjugate is referred to as
`
`an “immunogen” or “immunogenic” composition. Id. at 14 (citing, e.g., Ex.
`
`1001, 14:19–23) (“the immunogen (i.e., a polysaccharide-protein
`
`conjugate . . .)”).
`
`Patent Owner draws our attention to the Specification discussion in
`
`the “Background of the Invention” section that “the immunogenic
`
`composition must be active throughout its ‘expected’ shelf life, wherein any
`
`breakdown of the immunogenic composition to an inactive or otherwise
`
`undesired form (e.g., an aggregate) lowers the total concentration of the
`
`product.” Id. (quoting Ex. 1001, 1:41–46). According to Patent Owner and
`
`
`
`10
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`its declarant, Dr. Thomson, a person of skill in the art would have
`
`understood an active polysaccharide-protein conjugate composition to mean
`
`an active immunogenic composition. Id. (citing Ex. 2124 ¶ 39). Patent
`
`Owner asserts that “[f]or an immunogen to be capable of inducing an
`
`immune response in a body, the immunogen must be antigenic.” Id. Patent
`
`Owner asserts that “[a]ntigenicity is a prerequisite for immunogenicity.” Id.
`
`at 15. According to Patent Owner, although immunogenicity is not recited
`
`in the claims, it is related to a property recited in the claims, i.e., that the
`
`formulation “inhibits aggregation induced by the siliconized container
`
`means.” Id. Patent Owner asserts that “silicone-induced aggregation is
`
`assessed by measuring antigenicity to determine the extent of the loss of
`
`antigenicity due to silicone-induced aggregation.” Id. (citing Ex. 1001,
`
`Example 4).
`
`Petitioner asserts that the “Board should reject Patent Owner’s
`
`proposed ‘antigenicity’ limitation for the same reasons it rejected the
`
`importation of an ‘immunogenicity’ requirement” in the Institution Decision,
`
`because Patent Owner refers to “antigenicity” as a “prerequisite for
`
`immunogenicity.” Reply 5–6 (citing PO Resp. 15).
`
`Based on the record as a whole, we determine that the Specification
`
`sets forth with reasonable clarity, deliberateness, and precision the definition
`
`of the term “polysaccharide,” as accurately represented by Petitioner, and
`
`acknowledged by Patent Owner. With respect to the phrase
`
`“polysaccharide-protein conjugates,” the Specification does not provide a
`
`similarly precise definition. However, the Specification generally describes
`
`such conjugates in a manner that is consistent with the plain and ordinary
`
`meaning of the phrase. For example, the Specification explains that
`
`
`
`11
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`polysaccharides are “chemically activated (e.g., via reductive amination) to
`
`make the saccharides capable of reacting with the carrier protein.” Ex. 1001,
`
`17:35–37. The Specification also explains that “[c]arrier proteins should be
`
`amenable to standard conjugation procedures.” Id. at 17:47–50. In
`
`particular, the Specification states, “[t]he chemical activation of the
`
`polysaccharides and subsequent conjugation to the carrier protein (i.e., a
`
`polysaccharide-protein conjugate) are achieved by conventional means.” Id.
`
`at 17:43–45. Moreover, as Patent Owner asserts, the Specification describes
`
`the polysaccharide-protein conjugates as an example of an “immunogenic
`
`composition.” Ex. 1001, 1:29–30.
`
`In light of those Specification descriptions, we determine that the
`
`broadest reasonable construction of the claim phrase “polysaccharide-protein
`
`conjugates” refers to an immunogenic composition resulting from reacting
`
`any antigenic saccharide element (or antigenic unit) commonly used in the
`
`immunologic and bacterial vaccine arts, including, but not limited to, a
`
`saccharide, an oligosaccharide, a polysaccharide, a liposaccharide, a lipo-
`
`oligosaccharide, a lipopolysaccharide, a glycosylate, a glycoconjugate, and
`
`the like with a carrier protein that is amenable to standard conjugation
`
`procedures.
`
`Although we recognize that the claimed invention is directed toward
`
`an immunogenic composition, we also note that the claims do not recite any
`
`specific level of immunogenicity for the composition. The Specification
`
`explains that the invention “broadly relates to novel formulations which
`
`stabilize and inhibit precipitation of immunogenic compositions.” Ex. 1001,
`
`2:53–55. The Specification describes aggregation as an indicator of
`
`physical/thermal stability of the immunogenic composition. Id. at 2:7–8.
`
`
`
`12
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`Breakdown of the composition to an undesired form (e.g., an aggregate)
`
`lowers the total concentration of the product. Id. at 1:43–46.
`
`Insofar as Patent Owner asserts that the claims require “measuring
`
`antigenicity to determine the extent of the loss of antigenicity due to
`
`silicone-induced aggregation,” as in Example 4 of the Specification, PO
`
`Resp. 15, we disagree. Although Example 4 discusses total antigenicity (and
`
`loss), the claims do not require the formulation to retain a particular degree
`
`of immunogenicity. Instead, the claims are directed to a formulation
`
`comprising a polysaccharide-protein conjugate, i.e., an “immunogen,” see,
`
`e.g., Ex. 1001, 14:19–23, wherein the formulation inhibits aggregation8
`
`induced by the siliconized container means. The presence of a
`
`polysaccharide-protein conjugate confers the immunogenic element of the
`
`claim. While performing an immunoassay to measure loss of antigenicity,
`
`as in Example 4, may provide information regarding whether silicone-
`
`induced aggregation has occurred, such an assay is not required to meet the
`
`“protein-polysaccharide conjugate” element of the claim. Moreover, as
`
`explained in each example described in the Specification, the occurrence of
`
`aggregation/precipitation may be detected upon visual inspection. See, e.g.,
`
`Ex. 1001, 27:6–11 (discussing visual inspection for precipitation).
`
`2. “the formulation . . . inhibits aggregation induced by the
` siliconized container means”
`
`Petitioner asserts this claim phrase “recites a property of the
`
`formulation as a whole, without attributing inhibitory effect to any specific
`
`ingredient recited in the claim.” Pet. 37 (citing Ex. 1009 ¶ 95). For
`
`
`8 See Ex. 1001, 12:38–40 (describing interchangeable use of the terms
`“precipitation” and “aggregation”).
`
`
`
`13
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`example, Petitioner asserts that the plain language of the claim does not
`
`require that the aluminum salt inhibits silicone-induced aggregation. Id. at
`
`37–38 (citing Ex. 1009 ¶ 96). According to Petitioner, because independent
`
`claim 1 recites a “formulation” followed by an open-ended term,
`
`“comprising,” any element(s) comprised in the formulation may contribute
`
`the required inhibition, so long as the formulation as a whole “inhibits
`
`aggregation induced by the siliconized container means.” Id.
`
`Patent Owner asserts that this claim phrase means that “the
`
`formulation inhibits antigenicity loss of the polysaccharide component of the
`
`polysaccharide-protein conjugate that can occur as a result of aggregation
`
`induced by the siliconized container.” PO Resp. 16. In support of that
`
`construction, Patent Owner relies again upon the antigenicity assessment
`
`described in Example 4 of the Specification. Id. at 16–19. According to
`
`Patent Owner, although visual inspection is used in the Specification
`
`examples to observe particulates, such inspection did not indicate whether
`
`the polysaccharide components of the vaccine maintained or lost antigenicity
`
`as a result of aggregation. Id. at 18.
`
`Further, Patent Owner asserts that the “broadest reasonable
`
`interpretation of claim 1 should go no further than to read on embodiments
`
`that contain the three recited ingredients in a formulation that meets the
`
`functional property limitation.” Id. at 21. According to Patent Owner, the
`
`functional requirement of inhibiting aggregation induced by the siliconized
`
`container means must be satisfied by “a formulation of the three specifically
`
`recited ingredients [buffered saline solution, aluminum salt, and
`
`polysaccharide-protein conjugate], without any un-recited ingredient(s).” Id.
`
`at 20.
`
`
`
`
`
`14
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`Having considered the arguments and evidence, we agree with
`
`Petitioner’s rationale that claim 1 “recites a property of the formulation as a
`
`whole, without attributing inhibitory effect to any specific ingredient recited
`
`in the claim.” Pet. 37. Further, we agree with Patent Owner that the claim
`
`element “the formulation . . . inhibits aggregation induced by the siliconized
`
`container means” may be interpreted to include an embodiment wherein the
`
`three specific ingredients recited in the claim, i.e., buffered saline solution,
`
`aluminum salt, and polysaccharide-protein conjugate, cause inhibition of
`
`aggregation induced by the siliconized container means. See PO Resp. 19–
`
`20. However, we do not agree with Patent Owner that the broadest
`
`reasonable interpretation ends there. Rather, we determine that by reciting
`
`the formulation using the open-ended term “comprising,” along with
`
`attributing the aggregation inhibition property to “the formulation,” the
`
`broadest reasonable construction also includes formulations comprising
`
`additional, unrecited ingredients, and such additional ingredient(s) may
`
`contribute to the required aggregation inhibition by the formulation. See In
`
`re Baxter, 656 F.2d 679, 686 (CCPA 1981) (use of the term “comprising” in
`
`a preamble of a claim permits inclusion of elements in addition to those
`
`specified in the claims); CIAS, Inc. v. Alliance Gaming Corp., 504 F.3d
`
`1356, 1360 (Fed. Cir. 2007) (“In the patent claim context the term
`
`‘comprising’ is well understood to mean ‘including but not limited to.’”).
`
`Further, we do not determine that the claim phrase requires
`
`maintaining any specific level of antigenicity of the conjugate, as asserted by
`
`Patent Owner, PO Resp. 16–18, for the same reasons discussed above, with
`
`respect to Patent Owner’s similar argument raised in connection with its
`
`proposed construction of the “polysaccharide-protein conjugate” term.
`
`
`
`15
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`
`In view of our analysis, we determine that no additional claim terms
`
`require construction for the purpose of this Decision. See Vivid Techs., Inc.
`
`v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (only terms
`
`which are in controversy need to be construed, and only to the extent
`
`necessary to resolve the controversy).
`
`B. Level 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 either (a) “a Ph.D. degree in the
`
`pharmaceutical sciences, physical chemistry or protein chemistry, at least 2
`
`years of work experience formulating protein-based compositions, and
`
`would have had familiarity or experience with the general components of
`
`bacterial vaccines,” or (b) “a Master’s degree in the pharmaceutical sciences,
`
`physical chemistry or protein chemistry, at least 4 years of work experience
`
`formulating protein-based compositions, and would have had familiarity or
`
`experience with the general components of bacterial vaccines.” Pet. 32
`
`(citing Ex. 1009 ¶ 80).
`
`Patent Owner relies upon its definition of the level of ordinary skill in
`
`the art set forth in the Patent Owner Preliminary Response. PO Resp. 21. In
`
`that filing, Patent Owner disagreed with Petitioner’s definition insofar as it
`
`suggests the field of invention involved protein-based formulations. Prelim.
`
`Resp. 10. According to Patent Owner, a person of ordinary skill in the art at
`
`
`
`16
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`the time of the invention would have had either (a) “a Ph.D. degree in the
`
`pharmaceutical sciences, physical chemistry or protein chemistry, at least
`
`two years of work experience formulating polysaccharide-protein conjugate
`
`immunogenic compositions, and would have had familiarity or experience
`
`with the general components and formulation of bacterial vaccines,” or (b)
`
`“a Master’s degree in the pharmaceutical sciences, physical chemistry or
`
`protein chemistry, at least four years of work experience formulating
`
`polysaccharide-protein conjugate immunogenic compositions, and would
`
`have had familiarity or experience with the general components and
`
`formulation of bacterial vaccines.” Id. at 10–11.
`
`In the Institution Decision, we adopted Patent Owner’s description of
`
`the level of ordinary skill at that stage in the proceeding because it included
`
`a requirement for experience relating to polysaccharide-protein conjugates.
`
`Dec. Inst. 13. Based on the record as a whole, we determine that a declarant
`
`having significant experience relating to protein-silicone oil interactions also
`
`offers useful information relating to the subject matter of the challenged
`
`claims. Thus, we also recognize those having ordinary skill in the art
`
`relating to silicone-induced interactions/aggregation in pharmaceuticals.
`
`Thus, we adopt Patent Owner’s description of one having ordinary
`
`skill in the art of formulating polysaccharide-protein conjugate
`
`immunogenic compositions. Further, we describe one having ordinary skill
`
`in the art of silicone-induced interactions/aggregation in pharmaceuticals as
`
`either (a) a Ph.D. degree in the pharmaceutical sciences, physical chemistry
`
`or protein chemistry, at least two years of work experience involving
`
`researching silicone-induced interactions/aggregation in pharmaceuticals, or
`
`(b) a Master’s degree in the pharmaceutical sciences, physical chemistry or
`
`
`
`17
`
`
`
`

`

`IPR2017-00380
`Patent 8,562,999 B2
`
`protein chemistry, at least four years of work experience involving
`
`researching silicone-induced interactions/aggregation in pharmaceuticals.
`
`We also note that the applied prior art reflects the appropriate level of
`
`skill at the time of the claimed invention. See Okajima v. Bourdeau, 261
`
`F.3d 1350, 1355 (Fed. Cir. 2001). We recognize each of Petitioner’s and
`
`Patent Owner’s declarants as qualified to provide the offered opinions on the
`
`level of skill and the knowledge of a person of ordinary skill in the art at the
`
`time of the invention with respect to formulating polysaccharide-protein
`
`conjugates and/or silicone-induced interactions/aggregation in
`
`pharmaceuticals. The relative weight that we assign such testimony,
`
`however, is subject to additional factors. See, e.g., Office Patent Trial
`
`Practice Guide, 77 Fed. Reg. 48,756, 48,763 (Aug. 14, 2012) (“Opinions
`
`expressed without disclosing the underlying facts or data may be given little
`
`or no weight.”).
`
`Petitioner does not challenge the expertise of any of Patent Owner’s
`
`declarants. Patent Owner, however, asserts that Petitioner’s declarants,
`
`Drs. Kalonia and Kasper, lack “experience in developing polysaccharide-
`
`protein conjugate formulations, and certainly not on a commercial scale.”
`
`PO Resp. 21–22. Regarding Dr. Kalonia, Patent Owner asserts that his
`
`experience is “limited to the aggregation of proteins in formulations on a
`
`laboratory scale.” Id. at 20. However, as described in Dr. Kalonia’s
`
`declaration, such experience involves “significant research experience in
`
`protein-interface, protein-protein, and protein-excipient interactions,
`
`including interactions among protein, silicone oil

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket