throbber
UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`EnviroLogix Inc.,
`Petitioner
`
`v.
`
`Ionian Technologies, Inc.,
`Patent Owner.
`
`
`Case IPR2018-00405
`Patent 9,562,263
`
`
`
`MOTION FOR REQUEST FOR RECONSIDERATION
`
`
`
`
`
`
`
`
`
`
`
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`

`

`
`
`Motion for Request for Reconsideration
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`Patent No. 9,562,263
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`
`
`I. 
`II. 
`
`TABLE OF CONTENTS
`
`INTRODUCTION .......................................................................................... 1 
`ARGUMENT .................................................................................................. 4 
`The Board’s conclusion that “side products” would render a
`A. 
`target product undetectable results from a misapprehension of
`Ehses’s disclosure................................................................................. 4 
`The Board also misapprehended and overlooked the arguments
`set forth in the Petition and disclosures in Ehses showing that
`the reaction protocol relied on by Petitioner inherently detects
`product within 10 minutes .................................................................... 7 
`The Board’s misapprehensions were due to incorrect statements
`made in the POPR .............................................................................. 13 
`The Board did not follow Rule 42.108 ............................................... 14 
`D. 
`III.  CONCLUSION ............................................................................................. 15 
`CERTIFICATE OF SERVICE ............................................................................... 17 
`
`B. 
`
`C. 
`
`ii
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`

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`Patent No. 9,562,263
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` Motion for Request for Reconsideration
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`I.
`
`INTRODUCTION
`EnviroLogix Inc. (“Petitioner”) requests reconsideration (rehearing) under
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`§ 42.71(d) of the institution decision issued July 30, 2018 (the “Decision”) in the
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`above-identified matter. The Board’s Decision misapprehended Petitioner’s
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`argument and the corresponding disclosures in Petitioner’s prior art relative to two
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`claim limitations.
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`Specifically, the Board misapprehended the prior art’s disclosures in its
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`analysis of the (a) “omitting a thermal denaturation” step (the “omitting step”) and
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`(b) the “detecting the amplified product within 10 minutes after subjecting the
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`reaction mixture to essentially isothermal conditions” step (the “detecting step”).
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`(Decision at 10.)
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`The prior art expressly discloses omitting thermal denaturation. (Petition at
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`17 (citing Ex. 1002-Ehses at 177-¶3); Ex. 1008-Edwards at ¶¶71-72.) The Board
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`agrees with Petitioner on this point. (See Decision at 11 (“Ehses teaches such a step
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`may be omitted.”)) However, the Board “agree[d] with the Patent Owner that there
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`is insufficient evidence . . . to show that a target product would be detectable when
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`the thermal denaturation step is omitted[.]” (Id.) As discussed in detail below, this
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`finding appears to be based on a misapprehension of Ehses’s disclosures regarding
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`target product detection. (Id. at 10-11.) The Board misapprehends the evidence by
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`focusing on disclosures identified in the Preliminary Patent Owner Response
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`Patent No. 9,562,263
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`(“POPR”), which are not relevant to detecting a target product in real time within 10
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`Motion for Request for Reconsideration
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`
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`minutes under isothermal conditions. Instead, the evidence discussed in the POPR
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`relates to Ehses detecting a target product using “staining.” (See Decision at 10-11.)
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`This evidence is not relevant to detection in real time because staining does not
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`detect a target product in real time, but is a form of end-point detection. In other
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`words, staining detects product after the amplification reaction has concluded. (See
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`Ex. 1002-Ehses at 176, lines 1-2 (“The reaction was stopped by addition of
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`stop/loading dye . . .”).) Once a reaction has been stopped, the target product is no
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`longer being detected in real time.
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`Moreover, the Board misapprehended Petitioner’s argument regarding the
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`detecting step occurring under isothermal conditions. (Decision at 10.) The
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`evidence cited by Patent Owner relating to staining is not relevant to detection that
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`occurs under isothermal conditions because prior to staining the target product
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`undergoes thermal denaturation. (See Ex. 1002-Ehses at 176, lines 2-3 (“…and
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`products were denatured at 95ºC for 10 min. Analysis was performed as described
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`above.”).)
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`Likewise, and at Patent Owner’s invitation to do so per arguments presented
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`in the POPR, the Board misapprehended Petitioner’s arguments regarding whether
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`a target product would be detectable within 10 minutes. Petitioner’s argument is
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`based on inherency, and relates to detection of product as it occurs in real time during
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`Patent No. 9,562,263
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`isothermal incubation. (Petition at 22.) This type of detection is expressly disclosed
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`Motion for Request for Reconsideration
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`
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`in the prior art—all that is missing from the disclosure of Ehses is an express
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`statement that the amplified product is, in fact, detected “within 10 minutes.”
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`Importantly, because Ehses monitors the formation of amplified product in real time,
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`the product is necessarily detected as it accumulates.
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`The issue of whether the prior art inherently discloses the detecting step is at
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`least a disputed issue of material fact. In the POPR, Patent Owner did not present
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`any expert testimony to show that it is not inherently disclosed. The Petition and the
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`supporting declaration of Dr. Edwards show otherwise. At this stage and for
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`purposes of institution, such disputed issues of material fact must be resolved in
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`Petitioner’s favor under § 42.108. The Board overlooked this rule and credited
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`Patent Owner’s attorney argument about unrelated types of “detection.”
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`Finally, the Board misapprehended the legal standard for analyzing
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`anticipation by relying on the alleged “undesirability” of omitting an initial
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`denaturation step from Ehses’s protocol. Specifically, Patent Owner argued that
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`Ehses teaches that omitting a denaturation step undesirably results in side reactions.
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`However, obviousness concepts including “undesirability” and “teaching away” are
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`not relevant to Petitioner’s anticipation argument regarding Ehses.
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`For the reasons identified above and explained in detail below, Petitioner
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`requests reconsideration under § 42.71(d).
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`3
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`Patent No. 9,562,263
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`II. ARGUMENT
`Under § 42.71(d), “[a] party dissatisfied with a decision may file a single
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`Motion for Request for Reconsideration
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`request for rehearing without prior authorization from the Board … The request must
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`specifically identify all matters the party believes the Board misapprehended or
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`overlooked, and the place where each matter was previously addressed in a motion,
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`an opposition, or a reply.” As shown below, the Board misapprehended Petitioner’s
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`argument regarding two claim terms, labeled in the Introduction above as the
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`omitting step and the detecting step.
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`A.
`
`The Board’s conclusion that “side products” would render a target
`product undetectable results from a misapprehension of Ehses’s
`disclosure
`As the Board acknowledged, Ehses discloses an amplification reaction that
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`omits a thermal denaturation step, which meets the claim limitation “without first
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`subjecting the target nucleic acid to a thermal denaturation step associated with
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`amplification of the target polynucleotide sequence[.]” (Petition at 17-18; Decision
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`at 4 (listing the claimed steps) & 11 (“Ehses teaches such a step may be omitted”).)
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`In the POPR, Patent Owner argued that Ehses teaches that omitting such a step is
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`not desirable, because doing so has a tendency to result in side reactions. (Decision
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`at 10 (citing POPR at 6).) Relying on the Patent Owner’s representations in the
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`POPR, the Board concluded that the presence of such “side-reactions result in DNA
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`product that is not detectable, for example with staining. See Ex. 1002, FIG 3C.”
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`4
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`Patent No. 9,562,263
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`(Decision at 10.) However, the reaction analyzed in FIG. 3C is so unrelated to the
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`Motion for Request for Reconsideration
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`embodiment of Ehses relied on by Petitioner that FIG. 3C is irrelevant to the question
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`of whether a detectable product would be detected in real time within 10 minutes
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`when a heat denaturation step is omitted (“Omitted Step Reaction”). These
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`differences are summarized in Table 1 and detailed below.
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`Ehses’s Omitted Step Reaction
`Omits a thermal denaturation step
`15 minute incubation time
`Real time detection
`Product detected under isothermal
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`conditions
`
`TABLE 1
`Reaction analyzed in FIG. 3C
`Includes a thermal denaturation step
`90 minute incubation time
`Endpoint detection
`Product denatured at 95ºC prior to
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`detection
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`As indicated above in Table 1, FIG. 3C analyzes a DNA product that results
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`from a reaction that includes a thermal denaturation step, whereas the reaction
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`described by Ehses and relied on by Petitioner does not include a thermal
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`denaturation step. (Petition at 14.) The reaction shown in FIG. 3C is incubated for
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`90 minutes prior to detection by staining, whereas the Omitted Step Reaction of
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`Ehses may be incubated for as little as 15 minutes and target product accumulation
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`is monitored in real time during the reaction. (Petition at 21.) Petitioner’s expert,
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`Dr. Edwards, explained:
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`Patent No. 9,562,263
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`Motion for Request for Reconsideration
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`“Ehses discloses detecting the amplification of target nucleic acid in
`real time. Ehses states: ‘Upon addition of the enzymes, the
`amplification mixture was incubated 15–60 min in an ICycler
`(BioRAD) and the increase in fluorescence intensity was monitored.’
`Ehses, p. 175, ¶¶ 1, 3. Dyes that bind DNA, like TO-PRO-1, generate
`a fluorescent signal upon binding that can be detected. The ICycler
`machine used by Ehses couples thermal regulation with optical
`detection.” (Ex. 1008-Edwards at ¶82.)
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`In contrast, the DNA product shown in FIG. 3C is denatured at 95ºC prior to loading
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`on the gel, whereas product is detected under isothermal conditions in the Omitted
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`Step Reaction. In addition, the product is detected using staining in FIG. 3C, which
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`is an end-point detection method (i.e., not real time), whereas the Omitted Step
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`Reaction detects the product in real-time. Further confounding the interpretation of
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`FIG. 3C is the fact that only a small amount of starting material was used and the
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`reaction time was increased, either of which could, independently, cause an increase
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`in side-reactions. (See Ex. 1002-Ehses at 177-¶3.) Thus, the alleged connection
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`between the tendency to side-reactions shown in FIG. 3C and the detectability of
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`target product as claimed is so attenuated as to be irrelevant.
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`Thus, the Decision misapprehended the disclosures in Ehses. Moreover, as
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`explained in the next section, the actual reaction analyzed in the Petition and relied
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`on by Petitioner inherently results in detecting product prior to ten minutes, as
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`claimed. (See § II.B.)
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`Patent No. 9,562,263
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`Motion for Request for Reconsideration
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`Finally, Petitioner notes that the POPR and Decision both reference Ehses’s
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`purported disclosures regarding the “undesirability” of the omitting step. To the
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`extent the Decision rests on an “undesirability” finding (i.e., “teaching away”), the
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`Decision misapprehends the law. Undesirability is not relevant to anticipation. A
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`reference is no less anticipatory if, after disclosing the invention, the reference then
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`disparages it. MPEP § 2131.05; Celeritas Techs. Ltd. v. Rockwell Int’l Corp., 150
`
`F.3d 1354, 1361 (Fed. Cir. 1998); Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d
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`1319, 1323 (Fed. Cir. 2005); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1349
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`(Fed. Cir. 1999).
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`B.
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`The Board also misapprehended and overlooked the arguments set
`forth in the Petition and disclosures in Ehses showing that the
`reaction protocol relied on by Petitioner inherently detects product
`within 10 minutes
`Ehses inherently discloses “detecting the amplified target polynucleotide
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`sequence in real time within 10 minutes of subjecting the reaction mixture to
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`essentially isothermal conditions.” (Petition at 21-22.)
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`As an initial matter, Petitioner notes that there does not appear to be a dispute
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`that Ehses discloses real-time detection. (Decision at 12.) As set forth in the
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`Petition, this disclosure is express, not inherent. (Petition at 21-22 (citing Ex. 1002-
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`Ehses at 175-¶¶1, 3).) In particular, Ehses states:
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`Patent No. 9,562,263
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`Motion for Request for Reconsideration
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`“Upon addition of the enzymes, the amplification mixture was
`incubated 15–60 min[utes] in an ICycler (BioRAD) and the increase in
`fluorescence intensity was monitored.” (Id. (emphasis added).)
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`Thus, it cannot be reasonably disputed that real-time detection using fluorescence is
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`expressly disclosed in Ehses.
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`In fact, as the Petition shows, Ehses discloses the same type of real-time
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`detection that is described by the ’263 patent at examples 4, 5, and 6, which include
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`a description of monitoring an amplification in real-time using Sybr II, an
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`intercalating fluorescent dye. (Petition at 12 (citing Ex. 1001 at 27:1-47).) Ehses
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`discloses the same type of real-time detection using an ICycler and “an intercalating
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`fluorescence dye TOPRO-1.” (Ex. 1002-Ehses at 178-¶1 (emphasis added).) In
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`operation, this means that during the incubation process, fluorescence is monitored
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`and the increase in fluorescence correlates with increased product. (Petition at 21;
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`Ex. 1008-Edwards at ¶82.). This discloses real time detection of the amplified
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`product.
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`The only claim requirement that is not expressly disclosed in Ehses is that
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`product is detected by monitoring fluorescence intensity in real-time during the first
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`ten minutes of the reaction. This feature, however, is inherent because Ehses
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`monitors the reaction from its inception. (Ex. 1008-Edwards at ¶82.) The Board
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`misapprehended this aspect of Petitioner’s argument, and instead focused its analysis
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`8
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`Patent No. 9,562,263
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`on irrelevant disclosures in Ehses that relate to detection that occurs after the
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`Motion for Request for Reconsideration
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`reaction is stopped (i.e., not in real time):
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`“In both the SDA and nicking SDA reactions described in Ehses, the
`amplification mixture was ‘incubated 15–60 [minutes] . . . and the
`increase in fluorescence intensity was monitored. The reaction was
`stopped by addition of denaturing Stop/Loading dye and products
`were denatured at 95°C for 10 [minutes].’ Following the standard
`procedure outlined in Ehses, the detection of product took minimally a
`15 minute incubation in addition to a 10 minute denaturation step
`before the product is finally detected on the gel. The reaction can
`proceed as long as 60 minutes.” (Decision at 11-12 (emphasis added,
`internal citations omitted).)
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`The Board’s discussion of stopping the reaction by adding denaturing Stop/Loading
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`dye and subsequent denaturing for 10 minutes is not relevant to any issue in this case
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`because that portion of Ehses unequivocally relates to a type of detection that is not
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`performed in real-time—it occurs after the reaction is stopped. Petitioner never
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`argued that a post-reaction type of detection (e.g., staining) involving an additional
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`10-minute denaturation step and a gel corresponds to the claimed detecting step.
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`That type of detection is not real-time detection and cannot occur within ten minutes
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`because detection occurs only after the reaction is stopped. Ehses’s disclosure of
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`detection by staining has no bearing on whether Ehses’s separate disclosure of real-
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`time detection inherently discloses the claimed detecting step.
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`9
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`Patent No. 9,562,263
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`Motion for Request for Reconsideration
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`Instead of relying on irrelevant, post-reaction detection, the Petition relies on
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`Ehses’s disclosure of real-time detection. (Petition at 21.) Although the Board
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`recognized that real-time detection occurs in Ehses (Decision at 12), it
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`misapprehended when it occurs. The Board reaches this conclusion by
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`misapprehending the following disclosure in Ehses:
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`“An indication of the amplification of non-specific products is also
`given by a two step kinetic profile. When using an intercalating
`fluorescence dye TOPRO-1 in real-time detection, after about 20 min
`the fluorescence intensity signal shows a steep increase.” (Decision
`at 12 (citing Ex. 1002-Ehses at 178-¶1, emphasis added).)
`
`Importantly, the Board misinterpreted this disclosure to mean that real-time
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`detection of product occurs at the 20-minute mark:
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`“Ehses also discloses the use of real-time detection, but indicates that
`fluorescence intensity increases after 20 minutes. Thus, the Ehses
`reference itself indicates that using real-time detection based on
`fluorescence intensity will take longer than 10 minutes.” (Decision at
`12 (emphasis added, internal citations omitted).)
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`The Board has misapprehended Ehses. Ehses discloses that fluorescence, which is
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`a read-out of product detection, was detectable prior to the 20-minute mark, but was
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`present at a lower level during the first step in the two step kinetic profile. The 20-
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`minute mark represents the second step in the kinetic profile where a “steep increase”
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`in fluorescence occurred due to the accumulation of side products. An increase in
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`10
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`Patent No. 9,562,263
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`fluorescence is only possible when fluorescence is already present, albeit at a lower
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`Motion for Request for Reconsideration
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`level.
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`Ehses’s disclosure regarding real time detection parallels the disclosure of the
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`’263 patent at Example 4, which similarly describes the presence of side products,
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`but indicates that side products are easily distinguished from true product because
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`“The background products also generate fluorescence at a slower rate than the true
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`product.” (Ex. 1001 at 27:9-11.) In view of this disclosure, it is disingenuous for
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`the POPR to argue that the presence of side products would interfere with the
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`detection of the true product.
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`In practice, real time detection using fluorescence begins to show detectable
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`levels of product after just a few minutes, and certainly prior to ten minutes, as
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`discussed below. It appears that the Board has misapprehended what the results of
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`monitoring a reaction in real-time using an ICycler would look like—it is not the
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`case that only a “steep increase” would be detectable. This is confirmed by the Ehses
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`dissertation, which is also in the record (Ex. 1003, translation in Ex. 1004). This
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`dissertation includes a graph of real-time detection using fluorescence dye in Figure
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`3.4, which clearly shows product accumulating within a few minutes:
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`11
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`Patent No. 9,562,263
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`Motion for Request for Reconsideration
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`The graph shows that real-time detection using the intercalating dye TO-PRO-1 (as
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`disclosed in Ex. 1002-Ehses at 178-¶1) begins near time zero when fluorescence
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`begins to increase and continues during the reaction. The graph shows that there is
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`a steep increase around the 12-minute mark in the exponential growth plot, but also
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`shows that there were detectable levels of fluorescence far earlier in the process,
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`after just a couple of minutes. Thus, there is record evidence, overlooked by the
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`Board, tending to prove that the nSDA reaction described by Ehses would generate
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`detectable product within that time frame.
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`As explained in the Petition, the detecting step (and in particular detection
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`within ten minutes) is inherently disclosed in Ehses because “nSDA is performed
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`using the same components and under the same conditions as the claimed method,”
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`Patent No. 9,562,263
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`such that if detection using the claimed method in the ’263 patent results in detection
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`Motion for Request for Reconsideration
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`within ten minutes, the same must be true of the method disclosed in Ehses. (Petition
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`at 22; Ex. 1008-Edwards at ¶84); Atlas, 190 F.3d at 1348 (“An inherent structure,
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`composition, or function is not necessarily known. Once it is recognized that
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`interstitial and porous air were inherent … [it] amounts to no more than a claim to
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`the discovery of an inherent property of the prior art, not the addition of a novel
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`element.”).
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`Thus, as explained above with respect
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`to §§ II.A-B,
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`the Board
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`misapprehended Petitioner’s argument and the disclosures in Ehses, and should
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`reconsider its Decision by instituting inter partes review.
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`C.
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`The Board’s misapprehensions were due to incorrect statements
`made in the POPR
`The POPR includes several erroneous arguments that were adopted at least in
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`part by the Decision. First, the POPR argues that including an initial denaturation
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`step is desirable, and conversely that omitting such a step is undesirable. (POPR at
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`6.) This argument is irrelevant to an anticipation analysis (e.g., to Ground 1).
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`Desirability and teaching away are not applicable concepts with respect to
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`anticipation. MPEP § 2131.05; Celeritas, 150 F.3d at 1361; Pamlab, 412 F.3d at
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`1323; Atlas Powder, 190 F.3d at 1349. Nonetheless, as explained above, the Board
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`13
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`Patent No. 9,562,263
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`appeared to adopt aspects of this argument in rejecting Petitioner’s anticipation
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`Motion for Request for Reconsideration
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`ground based on Ehses. This misapprehends the law.
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`Next, the POPR includes an argument that incubation must occur for at least
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`15 minutes in Ehses, and consequently concluded that detectable product was not
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`produced prior to that time. (POPR at 9.) However, the total incubation time has
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`nothing to do with whether product is detectable using real time fluorescence
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`monitoring in an ICycler. Likewise, a 15-minute reaction time does not suggest the
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`absence of detectable product earlier than 15-minutes. That suggestion is
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`erroneous—for example, it may simply be preferred to wait for additional detectable
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`product to accumulate, even though product is detected earlier. Again, the Board
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`focused its analysis of the detecting step on this argument that Ehses discloses
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`running reactions for at least 15 minutes. (Decision at 12.) As shown above, this
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`misapprehends Ehses and focuses on an irrelevant aspect of its disclosure.
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`D. The Board did not follow Rule 42.108
`The Board rejected all of Petitioner’s grounds, including Ground 1 based on
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`anticipation by Ehses. (Decision at 6, 12.) Ground 1 was denied based on the
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`Board’s determination that Ehses does not inherently anticipate. Although the
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`Decision misapprehended and overlooked Petitioner’s actual argument, as explained
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`in the preceding section, the Decision also expresses agreement with Patent Owner’s
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`factual assertion that Ehses does not inherently disclose the detecting limitation. The
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`14
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`Patent No. 9,562,263
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`inherent teaching of a reference is a question of fact. In re Grasselli, 713 F.2d 731,
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`Motion for Request for Reconsideration
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`
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`739 (Fed. Cir. 1983). The POPR presents attorney argument without any
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`corresponding expert declaration to support that attorney argument. The POPR also
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`raises arguments that are demonstrably incorrect based on Ehses, including that real-
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`time detection can only occur after a reaction is concluded. (See, e.g., POPR at 10.)
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`At worst, this is a disputed issue of material fact; namely, whether Ehses inherently
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`discloses real-time detection using fluorescence that begins when the reaction starts
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`in an ICycler and stops when the incubation stops. (Ex. 1008-Edwards at ¶82
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`(explaining Ehses’s use of real-time detection and incubation).) Under 37 C.F.R. §
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`42.108, disputed issues of material must be resolved in Petitioner’s favor. Here, that
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`did not occur, and that misapprehends and overlooks the Board’s own rules.
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`III. CONCLUSION
`For the foregoing reasons, Petitioner respectfully requests rehearing under
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`Rule 42.71, and requests an inter partes review trial with the respect to the
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`Challenged Claims of the ’263 patent.
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`15
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`Patent No. 9,562,263
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`Date: August 29, 2018
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`Motion for Request for Reconsideration
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`Respectfully submitted,
`
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`GREENBERG TRAURIG, LLP
`
`
`By: /s/ Jonathan D. Ball
`Jonathan D. Ball, Ph.D.
`Registration No. 59,928
`GREENBERG TRAURIG, LLP
`MetLife Building
`200 Park Avenue, 38th Floor
`New York, New York, 10166
`ballj@gtlaw.com
`Phone: (212) 801-2223
`Fax: (212) 801-6400
`
`Melissa Hunter-Ensor, Ph.D.
`Registration No. 55,289
`GREENBERG TRAURIG, LLP
`One International Place, Suite 2000
`Boston, MA 02110
`hunterensorm@gtlaw.com
`Phone: (617) 310-6224
`Fax: (617) 310-6001
`
`Counsel for Petitioner
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`Patent No. 9,562,263
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`Motion for Request for Reconsideration
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`CERTIFICATE OF SERVICE
`The undersigned hereby certifies that a copy of the foregoing and any
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`supporting exhibits were served on counsel of record on August 29, 2018 by email
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`to:
`
`
`
`Aaron F. Barkoff, Ph.D. (Reg. No. 52,591)
`Christopher P. Singer, Ph.D. (Reg. No. 48,701)
`MCANDREWS, HELD & MALLOY, LTD.
`500 W. Madison St., 34th Floor
`Chicago, IL 60661
`Tel: (312) 775-8000
`Fax: (312) 775-8100
`Email: abarkoff@mcandrews-ip.com
`Email: csinger@mcandrews-ip.com
`Email: IonianIPR@mcandrews-ip.com
`
`
`
`Date: August 29, 2018
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`
`
`
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`
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`Respectfully submitted,
`
`GREENBERG TRAURIG, LLP
`
`
`By: /Jonathan Ball, Ph.D./
`Jonathan D. Ball, Ph.D.
`Registration No. 59,928
`GREENBERG TRAURIG, LLP
`MetLife Building
`200 Park Avenue, 38th Floor
`New York, New York, 10166
`ballj@gtlaw.com
`Phone: (212) 801-2223
`Fax: (212) 801-6400
`
`Counsel for Petitioner
`
`17
`
`

`

`Patent No. 9,562,263
`
`
`
`
`
`Motion for Request for Reconsideration
`
`CERTIFICATE OF COMPLIANCE
`This Petitioner’s Motion for Request for Reconsideration complies with the
`
`type-volume limitation of 37 C.F.R. § 42.24(a)(1)(v), which permits 15 pages for
`
`Petitioner’s Motion.
`
`
`
`
`
`
`Date: August 29, 2018
`
`
`
`
`
`
`
`Respectfully submitted,
`GREENBERG TRAURIG, LLP
`
`
`By: /Jonathan Ball, Ph.D./
`Jonathan D. Ball, Ph.D.
`Registration No. 59,928
`GREENBERG TRAURIG, LLP
`MetLife Building
`200 Park Avenue, 38th Floor
`New York, New York, 10166
`ballj@gtlaw.com
`Phone: (212) 801-2223
`Fax: (212) 801-6400
`
`Counsel for Petitioner
`
`18
`
`

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