`
`Filed on behalf of Ionian Technologies, LLC
`By: Aaron F. Barkoff, Ph.D.
`
`Christopher P. Singer, Ph.D.
`McAndrews, Held & Malloy, Ltd.
`500 West Madison Street
`Chicago, Illinois 60661
`
`
`
`
`
`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
`____________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`
`
`

`

`Patent Owner’s Preliminary Response
`IPR2018-00405
`
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION ..................................................................................................... 1 
`ARGUMENT ............................................................................................................. 2 
`A.  Ground 1: Ehses does not anticipate the claims .................................... 2 
`1. 
`Ehses fails to disclose at least four claim limitations ................. 3 
`a. 
`Ehses does not disclose “obtaining from an animal,
`plant or food, a sample comprising a target nucleic
`acid” .................................................................................. 4 
`Ehses does not disclose a method of amplification
`“without first subjecting the target nucleic acid to a
`thermal denaturation step associated with
`amplification of the target polynucleotide sequence” ...... 6 
`Ehses does not disclose “combining, in a single step,
`the obtained sample directly with an amplification
`reagent mixture or diluting the obtained sample and
`combining, in a single step, the diluted sample with an
`amplification reagent mixture” ......................................... 7 
`Ehses does not disclose “detecting the amplified target
`. . . within 10 minutes of subjecting the reaction
`mixture to isothermal conditions” .................................... 9 
`Ground 2: Ehses-Dissertation does not anticipate the claims ............. 11 
`1. 
`The petition fails to show that Ehses-Dissertation qualifies
`as a “printed publication” .......................................................... 12 
`Ehses-Dissertation fails to disclose at least three of the
`same claim limitations that are missing from Ehses ................. 16 
`a. 
`Ehses-Dissertation does not disclose “obtaining from
`an animal, plant or food, a sample comprising a target
`nucleic acid” ................................................................... 16 
`Ehses-Dissertation does not disclose a method of
`amplification “without first subjecting the target
`nucleic acid to a thermal denaturation step associated
`with amplification of the target polynucleotide
`sequence” ........................................................................ 18 
`
`B. 
`
`2. 
`
`b. 
`
`c. 
`
`d. 
`
`b. 
`
`i
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`

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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
`
`
`
`c. 
`
`b. 
`
`c. 
`
`2. 
`
`2. 
`
`2. 
`
`Ehses-Dissertation does not disclose “combining, in a
`single step, the obtained sample directly with an
`amplification reagent mixture or diluting the obtained
`sample and combining, in a single step, the diluted
`sample with an amplification reagent mixture”.............. 20 
`Ground 3: The claims are not obvious over Ehses and Ehses-
`Dissertation .......................................................................................... 21 
`1. 
`The combination of Ehses and Ehses-Dissertation fails to
`disclose all of the claim limitations .......................................... 21 
`In addition, the petition fails to adequately explain a
`motivation to combine or reasonable expectation of
`success ....................................................................................... 22 
`D.  Ground 4: Piepenburg does not anticipate the claims ......................... 24 
`1. 
`Piepenburg fails to disclose the limitations “arranged as in
`the claim” .................................................................................. 24 
`Piepenburg fails to disclose at least four claim limitations ...... 26 
`a. 
`Piepenburg does not disclose an amplification
`reaction mixture comprising either the first or second
`oligonucleotide recited in claim limitations 1(b)(iii)
`and 1(b)(iv) ..................................................................... 26 
`Piepenburg does not disclose “detecting the amplified
`target polynucleotide sequence in real time”.................. 29 
`Piepenburg does not disclose “detecting the amplified
`target . . . within 10 minutes of subjecting the reaction
`mixture to isothermal conditions” .................................. 32 
`Ground 5: The claims are not obvious over Piepenburg in view of
`Kong .................................................................................................... 34 
`1. 
`The combination of Piepenburg and Kong fails to disclose
`all of the claim limitations ........................................................ 34 
`In addition, the petition fails to adequately explain a
`motivation to combine or reasonable expectation of
`success ....................................................................................... 35 
`Ground 6: The claims are not obvious over Piepenburg in view of
`Kato ..................................................................................................... 38 
`
`C. 
`
`E. 
`
`F. 
`
`ii
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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
`
`1. 
`
`2. 
`
`The combination of Piepenburg and Kato fails to disclose
`all of the claim limitations ........................................................ 38 
`In addition, the petition fails to adequately explain a
`motivation to combine or reasonable expectation of
`success ....................................................................................... 39 
`G.  Ground 7: The claims are not obvious over Piepenburg in view of
`Ehses and Ehses-Dissertation .............................................................. 41 
`1. 
`The combination of asserted prior art fails to disclose all of
`the claim limitations .................................................................. 41 
`In addition, the petition fails to adequately explain a
`motivation to combine or reasonable expectation of
`success ....................................................................................... 42 
`H.  Ground 8: The claims are not obvious over Ehses and Ehses-
`Dissertation in view of Piepenburg ..................................................... 44 
`1. 
`The combination of asserted prior art fails to disclose all of
`the claim limitations .................................................................. 44 
`In addition, the petition fails to adequately explain a
`motivation to combine or reasonable expectation of
`success ....................................................................................... 44 
`CONCLUSION ........................................................................................................ 46 
`
`2. 
`
`2. 
`
`iii
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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
`
`TABLE OF AUTHORITIES
`
`CASES 
`Apple, Inc. v. DSS Tech. Mgmt., Inc.,
`IPR2015-00369 (PTAB Aug. 12, 2015) ............................................................... 13
`Argentum Pharms., LLC v. Research Corp. Techs., Inc.,
`IPR2016-00204 (PTAB May 23, 2016) ................................................................ 15
`Continental Can Co. v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991) .............................................................................. 5
`Helifix v. Blok-Lok, Ltd.,
`208 F.3d 1339 (Fed. Cir. 2000) ..........................................................................3, 7
`Howmedica Osteonics Corp. v. Zimmer, Inc.,
`640 F. App’x 951 (Fed. Cir. 2016) ....................................................................... 22
`Impax Labs., Inc. v. Aventis Pharms. Inc.,
`468 F.3d 1366 (Fed. Cir. 2006) ..........................................................................3, 7
`In re Hall,
`781 F.2d 897 (Fed. Cir. 1986) ....................................................................... 12, 13
`In re Klopfenstein,
`380 F.3d 1345 (Fed. Cir. 2004) ............................................................................ 12
`In re Lister,
`583 F.3d 1307 (Fed. Cir. 2009) ............................................................................ 12
`In re Oelrich,
`666 F.2d 578 (CCPA 1981) .................................................................................. 11
`In re Paulsen,
`30 F.3d 1475 (Fed. Cir. 1994) ................................................................................ 3
`In re Robertson,
`169 F.3d 743 (Fed. Cir. 1999) ..................................................................... 3, 5, 18
`In re Wyer,
`655 F.2d 221 (CCPA 1981) .................................................................................. 13
`Insite Vision Inc. v. Sandoz, Inc.,
`783 F.3d 853 (Fed. Cir. 2015) ................................................................. 22, 43, 45
`Kyocera Wireless Corp. v. Int’l Trade Comm’n,
`545 F.3d 1340 (Fed. Cir. 2008) ............................................................................ 12
`
`iv
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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
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`Liberty Mutual Ins. Co. v. Progressive Casualty Inc. Co.,
`CBM2012-00003 (PTAB Oct. 25, 2012) ............................................................. 12
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) ............................................................... 21, 35, 39
`Net MoneyIN, Inc. v. Verisign, Inc.,
`545 F.3d 1359 (Fed. Cir. 2008) ............................................................................ 25
`Novartis Pharm. Corp. v. Watson Labs., Inc.,
`611 F. App’x 988 (Fed. Cir. 2015) .......................................................... 23, 43, 45
`Par Pharm., Inc. v. TWi Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ............................................................... 21, 35, 39
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ............................................................... 22, 43, 45
`Philips Elec. & Pharm. Indus. Corp. v. Thermal & Elecs. Indus., Inc.,
`450 F.2d 1164 (3d Cir. 1971) ............................................................................... 13
`Procter & Gamble Co. v. Teva Pharms. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009) .............................................................................. 23
`Rexnord Indus., LLC v. Kappos,
`705 F.3d 1347 (Fed. Cir. 2013) .............................................................................. 3
`Sanofi-Synthelabo v. Apotex, Inc.,
`550 F.3d 1075 (Fed. Cir. 2008) ............................................................................ 24
`Seabery North America, Inc. v. Lincoln Global, Inc.,
`IPR2016-00904 (PTAB Nov. 3, 2016) ................................................................. 14
`SRI Int’l, Inc. v. Internet Sec. Sys. Inc.,
`511 F.3d 1186 (Fed. Cir. 2008) ............................................................................ 12
`Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc.,
`200 F.3d 795 (Fed. Cir. 1999) ................................................................................ 2
`
`STATUTES 
`35 U.S.C. § 102 ..................................................................................... 12, 16, 22, 42
`
`RULES 
`37 C.F.R. § 42.65 ................................................................................................ 5, 17
`
`
`v
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`

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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
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`INTRODUCTION
`
`U.S. Patent No. 9,562,263 (“the ‘263 patent”) concerns novel methods of
`
`isothermal DNA amplification. Claim 1 is representative:
`
`1. A method of amplifying a target polynucleotide sequence, the
`method comprising:
`(a) obtaining, from an animal, plant or food, a sample comprising a
`target nucleic acid . . .
`(b) without first subjecting the target nucleic acid to a thermal
`denaturation step associated with amplification of the target
`polynucleotide sequence, combining, in a single step, the obtained
`sample directly with an amplification reagent mixture or diluting
`the obtained sample and combining, in a single step, the diluted
`sample with an amplification reagent mixture, in either case, the
`amplification reagent mixture being free of bumper primers and
`comprising:
`(i) a polymerase,
`(ii) a nicking enzyme,
`(iii) a first oligonucleotide comprising a 5’ portion that comprises
`a nicking enzyme binding site that is non-complementary to
`the target polynucleotide sequence and a 3’ portion that
`hybridizes to the target polynucleotide sequence, and
`(iv) a second oligonucleotide comprising a 5’ portion that
`comprises a nicking enzyme binding site that is non-
`complementary to the target polynucleotide sequence and a 3’
`portion that hybridizes to the target polynucleotide sequence,
`(c) subjecting the reaction mixture . . . to essentially isothermal
`conditions to amplify the target polynucleotide sequence without
`the assistance of bumper primers, and
`(d) detecting the amplified target polynucleotide sequence in real
`time within 10 minutes of subjecting the reaction mixture to
`essentially isothermal conditions.
`
`Ex. 1001, 32:14-47 (emphasis added).
`
`1
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`

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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`Petitioner proposes constructions of numerous claim terms. Pet., 7-13. But
`
`no claim terms require construction at this stage. See Vivid Techs., Inc. v. Am. Sci.
`
`& Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (holding that “only those terms
`
`need be construed that are in controversy, and only to the extent necessary to
`
`resolve the controversy.”) Patent Owner reserves the right to propose claim
`
`constructions if the Board institutes inter partes review.
`
`Petitioner challenges claims 1-8 and 10-35 of the ‘263 patent on eight
`
`separate grounds, including anticipation and obviousness. As explained in this
`
`preliminary response, however, the asserted prior art fails to disclose many of the
`
`claim limitations (indicated in bold italics above). Further, in the obviousness
`
`grounds, the petition fails to specifically describe why a person of ordinary skill in
`
`the art would have been motivated to combine the references or, in doing so, would
`
`have had a reasonable expectation of success. For at least these reasons, the
`
`petition fails to establish a reasonable likelihood that Petitioners would prevail with
`
`respect to at least one of the challenged claims. The Board should therefore deny
`
`the petition and decline to institute inter partes review of the ‘263 patent.
`
`ARGUMENT
`A. Ground 1: Ehses does not anticipate the claims
`Petitioner asserts that Ehses anticipates claims 1-6, 8, 10-13, 15-16, and 18-
`
`35. Pet., 14-30. Ehses is a research article entitled “Optimization and design of
`
`2
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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
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`oligonucleotide setup for strand displacement amplification,” published in the
`
`Journal of Biochemical and Biophysical Methods in 2005. Ex. 1002.
`
`Anticipation is established when a single prior art references describes,
`
`either expressly or inherently, each and every element of the claim. In re
`
`Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999) (citation omitted). “[A]nticipation
`
`by inherent disclosure is appropriate only when the reference discloses prior art
`
`that must necessarily include the unstated limitation.” Rexnord Indus., LLC v.
`
`Kappos, 705 F.3d 1347, 1355 (Fed. Cir. 2013) (citation omitted).
`
`In addition, to be anticipating, a prior art reference must be enabling and
`
`must describe the claimed invention sufficiently to have placed it in possession of a
`
`person of ordinary skill in the field of the invention. Helifix v. Blok-Lok, Ltd., 208
`
`F.3d 1339, 1346 (Fed. Cir. 2000); In re Paulsen, 30 F.3d 1475, 1479 (Fed. Cir.
`
`1994). “Prior art is not enabling so as to be anticipating if it does not enable a
`
`person of ordinary skill in the art to carry out the invention.” Impax Labs., Inc. v.
`
`Aventis Pharms. Inc., 468 F.3d 1366, 1381 (Fed. Cir. 2006).
`
`Ehses fails to disclose at least four claim limitations
`
`1.
`Petitioner alleges that Ehses discloses, expressly or inherently, every
`
`limitation of claim 1. Pet., 15. Examination of Ehses, however, reveals that it fails
`
`to disclose at least four limitations that are in all of the claims of the ‘263 patent.
`
`3
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`Patent Owner’s Preliminary Response
`IPR2018-00405
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`The failure to disclose any one of these limitations defeats anticipation with respect
`
`to all of the claims challenged in ground 1.
`
`a.
`
`Ehses does not disclose “obtaining from an animal,
`plant or food, a sample comprising a target nucleic
`acid”
`
`The petition cites two statements in Ehses to support the allegation that
`
`Ehses discloses this limitation: (1) “This makes SDA valuable in diagnostics . . .”
`
`and (2) SDA is “an effective diagnostic tool, especially for detection of
`
`mycobacteria.” Pet., 15, 17 (quoting Ex. 1002, pp. 171, 183). Neither of these
`
`statements—nor any other part of Ehses—expressly mentions an animal, plant, or
`
`food sample. In fact, Ehses uses synthetic DNA as the target nucleic acid in its
`
`amplification reactions. See Ex. 1002, p. 176 (“The assembly differs from other
`
`SDA reaction setups by the use of short synthetic DNA oligonucleotides as starting
`
`template for the amplification reaction . . . .”). Thus, Petitioner must show that
`
`Ehses inherently discloses this limitation.
`
`Petitioner’s only evidence supporting a position that Ehses inherently
`
`discloses “obtaining from an animal, plant or food, a sample comprising a target
`
`nucleic acid” is unsupported and conclusory testimony from its expert, Dr.
`
`Edwards. Specifically, Petitioner cites paragraph 65 of the Edwards Declaration,
`
`which states: “A POSA would recognize that, for detection of mycobacteria,
`
`samples can be obtained from an animal, plant, or food.” Ex. 1008, ¶ 65.
`
`4
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`Petitioner also cites paragraph 69 of the Edwards Declaration, which states, “[a]
`
`POSA would understand that diagnostic applications encompass the analysis of
`
`samples derived from animals, plants, or food, all of which contain
`
`polynucleotides” and “[a] POSA would also understand that mycobacteria refers to
`
`a family of related bacteria that can infect humans and animals, but are also present
`
`in the environment, including soil, air, water and food sources.” Id., ¶ 69.
`
`Unsupported and conclusory testimony such as Dr. Edwards’s is entitled to
`
`little or no weight. See 37 C.F.R. § 42.65 (“[e]xpert testimony that does not
`
`disclose the underlying facts or data on which the opinion is based is entitled to
`
`little or no weight”). Moreover, Dr. Edwards’s testimony is undercut by his own
`
`statement that mycobacteria “are also present in the environment, including soil,
`
`air, [and] water.” Ex. 1008, ¶ 69. Because mycobacteria are present in soil, air,
`
`and water, Ehses’s teaching that SDA “is an effective diagnostic tool, especially
`
`for detection of mycobacteria” does not necessarily disclose diagnostic testing of
`
`an “animal, plant or food” sample, as recited in the claims of the ‘263 patent. See
`
`Robertson, 169 F.3d at 745 (“To establish inherency, the extrinsic evidence ‘must
`
`make clear that the missing descriptive matter is necessarily present in the thing
`
`described in the reference.’”) (quoting Continental Can Co. v. Monsanto Co., 948
`
`F.2d 1264, 1268 (Fed. Cir. 1991)).
`
`5
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`IPR2018-00405
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`b.
`
`Ehses does not disclose a method of amplification
`“without first subjecting the target nucleic acid to a
`thermal denaturation step associated with
`amplification of the target polynucleotide sequence”
`
`In support of its allegation that Ehses discloses this limitation, Petitioner
`
`points to a single sentence in Ehses: “When starting with less template, omitting
`
`the initial denaturation step or increasing the reaction time, the standard SDA
`
`system as well as the nicking system shows the tendency to side-reactions.” Pet.,
`
`17 (quoting Ex. 1002, p. 177) (Petitioner’s emphasis). Based on this single
`
`sentence, Petitioner concludes, “[a]ccordingly, Ehses demonstrates that thermal
`
`denaturation is not required for amplification of a Target.” Pet., 17 (Petitioner’s
`
`emphasis). The Edwards Declaration, which Petitioner cites in support of its
`
`conclusion, simply parrots the petition. See Ex. 1008, ¶ 71.
`
`The sentence of Ehses upon which Petitioner relies for disclosure of omitting
`
`an initial denaturation step expressly teaches the reader not to omit an initial
`
`denaturation step—because doing so “shows the tendency to side-reactions.” Ex.
`
`1002, p. 177. Indeed, a few sentences later, when describing the types of side-
`
`reactions that can occur, Ehses teaches that “the initial denaturation step before
`
`addition of enzymes can delay the formation of the [primer] dimer.” Id. Thus,
`
`Ehses teaches that including an initial denaturation step is desirable. In fact, the
`
`primary objective of Ehses was “to tackle the difficulties regarding the specificity
`
`of the [isothermal amplification] reaction.” Id., Abstract. Accordingly,
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`6
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`Patent Owner’s Preliminary Response
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`Petitioner’s argument regarding the initial thermal denaturation step is exactly
`
`backwards.
`
`Moreover, consistent with Ehses’s teaching not to omit an initial
`
`denaturation step, the only DNA amplification protocols described in Ehses
`
`include such a step. Specifically, when describing the protocol for standard SDA,
`
`Ehses states, “[a]fter addition of template DNA into final volume of 24 µl and
`
`before addition of any enzymes, the reaction sample was incubated for 3 min at 95
`
`°C, followed by 1 min at 55 °C.” Ex. 1002, p. 175 (emphasis added). Likewise,
`
`when describing the protocol for nicking SDA, Ehses states, “[a]fter addition of
`
`template DNA into final volume of 24 µl and before addition of any enzymes, the
`
`reaction sample was incubated for 3 min at 95 °C, followed by 1 min at 55 °C.”
`
`Id. (emphasis added). There is no teaching anywhere in Ehses of how to perform
`
`SDA without an initial denaturation step. Thus, even if one were to accept
`
`Petitioner’s argument that Ehses’s teaching not to omit the initial denaturation step
`
`somehow discloses omitting such a step, Ehses does not enable a person of
`
`ordinary skill in the art to perform isothermal DNA amplification without an initial
`
`denaturation step. See Helifix, 208 F.3d at 1346 (prior art must be enabling);
`
`Impax, 468 F.3d at 1381 (same).
`
`c.
`
`Ehses does not disclose “combining, in a single step,
`the obtained sample directly with an amplification
`reagent mixture or diluting the obtained sample and
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`7
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`combining, in a single step, the diluted sample with an
`amplification reagent mixture”
`
`The premise of Petitioner’s argument that Ehses discloses this claim
`
`limitation appears to be that the amplification method of Ehses does not require a
`
`thermal denaturation step. Specifically, the petition states: “Ehses discloses a
`
`single step method. Because thermal denaturation is not required, the sample and
`
`AmpRxn components are combined and incubated in a single step.” Pet., 18. In
`
`support, the petition cites paragraph 72 of the Edwards Declaration, which simply
`
`states: “Ehses discloses a single step method. Because a thermal denaturation step
`
`is not required by Ehses, the sample may be combined with the reaction
`
`components in a single step.” Ex. 1008, ¶ 72. As explained above, however,
`
`Ehses teaches that an initial denaturation step should be included, not omitted.
`
`Thus, the premise of Petitioner’s argument is false.
`
`Furthermore, even if the premise were not wrong, Ehses still does not
`
`disclose a single-step amplification reaction. That is because Ehses’s protocols
`
`include an incubation step of 1 minute at 55 °C after the addition of template DNA
`
`and before the addition of DNA polymerase (which catalyzes DNA synthesis). For
`
`example, Ehses’s protocol for standard SDA states:
`
`After addition of template DNA into final volume of 24 µl and before
`addition of any enzymes, the reaction sample was incubated for 3 min
`at 95 °C, followed by 1 min at 55 °C. Upon addition of the enzymes,
`
`8
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`the amplification mixture was incubated 15-60 min in an ICycler
`(BioRAD) and the increase in fluorescence intensity was measured.
`
`Ex. 1002, p. 175 (emphasis added). Ehses’s protocol for nicking SDA includes the
`
`same instructions. Id. Thus, even if one were to accept that Ehses teaches
`
`amplification reactions that omit an initial denaturation step, Ehses still would not
`
`disclose an amplification reaction wherein the sample is combined, in a single step,
`
`directly with an amplification reagent mixture comprising a polymerase, a nicking
`
`enzyme, and oligonucleotides, as claimed.
`
`d.
`
`Ehses does not disclose “detecting the amplified target
`. . . within 10 minutes of subjecting the reaction
`mixture to isothermal conditions”
`
`Ehses does not disclose any results of amplification reactions in which target
`
`DNA was detected within ten minutes—nor does Ehses state that its amplification
`
`reactions are capable of producing detectable target within ten minutes. In fact,
`
`both of the SDA protocols that Ehses discloses require incubation with DNA
`
`polymerase for a minimum of 15 minutes. See Ex. 1002, p. 175 (stating, for both
`
`standard SDA and nicking SDA, that “the amplification mixture was incubated 15-
`
`60 min”).
`
`The petition appears to acknowledge this fact, stating, “Ehses discloses that
`
`the SDA and nSDA amplification mixtures were incubated 15-60 minutes and the
`
`increase in fluorescence intensity was monitored.” Pet., 22 (citing Ex. 1002, p.
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`9
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`175). Nevertheless, Petitioner argues that Ehses inherently discloses detecting the
`
`amplified target within 10 minutes because, according to the petition, (1) “the
`
`reaction is monitored throughout the incubation [and] the presence of amplification
`
`product is detected as it accumulates” and (2) “nSDA is performed using the same
`
`components and under the same conditions as the claimed method, [and therefore]
`
`a POSA understands that the time to detection would necessarily be the same.”
`
`Pet., 22. But neither of these arguments withstands scrutiny.
`
`Contrary to Petitioner’s first argument, Ehses does not state that the
`
`amplification reactions were monitored “throughout the incubation.” Nor does
`
`Ehses disclose the time point at which monitoring began. Instead, Ehses states
`
`only that “the amplification mixture was incubated 15-60 min in an ICycler
`
`(BioRAD) and the increase in fluorescence intensity was monitored.” Ex. 1002, p.
`
`175. Indeed, the fact that Ehses’s amplification reactions were always incubated
`
`for at least 15 minutes suggests that the reactions did not produce detectable target
`
`DNA before that time. If that is true, then it would be impossible using Ehses’s
`
`methods to detect amplified target within 10 minutes of subjecting the reaction to
`
`isothermal conditions, as the claims of the ‘263 patent require. And even if the
`
`Ehses reactions would sometimes yield detectable product within 10 minutes,
`
`inherency “may not be established by probabilities or possibilities. The mere fact
`
`10
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`that a certain thing may result from a given set of circumstances is not sufficient.”
`
`In re Oelrich, 666 F.2d 578, 581 (CCPA 1981).
`
`With regard to Petitioner’s second argument—that the reaction conditions in
`
`Ehses are the same as those in the ‘263 patent claims, and therefore “the time to
`
`detection would necessarily be the same”—the petition fails to show that the
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`premise is true. That is, the petition provides no comparison of the reaction
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`conditions disclosed in Ehses to the reaction conditions recited in the claims. And
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`the only evidence that the petition cites in support of the argument is, once again,
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`conclusory and unsupported testimony of Dr. Edwards. See Pet., 22 (citing Ex.
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`1008, ¶ 84). The cited paragraph of the Edwards Declaration again merely parrots
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`the petition. Thus, Petitioner’s second argument regarding this claim limitation
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`fails.
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`Accordingly, the petition fails to establish a reasonable likelihood of
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`prevailing on ground 1 with respect to any of the challenged claims.
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`B. Ground 2: Ehses-Dissertation does not anticipate the claims
`Petitioner asserts that Ehses-Dissertation anticipates the same claims as
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`those challenged in ground 1: claims 1-6, 8, 10-13, 15-16, and 18-35.1 Pet., 31-42.
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`                                                            
`1 The petition does not articulate a “meaningful distinction” between Ehses and
`Ehses-Dissertation “in terms of their relative strengths and weaknesses with
`respect to application of the prior art disclosures to one or more claim limitations.”
`Liberty Mutual Ins. Co. v. Progressive Casualty Inc. Co., CBM2012-00003, Paper
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`11
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`

`

`Patent Owner’s Preliminary Response
`IPR2018-00405
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`
`
`
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`Ehses-Dissertation appears to be a Ph.D. dissertation authored by Sylvia Ehses,
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`who is also the first author of the Ehses article. Ex. 1003. Ehses-Dissertation is
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`written in German. Petitioner filed an English translation of Ehses-Dissertation as
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`Exhibit 1004.
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`1.
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`The petition fails to show that Ehses-Dissertation qualifies
`as a “printed publication”
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`A “determination of whether a reference is a ‘printed publication’ under 35
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`U.S.C. § 102(b) involves a case-by-case inquiry into the facts and circumstances
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`surrounding the reference’s disclosure to members of the public.” In re
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`Klopfenstein, 380 F.3d 1345, 1350 (Fed. Cir. 2004). The Federal Circuit has held
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`that “public accessibility” is the touchstone in determining whether a reference is a
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`“printed publication” under § 102. In re Hall, 781 F.2d 897, 898-99 (Fed. Cir.
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`1986). “A reference is publicly accessible ‘upon a satisfactory showing that such
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`document has been disseminated or otherwise made available to the extent that
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`persons interested and ordinarily skilled in the subject matter or art exercising
`
`reasonable diligence, can locate it . . . .’” Kyocera Wireless Corp. v. Int’l Trade
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`Comm’n, 545 F.3d 1340, 1350 (Fed. Cir. 2008) (quoting SRI Int’l, Inc. v. Internet
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`Sec. Sys. Inc., 511 F.3d 1186, 1194 (Fed. Cir. 2008)); In re Lister, 583 F.3d 1307,
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`1315 (Fed. Cir. 2009).
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`                                                                                                                                                                                                
`7 at 2 (PTAB Oct. 25, 2012). This is a further reason to deny institution of ground
`2, in addition to those reasons explained in this section.
`
`12
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`

`

`Patent Owner’s Preliminary Response
`IPR2018-00405
`
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`
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`A party seeking to introduce a reference “should produce sufficient proof of
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`its dissemination or that it has otherwise been available and accessible to persons
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`concerned with the art to which the document relates and thus most likely to avail
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`themselves of its contents.” In re Wyer, 655 F.2d 221, 227 (CCPA 1981) (quoting
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`Philips Elec. & Pharm. Indus. Corp. v. Thermal & Elecs. Indus., Inc., 450 F.2d
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`1164, 1171 (3d Cir. 1971)). In Hall, for example, the court found that a
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`dissertation qualified as a “printed publication” where the party produced an
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`affidavit from a librarian regarding the “procedure as to indexing, cataloging, and
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`shelving of theses” at the library that held a copy of the dissertation. 781 F.2d at
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`899. See also Apple, Inc. v. DSS Tech. Mgmt., Inc., IPR2015-00369, Paper 14 at 5
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`(PTAB Aug. 12, 2015) (requiring a “threshold showing” of public availability in
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`order to institute trial).
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`In this case, Petitioner has introduced no such evidence. Petitioner alleges
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`that Ehses-Dissertation “was published on August 7, 2005.” Pet., 30. But
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`Petitioner cites no evidence in support of that allegation. The Edwards Declaration
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`repeats the allegation, again citing no evidence. Ex. 1008, ¶ 116. It appears
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`possible that Petitioner’s allegation is based on the following statement in Ehses-
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`Dissertation: “Date of the oral examination: 07.08.2005.” Ex. 1004, p. 3. But even
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`if that statement is Petitioner