`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_______________
`
`PFIZER, INC.,
`Petitioner,
`
`v.
`
`CHUGAI PHARMACEUTICAL CO., LTD.,
`Patent Owner.
`
`_______________
`
`Case IPR2017-01357
`Patent No. 7,332,289 B2
`_______________
`
`
`
`PETITIONER’S REPLY TO PATENT OWNER’S RESPONSE
`
`
`
`

`

`IPR2017-01357
`Patent No. 7,332,289 B2
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION ........................................................................................... 1
`
`
`
`
`
`ARGUMENT ................................................................................................... 3
`
`A. Ground I: Shadle anticipates the challenged claims. ........................... 3
`
`
`
`
`
`
`
`Even if the preamble were limiting, and even under Patent
`Owner’s erroneous construction, Shadle would disclose it. ....... 3
`
`Shadle expressly or inherently discloses each step of the
`claimed process. .......................................................................... 6
`
`a. Step 1: “applying the antibody-containing sample to
`affinity chromatography on Protein A or Protein G” ................. 6
`b. Step 2: “eluting the antibody with an acidic aqueous
`solution of low conductivity having a molarity of 100mM or
`less” ............................................................................................. 6
`c. Step 3: “neutralizing the eluate from step (2) to form
`particles by addition of a buffer to raise the pH to 4 to 8 to form
`particles, wherein the molarity of the neutralized eluate is
`100mM or less” ........................................................................... 9
`i. Shadle’s neutralized eluate inherently has a molarity of
`100mM or less. .................................................................. 10
`ii. Shadle’s method inherently forms particles. .............. 15
`d. Step 4: “removing the particles thereby to remove
`contaminant DNA in the sample” ............................................. 19
`The dependent claims are not separately patentable. ................ 20
`
`a. Claim 2: The method according to claim 1, wherein the
`acidic aqueous solution of low conductivity has a molarity of
`50mM or less. ............................................................................ 20
`b. Claim 3 (and dependent claim 4): The method according to
`claim 1, wherein the acidic aqueous solution of low
`conductivity is selected from the group consisting of aqueous
`solutions of hydrochloric acid, citric acid, and acetic acid. ...... 21
`
`ii
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`

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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
`c. Claim 5: The method according to claim 1, wherein the
`contaminant DNA is present at a DNA concentration of 22.5
`pg/ml or less in the treated sample containing an antibody. ..... 22
`d. Claim 13: The method according to claim 1, wherein the
`particles are removed by filtration through a filter. .................. 23
`Ground II: At a minimum, the challenged claims would have been
`obvious. ............................................................................................... 23
`
`B.
`
`
`
`
`
`All claims are prima facie obvious over Shadle. ...................... 23
`
`There is no evidence of secondary considerations. .................. 24
`
` CONCLUSION .............................................................................................. 25
`
`
`
`
`
`
`
`
`iii
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`

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`IPR2017-01357
`Patent No. 7,332,289 B2
`
`
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Atlas Powder Co. v. Ireco, Inc.,
`190 F.3d 1342 (Fed. Cir. 1999) .......................................................................... 11
`
`Aylus Networks, Inc. v. Apple Inc.,
`856 F.3d 1353 (Fed. Cir. 2017) ............................................................................ 4
`
`Crown Operations Int’l, Ltd. v. Solutia Inc.,
`289 F.3d 1367 (Fed. Cir. 2002) .......................................................................... 18
`
`Geneva Pharms., Inc. v. GlaxoSmithKline PLC,
`349 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 16
`
`Genzyme Therapeutic Prod. Ltd. v. Biomarin Pharm. Inc.,
`825 F.3d 1360 (Fed. Cir. 2016) ............................................................................ 7
`
`Hewlett-Packard Co. v. Mustek Sys.,
`340 F.3d 1314 (Fed. Cir. 2003) .......................................................................... 24
`
`Idemitsu Kosan Co. v. SFC Co.,
`870 F.3d 1376 (Fed. Cir. 2017) ............................................................................ 5
`
`In re Kahn,
`441 F.3d 977 (Fed. Cir. 2006) ...................................................................... 13, 24
`
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................................... 18
`
`In re King,
`801 F.2d 1324 (Fed. Cir. 1986) .......................................................................... 11
`
`King Pharm., Inc. v. Eon Labs, Inc.,
`616 F.3d 1267 (Fed. Cir. 2010) ..................................................10, 11, 18, 19, 21
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 17
`
`iv
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`

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`IPR2017-01357
`Patent No. 7,332,289 B2
`
`Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp.,
`831 F.3d 1350 (Fed. Cir. 2016) .................................................................... 21, 22
`
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) .......................................................................... 11
`
`Schering Corp. v. Geneva Pharm., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 17
`
`SmithKline Beecham Corp. v. Apotex Corp.,
`403 F.3d 1331 (Fed. Cir. 2005) ...................................................................... 2, 11
`
`Valmont Indus., Inc. v. Lindsay Corp.,
`2018 WL 2130455 (Fed. Cir. May 9, 2018) ......................................................... 8
`
`Zoltek Corp. v. United States,
`815 F.3d 1302 (Fed. Cir. 2016) .......................................................................... 18
`
`Statutes
`
`37 C.F.R. §42.23 ........................................................................................................ 7
`
`37 C.F.R. §42.100(b) ................................................................................................. 1
`
`37 C.F.R. §42.121 .................................................................................................... 23
`
`
`
`v
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`

`

`
`
`INTRODUCTION
`
`This trial turns on whether the ’289 patent’s claimed method for removing
`
`contaminant DNA is patentably distinct from Shadle, a reference never considered
`
`by the Examiner before the ’289 patent issued and which the European Patent Office
`
`(“EPO”) later adopted as novelty-destroying prior art during prosecution of foreign
`
`counterparts. This Board instituted review on grounds of anticipation and
`
`obviousness after “decid[ing] that Shadle supports a reasonable likelihood that at
`
`least one of the challenged claims is unpatentable.” Dec. Inst. 35. Patent Owner’s
`
`Response does not support a different result.
`
`As an initial matter, Patent Owner admits that its the Response is premised on
`
`a host of narrow claim constructions. Resp. 12–23. Regardless of whether these
`
`constructions would apply in an infringement action, they are not the “broadest
`
`reasonable construction” that governs these proceedings. 37 C.F.R. §42.100(b).
`
`When the claims are properly construed under that standard, Patent Owner cannot
`
`avoid anticipation. Indeed, Patent Owner does not dispute the calculations of
`
`Petitioner’s expert, Dr. Przybycien, which show that all of the claimed steps are at
`
`least inherently disclosed by Shadle under their proper constructions.
`
`Unable to challenge those calculations, Patent Owner and its experts instead
`
`apply a legal standard that contradicts binding precedent. According to Patent
`
`Owner, inherency requires proof that any other result is “impossible.” Resp. 33. But
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`the Federal Circuit has rejected that standard: Petitioner does “not need to prove
`
`that it was impossible” to practice Shadle without reading on the claims, “but merely
`
`that … the natural result flowing from the operation as taught in the prior art would
`
`result in the claimed” invention. SmithKline Beecham Corp. v. Apotex Corp., 403
`
`F.3d 1331, 1343 (Fed. Cir. 2005) (quotation omitted). When properly applied, the
`
`legal standard is easily met here: As Dr. Przybycien’s unrebutted testimony shows,
`
`the natural result flowing from Shadle’s method is the same result claimed in the
`
`ʼ289 patent. EX1036 ¶17. Shadle thus anticipates the claims.
`
`At a minimum, the claims would have been obvious. While arguing that
`
`Shadle does not “always” result in the claimed invention, Patent Owner does not
`
`dispute that it “may.” Resp. 3. Thus, starting from Shadle, a POSA would have
`
`arrived at the claimed invention by applying no more than conventional methods and
`
`ordinary skill. EX1036 ¶¶68–70. No secondary considerations suggest otherwise.
`
`While Patent Owner touts the ʼ289 patent as “revolutionary” (Resp. 1), its experts
`
`could not cite a single commercial use of the claimed invention. Indeed, they
`
`admitted that column chromatography—the same process that the ʼ289 patent
`
`allegedly made obsolete—continues to dominate the industry.
`
`In sum, the Board should find the challenged claims anticipated and obvious.
`
`2
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`

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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
` ARGUMENT
`A. Ground I: Shadle anticipates the challenged claims.
`
`Even if the preamble were limiting, and even under Patent
`Owner’s erroneous construction, Shadle would disclose it.
`
`Starting with the independent claim 1, Patent Owner construes the preamble
`
`narrowly as “[a] method comprising the listed steps, wherein in the practice of the
`
`listed steps contaminant DNA is removed from a sample containing an antibody.”
`
`Resp. 13. Patent Owner’s position on the scope of the preamble is unclear, but even
`
`accepting Patent Owner’s proposed construction, Shadle discloses it.
`
`Throughout its argument that Shadle does not disclose the preamble, Patent
`
`Owner characterizes “the heart of the claimed invention as facilitating elimination
`
`of the[] additional, post-claim steps in Shadle that Petitioner says accomplish DNA
`
`removal—the same well-known additional
`
`‘complicated chromatographic
`
`processes’ of the prior art criticized by ’289.” Resp. 26. But Patent Owner never
`
`explains how this alleged characterization is relevant. To the extent Patent Owner
`
`contends the preamble necessitates exclusion of “additional, post-claim steps” (id.),
`
`that is not the preamble’s broadest reasonable interpretation.1
`
`
`1 Nevertheless, by advocating a narrow construction in this proceeding, Patent
`
`Owner is estopped from asserting a broader claim scope in any future litigation. See
`
`Aylus Networks, Inc. v. Apple Inc., 856 F.3d 1353, 1361 (Fed. Cir. 2017).
`
`3
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
`Patent Owner does not dispute that the claim “is a ‘comprising’ claim,” which
`
`means that “‘other elements may be added and still form a construct within the scope
`
`of the claim.’” Dec. Inst. 24 (quoting Genentech, Inc. v. Chiron Corp., 112 F.3d
`
`495, 501 (Fed. Cir. 1997)). The same is true for Patent Owner’s proposed
`
`construction of the preamble, which also uses the term “comprising.” Resp. 13.
`
`Thus, whether the preamble is construed as limiting or not, it does not exclude
`
`“additional chromatography steps beyond those expressly recited in [the] claims.”
`
`Dec. Inst. 24. Indeed, Patent Owner admits that “a practitioner performing the
`
`Challenged Claims might choose to employ further chromatography.” Resp. 13 n.8.
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`Patent Owner’s expert agrees. EX1034, 44:13–24 (Dr. Cramer) (“Q. So we look at
`
`claim one, would a POSA understand claim one to exclude the use of further
`
`purification by column chromatography after step [four]? A. No.”).
`
`To be clear, the recited steps 1–4 require and result in the removal of
`
`contaminant DNA. Id.; EX1036 ¶6. As the Petition explained (and as explained
`
`below), the same steps of Shadle’s process also necessarily result in removing
`
`contaminant DNA. Thus, even under Patent Owner’s construction, Shadle discloses
`
`the preamble’s purported requirement of removing contaminant DNA. EX1036
`
`¶¶18–21. While Shadle also discloses additional chromatography steps, Patent
`
`Owner’s construction does not exclude them.
`
`4
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
`Rather than dispute this, Patent Owner contends that the Petition did “not
`
`assert [that] Shadle inherently discloses the preambles.” Resp. 26 n.13. Patent
`
`Owner is mistaken. To the extent the preamble requires that “step 4’s
`
`removing/filtering … actually removes contaminant DNA,” (id. at 13), Petitioner
`
`showed that Shadle “inherently discloses” just that. Pet. 39–40 (“[Shadle] either
`
`expressly or at least inherently discloses the final step 4 of the claimed purification
`
`process of removing particles to thereby remove contaminant DNA.” (emphasis
`
`added)).2 Shadle thus discloses the preamble under Patent Owner’s construction.
`
`
`2 Petitioner argued this in the context of step 4 (rather than the preamble), but this
`
`makes no difference. Patent Owner’s construction of the preamble could just as
`
`easily have been a construction of step 4, and Patent Owner could (and did) respond
`
`to Petitioner’s argument. In any event, the Board’s rules do not require Petitioner to
`
`anticipate Patent Owner’s construction of the preamble. See Idemitsu Kosan Co. v.
`
`SFC Co., 870 F.3d 1376, 1381 (Fed. Cir. 2017) (patent owners’ counterarguments
`
`need not be “preemptively addressed by the petition”).
`
`5
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
`
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`Shadle expressly or inherently discloses each step of the
`claimed process.
`a.
`
`Step 1: “applying the antibody-containing sample to
`affinity chromatography on Protein A or Protein G”
`
`As the Petition explains, Shadle expressly discloses this step (Pet. 28–29) and
`
`that is not disputed (see Resp. 24–27). EX1036 ¶23
`
`b.
`
`Step 2: “eluting the antibody with an acidic aqueous
`solution of low conductivity having a molarity of
`100mM or less”
`
`Patent Owner and its expert, Dr. Cramer, do not dispute that Shadle discloses
`
`‘eluting the antibody with an acidic aqueous solution of low conductivity.’ See
`
`Resp. 27–29; EX2015 ¶¶53–55; EX1034 70:22–71:1; EX1036 ¶23. Nor do they
`
`dispute Dr. Przybycien’s calculations that, starting with any of four conventional
`
`buffer preparations, Shadle meets the claimed molarity limitation. See Resp. 27–29;
`
`EX2015 ¶¶53–55; EX1034 102:1–23. Instead, unable to challenge the calculation’s
`
`accuracy, Patent Owner argues that the calculations are improper supplemental
`
`information.
`
`Dr. Przybycien’s unchallenged calculations (EX1026; EX1027)—which
`
`show that the “total molarity” of the solution in step 2 is below 100mM—are
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`6
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`Patent No. 7,332,289 B2
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`admissible.3 Patent Owner’s contrary argument presumes a petition must contain all
`
`evidence used at trial, and that additional evidence may be submitted only with
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`“permission from the Board.” Resp. 28 n.14. Not so.
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`The purpose of trial is to develop the factual record within the contours
`
`established by the institution decision. Thus, “the introduction of new evidence in
`
`the course of the trial is to be expected in inter partes review trial proceedings and,
`
`as long as the opposing party is given notice of the evidence and an opportunity to
`
`respond to it, the introduction of such evidence is perfectly permissible.” Genzyme
`
`Therapeutic Prod. Ltd. v. Biomarin Pharm. Inc., 825 F.3d 1360, 1366 (Fed. Cir.
`
`2016). That is what happened here.
`
`The Petition construed the term “molarity” to mean “a measure of the
`
`concentration of a given solute within a solution in terms of the moles of that solute
`
`contained per liter of solution.” Pet. 24. Dr. Przybycien’s opening declaration thus
`
`calculated molarity under that construction. In its Institution Decision, the Board
`
`construed “the term ‘molarity’” differently, as “the total concentration of solute
`
`
`3 Dr. Pryzbycien prepared EX1027 in response to Patent Owner’s arguments in its
`
`Response and during his deposition. EX1036 ¶¶8–10. As an exhibit prepared to
`
`support arguments in Petitioner’s Reply that “respond to arguments raised in the …
`
`patent owner response,” EX1027 is admissible. 37 C.F.R. §42.23.
`
`7
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`present in the solution, rather than the concentration of one particular solute.” Dec.
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`Inst. 10. Dr. Przybycien recalculated molarity under the Board’s construction, and
`
`confirmed that, regardless of the construction, Shadle inherently meets the molarity
`
`limitations and anticipates the claims. EX1026; EX1036 ¶¶10, 37–38.
`
`Patent Owner’s challenge to Dr. Przybycien’s updated calculations is “a back-
`
`door attempt to challenge whether the Board properly instituted review.” Valmont
`
`Indus., Inc. v. Lindsay Corp., 2018 WL 2130455 at *4 (Fed. Cir. May 9, 2018). If
`
`anything, the calculations were provided early, not late: “[A] petitioner may submit
`
`additional evidence in the reply in response to the patent owner response,” and thus
`
`Petitioner could have (and has) served Dr. Przybycien’s updated calculations with
`
`this Reply. Id. at *3. In an abundance of caution, Petitioner also provided them to
`
`Patent Owner three months before this Reply—before Dr. Przybycien’s first
`
`deposition and a full month before Patent Owner’s Response was due. Patent Owner
`
`will get a second opportunity to examine Dr. Przybycien following this Reply. In
`
`short, Patent Owner has had every opportunity to respond to Dr. Przybycien’s
`
`updated calculations, and suffered no prejudice by receiving them early. See id. at
`
`*4 (finding no prejudice where patent owner “cross-examined [the expert], filed
`
`observations with the Board, and addressed the evidence at oral argument before the
`
`Board”).
`
`8
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
`On the merits, Patent Owner has no response to Dr. Przybycien’s updated
`
`calculations. They track the Board’s claim construction and indisputably show that
`
`for each of the four conventional ways of making Shadle’s citrate buffer, total
`
`molarity remains below 100mM. EX1036 ¶¶37–38; EX1026 1–2; EX1027 1–2.
`
`Neither Patent Owner nor its experts contest this. EX1036 ¶37; EX1034 102:1–4
`
`(“Q. Okay. Again, you don’t dispute that the four ways for making citrate buffer are
`
`among those that a POSA would have considered, right? A. Correct.”), 149:8–12
`
`(“Q. You don’t dispute that under the four ways that Dr. Przybycien made, proposes
`
`making the citrate buffer that each of those total molarities would be under a hundred
`
`millimolars, right? A. Correct.”); EX1034, 149:1–17.
`
`c.
`
`Step 3: “neutralizing the eluate from step (2) to form
`particles by addition of a buffer to raise the pH to 4 to
`8 to form particles, wherein the molarity of the
`neutralized eluate is 100mM or less”
`
`As for step three, Patent Owner does not dispute that Shadle discloses
`
`“neutralizing the eluate from step (2) . . . by addition of a buffer to raise the pH to 4
`
`to 8.” Instead, Patent Owner disputes only the molarity of the neutralized eluate and
`
`whether particles are formed. In so doing, Patent Owner (i) applies an erroneous
`
`inherency standard in disputing the molarity of the neutralized eluate, and (ii)
`
`ignores its admissions in the ʼ289 patent that particles will form under the claimed
`
`conditions. Neither argument has merit.
`
`9
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`
`i.
`
`Shadle’s neutralized eluate inherently has a
`molarity of 100mM or less.
`
`Patent Owner does not dispute Dr. Przybycien’s updated calculations on the
`
`molarity of the neutralized eluate, which show that the total molarity is necessarily
`
`below 100mM. EX1036 ¶41; EX1026 2–3; EX1027 2–3. Nor does Patent Owner
`
`acknowledge its previous admission to the EPO that Shadle’s neutralized eluate has
`
`a calculated total molarity of about 47.2mM—well below the claimed 100mM limit.
`
`EX1006 28; EX1034 ¶43 n.2. Instead Patent Owner contends that a POSA could
`
`use a fifth buffer preparation yielding a molarity higher than 100mM and that the
`
`neutralized eluate would contain so much residual wash buffer that its molarity
`
`would exceed 100mM. Both arguments are mistaken and assume that inherency
`
`requires proof that any other result is “impossible.” Resp. 33.
`
`Buffer preparation. Instead of disputing that the four conventional methods
`
`for preparing Shadle’s citrate buffer result in a neutralized eluate that meets the
`
`molarity limitation, Patent Owner proposes a fifth, purportedly “known method[]”
`
`that “could” have been used to prepare Shadle’s buffer. Resp. 40. But that is not
`
`the law. The law looks to the “normal and usual” way a POSA would practice the
`
`prior art, and the “normal and usual” practice of a POSA would not have used Patent
`
`Owner’s fifth method to practice Shadle. King Pharm., Inc. v. Eon Labs, Inc., 616
`
`F.3d 1267, 1275–76 (Fed. Cir. 2010); EX1036 ¶26–38.
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`10
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`When evaluating inherency, the prior art must be understood according to its
`
`“normal and usual” practice. King Pharm., 616 F.3d at 1275–76; accord Perricone
`
`v. Medicis Pharm. Corp., 432 F.3d 1368, 1383 (Fed. Cir. 2005) (“[T]he discovery
`
`of a new property of the Pereira composition, when used in accordance with its
`
`normal application, is not a sufficient basis for avoiding anticipation.” (emphasis
`
`added)); In re King, 801 F.2d 1324, 1326–27 (Fed. Cir. 1986) (“[T]he law is, and
`
`long has been, that ‘if a previously patented device, in its normal and usual
`
`operation, will perform the function” then the application “will be considered to
`
`have been anticipated by the former patented device.’” (citation omitted; emphasis
`
`added)).
`
`Inherency does not require proof that another result is “impossible.” See
`
`SmithKline Beecham, 403 F.3d at 1343. A result can thus be inherent even if it
`
`theoretically could be avoided. Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342,
`
`1349–50 (Fed. Cir. 1999) (finding inherency even though inherent result could be
`
`avoided by “extraordinary measures”).
`
`In assuming that inherency requires proof that another result is “impossible,”
`
`Patent Owner and its experts thus apply an erroneous legal standard. Resp. 33.
`
`Patent Owner’s cited cases do not hold otherwise. They simply say that “[t]he mere
`
`fact that a certain thing may result from a given set of circumstances is not sufficient
`
`[for inherency].” E.g., Resp. 24, 34. But Petitioner has not just shown that a buffer
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`11
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`“may” have met the neutralized eluate limitations (id.)—Petitioner showed that all
`
`four conventional buffer preparations necessarily do. EX1036 ¶41; EX1034 80:15–
`
`19, 81:7–17, 84:5–85:6, 102:8–23.
`
`Indeed, the prior art consistently shows that citrate buffers were prepared
`
`according to Dr. Przybycien’s four conventional methods. EX1036 ¶30; EX1028,
`
`12; EX1037, 4, EX1015, 8; EX1029, 8; EX1038, 24; EX1014, 172; EX1040, 16;
`
`EX1041, 5. Dr. Cramer’s own publications do too. EX1036 ¶31; EX1030, 3;
`
`EX1031, 3; EX1032, 3; EX1034, 133:6–12, 134:7–15, 135:25–136:5. Tellingly,
`
`none of those publications teach that a 25mM citrate buffer, pH 3.5 should be
`
`prepared using Patent Owner’s fifth preparation (25mM trisodium citrate and HCl).
`
`See id. Nor did Patent Owner even suggest the possibility of that preparation in the
`
`EPO proceedings when distinguishing Shadle.
`
`Consistent with the prior art, a POSA practicing Shadle would not have used
`
`Patent Owner’s fifth preparation (25mM trisodium citrate and HCl) to prepare
`
`Shadle’s ProSep A citrate buffer. EX1036 ¶¶26–38. Even Dr. Cramer refused to
`
`opine that a POSA “would” have used it, insisting only that a POSA “could.”
`
`EX1034 104:7–105:2. Dr. Cramer’s reluctance is unsurprising. As Dr. Przybycien
`
`shows, the starting pH for trisodium citrate is far higher than the target pH for
`
`Shadle’s buffer, and would require an impractical excess of hydrochloric acid to
`
`titrate the pH to Shadle’s target of 3.5. EX1036 ¶28; EX1034 110:7–18 (admitting
`
`12
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`IPR2017-01357
`Patent No. 7,332,289 B2
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`“the pH is high and that you need more acid to bring it down to pH 3.5”). A POSA
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`would instead use a starting solution that was closer in pH to the 3.5 target—e.g.,
`
`monosodium citrate, as Dr. Przybycien proposed. EX1036 ¶28.
`
`A POSA also would have understood from
`
`the cation exchange
`
`chromatography step in Examples 1 and 1A of Shadle that the conductivity of the
`
`citrate buffer solution should be kept as low as possible. EX1036 ¶¶31-35; EX1033,
`
`12–13; EX1046, 532; EX1045, 4–5. This also would have directed a POSA to
`
`prepare the Shadle citrate buffer according to one of the four conventional
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`preparations—not with 25mM trisodium citrate and HCl. EX1036 ¶36.
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`Dr. Cramer cites only a single reference that allegedly taught preparing a
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`citrate buffer as he proposed. Resp. 28 (citing Roth, EX2005). But as Dr.
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`Przybycien explains, a POSA practicing Shadle would not rely on Roth. EX1036,
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`¶29. Roth concerned a field of study and application distinct from the preparative
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`Protein A chromatography of Shadle and the ’289 patent. Id. ¶29. Roth is therefore
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`not an analogous prior art reference. Cf. In re Kahn, 441 F.3d 977, 986–87 (Fed.
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`Cir. 2006). And using Roth’s citrate buffer, which included other excipients, would
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`denature the very antibodies Shadle sought to purify. EX1036 ¶29.
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`Wash buffer. Patent Owner’s only other response is that the neutralized eluate
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`would contain so much wash buffer that its molarity would exceed 100mM. But as
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`Dr. Przybycien shows, Shadle’s neutralized eluate would not contain the large
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`amounts of wash buffer that Patent Owner presumes. EX1036 ¶¶49–53. Indeed,
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`Shadle does not describe any wash buffer collected in the eluate. Instead, it describes
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`the eluate as consisting of concentrated antibody alone. Id. ¶¶44–45. Moreover, a
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`POSA would take steps to minimize the amount of wash buffer in the collected
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`eluate, which a POSA would have viewed as undesirable. EX1036 ¶44.
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`Related EPO proceedings for the EP ’589 and EP ’149 foreign counterpart
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`patents confirm that Patent Owner’s wash buffer argument, which the EPO rejected,
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`lacks merit. EX1036 ¶48; EX1006 6–7, 38–39; EX1043 6, 9–10, 15, 19, 30, 34.4
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`Even if some wash buffer could contaminate the eluate—contamination a POSA
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`would avoid (EX1036 ¶46)—Patent Owner exaggerates its impact. Any
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`contribution of residual wash buffer to the molarity would be minimal and would
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`not increase molarity above 100mM. EX1036 ¶¶49, 52. As Dr. Przybycien explains,
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`Dr. Cramer’s speculation to the contrary is improperly based on either his fifth buffer
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`preparation theory, or an unsupported presumption there would be at least 2.1L of
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`wash buffer contamination. Id. ¶¶48–49. In response, Dr. Przybycien has prepared
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`4 The different proceeding cited by Patent Owner (Resp. 35) is for an unrelated
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`European application that claims priority to a different Japanese application than do
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`the ’289 patent, EP ’589, and EP ’149, and is thus irrelevant. EX1036 ¶48; compare
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`EX1042, 1 to EX1001, 1; EX1004, 1; and EX1019, 1.
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`detailed calculations to demonstrate that any wash buffer contamination in the
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`collected eluate would at most be 0.582L. EX1036 ¶¶50–54; EX1047 5–6. Even
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`that theoretical contamination would not increase the molarity of the neutralized
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`eluate above 100mM. EX1036, ¶50 (explaining preparation no. 1 = 77.93 mM,
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`preparation no. 2 = 65.40 mM, and preparations nos. 3 and 4 = 60.03 mM).
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`Dr. Przybycien’s unrebutted calculations thus confirm that Shadle’s
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`neutralized eluate inherently satisfies step 3’s molarity requirement.
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`ii.
`Recognizing that particles will form whenever the claimed conditions are met,
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`Shadle’s method inherently forms particles.
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`Patent Owner again resorts to claim construction to avoid anticipation. According
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`to Patent Owner, “to form particles” means “becomes clouded.” Resp. 17, 35.
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`Again, however, Patent Owner’s construction is not the broadest reasonable
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`interpretation. Under the proper standard, Shadle discloses the claimed particle
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`formation.
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`First, the broadest reasonable interpretation of “to form particles” does not
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`require the solution to become “clouded,” because a POSA would not equate
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`forming particles with clouding. EX1036 ¶12. To be sure, a clouded solution might
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`indicate that particles have formed, but particles can form in a non-clouded solution
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`too. EX1036 ¶¶11–12; cf. EX1034 97:10–98:18 (admitting clouding can occur
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`without particle formation); EX1035 58:20–59:17 (same). This is especially true
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`when only a few particles form in solution, which a POSA would understand to be
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`covered by the plain or broadest reasonable meaning of “to form particles.” EX1036
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`¶13.
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`If the claims required some greater degree of particle formation, a POSA
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`would expect that requirement to be expressly recited, either as a concentration of
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`particles or an appearance of cloudiness. EX1036 ¶12. Neither requirement is in
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`the claims. And since the ʼ289 patent does not describe how “cloudy” the sample
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`must become (or how to measure its “cloudiness”), Patent Owner’s construction
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`would render the claims indefinite. See Geneva Pharms., Inc. v. GlaxoSmithKline
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`PLC, 349 F.3d 1373, 1384 (Fed. Cir. 2003) (rejecting “a proposed construction”
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`when that “reading of the claim is indefinite”).
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`The actual language of the claims simply says “to form particles,” which a
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`POSA would not equate with clouding. EX1036 ¶12. Patent Owner’s expert, Dr.
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`Koths, admits this. EX1035, 53:24–54:4 (“Q. If a POSA were to see the phrase ‘to
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`form particles,’ would that POSA understand that phrase to mean to produce
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`particles containing DNA to cause the solution to become clouded? A. No.”).5
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`5 Even if clouding were required, Shadle discloses it. Particles form in Shadle, so if
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`Patent Owner is right that particles cause clouding, there is clouding in Shadle. That
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`Shadle “says nothing of clouding” misses the point. Resp. 36. For anticipation,
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`Second, particles necessarily form in Shadle because Shadle discloses the
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`same conditions (i.e., pH, molarity) that the ʼ289 patent admits are sufficient to form
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`particles. EX1036 ¶55. As the Board recognized, there is “no meaningful difference
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`between the conditions sufficient for particle formation set forth in claim 1 and the
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`specification of the ’289 patent, and the conditions disclosed by Shadle in
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`conjunction with the eluate neutralization step.” Dec. Inst. 30. Patent Owner
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`condemns this logic as “hindsight” (Resp. 38), but hindsight is irrelevant to
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`anticipation. Indeed, the Federal Circuit has repeatedly relied on a challenged
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`patent’s disclosure to establish the inherency of a property. See In re Kubin, 561
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`F.3d 1351, 1357 (Fed. Cir. 2009) (“the [inventors’] application itself instructs that
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`[the claimed] … property [is] necessarily present”); In re Kao, 639 F.3d 1057, 1070
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`(Fed. Cir. 2011) (patentee’s own “specification … confirms that the claimed
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`[stability] is an inherent property”).
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`In the two cases cited by Patent Owner (Resp. 38), either the challenger made
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`an unsupported “assumption” about inherency, Crown Operations Int’l, Ltd. v.
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`Shadle does not need to expressly note the presence of particles, or even clouding.
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`Anticipation “does not require that a [POSA] at the time would have recognized the
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`inherent disclosure.” Schering Corp. v. Geneva Pharm., Inc., 339 F.3d 1373, 1377
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`(Fed. Cir. 2003).
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