Trials@uspto.gov
`571-272-7822
`
`
`
`Paper 109
`Entered: April 13, 2022
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES
`BIOTECHNOLOGIES S.A.,
`Petitioner,
`
`v.
`
`NOVO NORDISK HEALTHCARE AG,
`Patent Owner.
`____________
`
`IPR2017-00028
`Patent 9,102,762 B2
`____________
`
`
`Before ERICA A. FRANKLIN, SUSAN L. C. MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`Opinion for the Board filed by Administrative Patent Judge MITCHELL.
`
`Opinion concurring-in-part and dissenting-in-part filed by
`Administrative Patent Judge FRANKLIN.
`
`MITCHELL, Administrative Patent Judge.
`
`
`JUDGMENT
`Determining No Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`Granting-in-Part Patent Owner’s Motion to Exclude
`37 C.F.R. § 42.64
`
`
`
`
`571-272-7822
`
`
`
`Paper 109
`Entered: April 13, 2022
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES
`BIOTECHNOLOGIES S.A.,
`Petitioner,
`
`v.
`
`NOVO NORDISK HEALTHCARE AG,
`Patent Owner.
`____________
`
`IPR2017-00028
`Patent 9,102,762 B2
`____________
`
`
`Before ERICA A. FRANKLIN, SUSAN L. C. MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`Opinion for the Board filed by Administrative Patent Judge MITCHELL.
`
`Opinion concurring-in-part and dissenting-in-part filed by
`Administrative Patent Judge FRANKLIN.
`
`MITCHELL, Administrative Patent Judge.
`
`
`JUDGMENT
`Determining No Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`Granting-in-Part Patent Owner’s Motion to Exclude
`37 C.F.R. § 42.64
`
`
`
`
`
`IPR2017-00028
`Patent 9,102,762 B2
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`I. INTRODUCTION
`Laboratoire Francais du Fractionnement et des Biotechnologies S.A.
`(“LFB” or “Petitioner”) filed a Petition (Paper 1, “Pet.”), requesting
`institution of an inter partes review of claims 1–15 of U.S. Patent No.
`9,102,762 B2 (Ex. 1001, “the ’762 patent”) based on the following ten
`grounds:
`
`Reference(s)1
`
`Tomokiyo, 2 Hill, 3 and
`Burnouf4
`Tomokiyo, Hill, Burnouf, and
`Pedersen6
`Tolo7
`
`Basis
`
`§ 103(a)5
`
`§ 103(a)
`
`Challenged
`Claims
`1, 2, 4–6, and
`10–15
`3 and 7–9
`
`§§ 102(b) or 103(a)
`
`1, 2, 4–7, and
`12–15
`3, 8, and 9
`
`§ 103(a)
`
`Tolo and Pedersen
`
`1 All citations to the references in this Decision refer to the page numbers
`added by Petitioner.
`2 K. Tomokiyo et al., Large-scale production and properties of human
`plasma-derived activated Factor VII concentrate, 84 VOX SANGUINIS 54–64
`(2003) (Ex. 1002, “Tomokiyo”).
`3 Frank G. H. Hill, Guidelines on the selection and use of therapeutic
`products to treat haemophilia and other hereditary bleeding disorders, 9:1
`HAEMOPHILIA 1–23 (2003) (Ex. 1003, “Hill”).
`4 T. Burnouf & M. Radosevich, Nanofiltration of plasma-derived
`biopharmaceutical products, 9:1 HAEMOPHILIA 24–37 (2003) (Ex. 1004,
`“Burnouf”).
`5 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
`(2011) (“AIA”), included revisions to 35 U.S.C. §§ 102 and 103 that became
`effective after the filing of the application that led to the ’762 patent.
`Therefore, we apply the pre-AIA versions of 35 U.S.C. §§ 102 and 103.
`6 Anders H. Pedersen et al., Autoactivation of Human Recombinant
`Coagulation Factor VII, 28:24 BIOCHEMISTRY 9331–36 (1989) (Ex. 1005,
`“Pedersen”).
`7 Tolo et al., WO 99/64441; Dec. 16, 1999 (Ex. 1006, “Tolo”).
`
`
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`Reference(s)1
`
`Tolo and Hill
`Tolo and Mollerup8
`Eibl ’0239 and Mollerup
`
`Basis
`
`§ 103(a)
`§ 103(a)
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`Challenged
`Claims
`10
`11
`1, 2, 4, 6, and
`11–15
`3 and 7–9
`
`5
`
`Eibl ’023, Mollerup, and
`Pedersen
`Eibl ’023, Mollerup, and
`Burnouf
`10
`§ 103(a)
`Eibl ’023, Mollerup, and Hill
`Novo Nordisk Healthcare AG (“Patent Owner”) filed a Preliminary
`Response (Paper 6). We determined, based on the information presented in
`the Petition and Preliminary Response, that there was a reasonable
`likelihood that Petitioner would prevail in challenging claims 1–15 as
`unpatentable under 35 U.S.C. § 103(a). Pursuant to 35 U.S.C. § 314, we
`instituted trial on April 11, 2017, as to those claims of the ’762 patent on
`only the Tomokiyo and the Tolo obviousness grounds. Paper 7, 23
`(“Institution Decision” or Paper 9 (Erratum correcting claim listings)).
`We did not originally include the Tolo anticipation ground within the
`scope of this inter partes review. For this ground, we stated:
`We determine that Petitioner has not demonstrated a
`reasonable likelihood of prevailing with respect to its
`anticipation challenge based on Tolo. In particular, Petitioner
`relies upon Tolo’s Example 3, in which a solution of 0.04
`mg/mL IFN-α was nanofiltered, and we do not find any express
`
`
`8 Inger Mollerup et al., The Use of RP-HPLC for Measuring Activation and
`Cleavage of rFVIIa During Purification, 48 BIOTECHNOLOGY &
`BIOENGINEERING 501–05 (1995) (Ex. 1007, “Mollerup”).
`9 Eibl, WO 2004/011023 A1; Feb. 5, 2004 (Ex. 1008, “Eibl ’023”); Ex. 1009
`(English Translation).
`
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`Patent 9,102,762 B2
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`or inherent teaching in Tolo that the same concentration could
`be used for rFVIIa. In assessing whether a reference
`anticipates, the Board is not permitted to “fill in missing
`limitations simply because a skilled artisan would immediately
`envision them.” Nidec Motor Corp. v. Zhongshan Broad Ocean
`Motor Co. Ltd, No. 2016-1900, 2017 WL 977034, at *3 (Fed.
`Cir. Mar. 14, 2017).
`Inst. Dec. 18.
`
`We also did not include the obviousness grounds based on
`combinations including Eibl ’023 and Mollerup within the scope of this inter
`partes review. Id. at 20–22. For these grounds, we found that Petitioner had
`not demonstrated a reasonable likelihood of prevailing with respect to its
`obviousness challenges based on combinations including Eibl ’023 and
`Mollerup. Id. at 22. We stated that:
`In particular, Petitioner has not explained sufficiently why a
`skilled artisan would have looked to Mollerup’s teachings in
`order to increase the concentration of Factor VIIa to be
`nanofiltered to within the claimed range when Eibl ’023 only
`discloses the limited use of Factor VIIa as part of the
`prothrombin complex or as a separate “activator substance” at a
`much lower concentration. See Ex. 1009, 40–41.
`
`Id.
`Following our institution, Petitioner filed a Motion to Submit
`
`Supplemental Information under 37 C.F.R. § 42.123(a), to which Patent
`Owner filed an Opposition. Paper 17; Paper 19. We denied Petitioner’s
`Motion to Submit Supplemental Information. Paper 22.
`Patent Owner filed a Response to the Petition (Paper 27, “PO Resp.”)
`and Petitioner filed a Reply to Patent Owner’s Response (Paper 40,
`“Reply”). An oral hearing was held on December 12, 2017. The transcript
`of the hearing has been entered into the record. Paper 52 (“Tr.”). We issued
`
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`a Final Written Decision in which we determined that Petitioner had not
`shown by a preponderance of the evidence that any challenged claim of the
`’762 patent was unpatentable under the instituted obviousness grounds.
`Paper 53 at 41.
`After our Final Written Decision was entered, but during the time in
`which Petitioner could file a Request for Rehearing, the United States
`Supreme Court issued its opinion in SAS Institute, Inc. v. Iancu requiring
`that all claims challenged in a petition must be included in any trial. See
`SAS Institute, Inc. v. Iancu, 138 S. Ct. 1348, 1354–60 (2018) (“SAS”)
`(holding that 35 U.S.C. § 318(a) requires a final written decision addressing
`all of the claims challenged in a petition). Shortly thereafter, the Office
`issued guidance stating that “[i]f the PTAB institutes a trial, the PTAB will
`institute on all challenges raised in the petition.” Guidance on the Impact of
`SAS on AIA Trial Proceedings (April 26, 2018) (“Office Guidance”)
`(available at https://www.uspto.gov/patents-application-process/patent-trial-
`and-appeal-board/trials/guidance-impact-sas-aia-trial).
`At the request of Petitioner, we held a conference call with the parties
`and granted Petitioner a three-week extension and more pages for its
`Request for Rehearing “to address all issues, including matters discussed in
`the Final Written Decision, SAS, and the previously non-instituted grounds.”
`Paper 54, 4. In deciding the Request for Rehearing, we stated “we find no
`reason to modify our analysis or conclusions in the FWD [Final Written
`Decision] with respect to the Tomokiyo Grounds,” Paper 60, 6, and “we find
`no reason to modify our analysis or conclusions in the FWD with respect to
`the Tolo Grounds” based on obviousness. Paper 60, 8. In view of SAS and
`the Office Guidance, however, we also stated that “it is appropriate to grant
`
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`rehearing to now institute on the previously non-instituted grounds.” Id. at
`9. Therefore, on August 7, 2018, we instituted a supplemental inter partes
`review focusing on the Tolo anticipation ground and the Eibl ’023 and
`Mollerup combination grounds that we did not consider in our prior Final
`Written Decision. Id. at 11. The parties filed supplemental briefs, and we
`held a supplemental oral hearing addressing these grounds on February 6,
`2019. See Paper 67 (Patent Owner’s Supplemental Rehearing Response);
`Paper 81 (Petitioner’s Supplemental Reply); Paper 101 (Transcript for
`Supplemental Oral Hearing). Patent Owner subsequently filed a Motion to
`Exclude Evidence Under 37 C.F.R. § 42.64. See Paper 85.
`We have jurisdiction under 35 U.S.C. § 6. This Final Written
`Decision is issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73 and
`supplements the initial Final Written Decision by addressing the remaining
`grounds not reached in our initial Final Written Decision. Based on the
`record before us, we conclude that Petitioner has not demonstrated by a
`preponderance of the evidence that claims 1–15 of the ’762 patent are
`unpatentable based on any of the remaining grounds upon which we
`instituted on rehearing in this proceeding.
`
`Related Proceedings
`A.
`As related matters, Petitioner and Patent Owner identify U.S. Patent
`Application No. 15/286,068, filed on October 5, 2016 (pending), and U.S.
`Patent Application No. 14/753,551, filed on June 29, 2015 (abandoned),
`which are continuations of the application that issued as the ’762 patent.
`Pet. 1; Paper 4, 2. Petitioner additionally identifies related proceedings
`
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`Patent 9,102,762 B2
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`concerning counterpart foreign applications in Korea, Japan, Brazil, China,
`and Europe. Pet. 1–2.
`
`The ’762 Patent (Ex. 1001)
`B.
`The ’762 patent issued on August 11, 2015, with Jesper Christensen,
`Erik Halkjaer, Turid Preuss, Thomas Budde Hansen, Lene Vaedele Madsen
`Tomoda, and Nina Johansen as the listed co-inventors. Ex. 1001, (45), (75).
`The ’762 patent claims priority to Provisional Application 60/528,763, filed
`on December 11, 2003, and Danish Application 2003 01775, filed on
`December 1, 2003. Id. at (60), (30).
`The ’762 patent relates to a method for improving the viral safety of
`liquid compositions comprising Factor VII (FVII), a protein involved in the
`blood clotting process. Id. at 1:19–22. Factor VII exists in plasma mainly as
`a single-chain zymogen which is cleaved by FXa into its two-chain,
`activated form, FVIIa. Id. at 1:33–35. Recombinant activated Factor VIIa
`(rFVIIa) has been developed as a pro-haemostatic agent, and the
`administration of rFVIIa offers a rapid and highly effective pro-haemostatic
`response in haemophilic subjects with bleedings, who cannot be treated with
`other coagulation factor products due to antibody formation. Id. at 1:35–41.
`According to the ’762 patent, the purification and handling of FVII
`must be done carefully, due to the possibility for degradation of the
`molecule. Id. at 1:45–46. In particular, the patent explains that FVII and
`FVIIa are susceptible to mechanical degradation by shear forces during
`purification and filtration. Id. at 1:46–49. Further, FVIIa is an active
`proteolytic enzyme that degrades other proteins including FVIIa, wherein
`the degradation of FVIIa mainly involves cleavage in the heavy chain of
`
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`IPR2017-00028
`Patent 9,102,762 B2
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`FVIIa, particularly at amino acids nos. 290 and 315 in the molecule. Id. at
`1:49–54.
`The invention described and claimed in the ’762 patent involves
`subjecting a composition comprising FVIIa to nanofiltration using a
`nanofilter having a pore size of at most 80 nm. Id. at 2:14–32. Example 5
`describes nanofiltration of FVIIa bulk substance with a degree of activation
`(i.e. percentage of FVIIa) being greater than 90% and the amount of
`degradation prior to filtration at 11.9%. Id. at 17:55–63. The resulting
`filtrate had a degradation of 12.3%. Id. at 18:1–7.
`
`Illustrative Claim
`C.
`Petitioner challenges claims 1–15 of the ’762 patent. Independent
`claim 1 is illustrative, and is reproduced below:
`1. A method for removing viruses from a liquid composition
`of recombinant Factor VII comprising one or more Factor
`VII polypeptides having a concentration in the range of
`0.01 to 5 mg/mL, the method comprising subjecting the
`liquid composition to nanofiltration using a nanofilter
`having a pore size of 80 nm or less, wherein 50-100% of
`the Factor VII polypeptides in the composition subjected
`to the nanofilter are in an activated form (FVIIa) prior to
`nanofiltration.
`Ex. 1001, 18:24–31.
`Independent claims 12 and 15 also recite similar methods, but either
`additionally require the step of “combining the composition with a
`detergent” (claim 12) or more narrowly specify a “nanofilter having a pore
`size of 50 nm or less” (claim 15). See id. at 18:61–19:2, 19:9–16.
`Dependent claim 3 depends from claim 2 and further narrows the pH
`range of the liquid composition by requiring “wherein the pH is in the range
`
`
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`IPR2017-00028
`Patent 9,102,762 B2
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`of 8.3–8.7.” Ex. 1001, 18:34–35. Dependent claim 5 depends from claim 1
`set forth above and further requires “wherein the membrane of the nanofilter
`is manufactured from one or more materials selected from the group
`consisting of cuprammonium regenerated cellulose, hydrophilic
`polyvinylidene fluoride (PVDF), composite PVDF, surface modified PVDF,
`and polyether sulfone.” Id. at 18:38–43. Dependent claim 10 also depends
`from claim 1 and further requires “wherein the Factor VII polypeptide(s)
`is/are produced by cell culture in Chinese Hamster Ovary (CHO) cells in a
`medium free from any components of animal origin.” Id. at 18:54–57.
`
`D. Grounds of Unpatentability Addressed in this Final Written
`Decision
`The remaining unpatentability grounds that are discussed in this Final
`Written Decision are:
`Reference(s)
`
`Challenged Claims
`
`Basis
`
`Tolo
`
`Eibl ’023 and Mollerup
`
`Eibl ’023, Mollerup, and
`Pedersen
`Eibl ’023, Mollerup, and
`Burnouf
`Eibl ’023, Mollerup, and Hill
`
`§ 102(b)
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`1, 2, 4–7, and 12–15
`
`1, 2, 4, 6, and 11–15
`
`3 and 7–9
`
`5
`
`10
`
`The Parties’ Declarants
`E.
`Petitioner relies upon the declarations of Dr. Sami Chtourou.
`Ex. 1010 (“Chtourou Decl.”); Ex. 1068 (“Chtourou Reply Decl.”).
`Dr. Chtourou has been the Executive Vice President, Innovation and
`
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`Patent 9,102,762 B2
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`Scientific Affairs at LFB Biotechnologies (an affiliate of Petitioner) since
`2012. Ex. 1010 ¶ 4. He attests that “[s]ince 1987, I have led or contributed
`to the development at LFB of a number of plasma-derived and recombinant
`coagulation factors,” which “include marketed products like plasma-derived
`Factor VIII, Factor IX, Factor XI, Factor VII, Fibrinogen and Von
`Willebrand Factor and other products that are still at preclinical or clinical
`stage, e.g., activated recombinant FVII (‘rFVIIa’).” Id. ¶ 8. He further
`attests that he has had significant experience since the early 1990s with
`respect to the use of nanofiltration to make biotherapeutic products safer. Id.
`¶¶ 9–11.
`Patent Owner relies upon the declarations of Dr. Sriram
`Krishnaswamy and Dr. Gorges Belfort. Ex. 2011 (“Krishnaswamy Decl.”);
`Ex. 2031 (“Krishnaswamy Supp. Decl.”); Ex. 2012 (“Belfort Decl.”). Patent
`Owner’s first declarant, Dr. Krishnaswamy, is a Stokes Investigator at
`Children’s Hospital of Philadelphia, and is also a Professor of Pediatrics, of
`Biochemistry and Biophysics, and of Systems Pharmacology and
`Translational Therapeutics at the University of Pennsylvania. Ex. 2011 ¶ 3.
`His declarations and area of expertise focus on the biochemistry of
`coagulation factors, in particular FVII and FVIIa. Id. ¶ 9. Patent Owner’s
`second declarant, Dr. Belfort, is a chemical and biological engineer with
`more than 45 years of professional experience, and is currently an Institute
`Professor at Rensselaer Polytechnic Institute. Ex. 2012 ¶ 3. His declaration
`and area of expertise focus on membrane technology, nanofiltration, and the
`behavior of proteins at interfaces. Id. ¶ 29.
`
`
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`II. ANALYSIS
`Patent Owner’s Motion to Exclude Evidence
`A.
`Patent Owner moves to exclude the following four exhibits filed by
`Petitioner with its Supplemental Reply (Paper 81): 1) Exhibit 1093 titled
`“Quality of Biotechnology Products: Stability Testing of
`Biotechnological/Biological Products”; 2) Exhibit 1094 titled “Summary
`Basis for Approval” for Patent Owner for Coagulation Factor VIIa
`(Recombinant (rFVIIa)); 3) Exhibit 1095 titled “Transmissible Agents and
`the Safety of Coagulation Factor Concentrates”; and 4) Exhibit 1096, which
`is one of Patent Owner’s published patent applications, WO2004/083421
`A1, titled “Method for the Production of GLA-Residue Containing Serine
`Proteases.” Patent Owner states that:
`These exhibits were not introduced simply to counter
`[Patent Owner’s] arguments in its Supplemental Rehearing
`Response (Paper 67), but rather to address deficiencies in
`[Petitioner’s] prima facie case presented in its Petition. All
`references that are the subject of this motion were publicly
`available at the time of the Petition and could have been
`included in [Petitioner’s] Petition.
`Paper 85, 1.
`
`Petitioner counters that these challenged exhibits were appropriately
`submitted with its Reply because these exhibits confirm its unpatentability
`rationale or its “prima facie case; they do not modify it.” Paper 87, 2.
`Petitioner also asserts that a motion to exclude is an inappropriate vehicle to
`assert that a reply presents new arguments or relies on evidence necessary to
`make out a prima facie case. Paper 87, 1.
`We agree that a motion to exclude is not the appropriate vehicle for
`consideration of whether a party has improperly raised new arguments. Our
`
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`IPR2017-00028
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`Trial Practice Guide delineates between a motion to exclude and a motion to
`strike, indicating that a motion to strike is the preferred mechanism “[i]f a
`party believes that a brief filed by the opposing party raises new issues, is
`accompanied by belatedly presented evidence, or otherwise exceeds the
`proper scope of reply or sur-reply . . . .” See Trial Practice Guide Update 17
`(Aug. 2018); Patent Trial and Appeal Board Consolidated Trial Practice
`Guide 80 (Nov. 2019). 10 Although a motion to exclude is pre-authorized in
`the Scheduling Order, see Paper 64, 4 (Supplemental Scheduling Order), a
`motion to strike is not, and Patent Owner did not request prior authorization
`to file its motion to strike. Petitioner did, however, have an opportunity to
`respond and did so respond to Patent Owner’s contentions that the allegedly
`new evidence and argument exceeded the proper scope of a reply. See Paper
`87, 3–8. Therefore, we find that Petitioner had an appropriate opportunity,
`of which it took advantage, to respond to Patent Owner’s arguments
`regarding the alleged new arguments and evidence. Accordingly, we
`determine that Petitioner is not prejudiced by our consideration of Patent
`Owner’s motion to exclude as, in effect, a motion to strike.
`Petitioner’s Supplemental Reply may only respond to arguments
`raised in P atent Owner’s Supplemental Rehearing Response. See 37 C.F.R. §
`42.23(b). In our Trial Practice Guide, the Board further expounded upon this
`principle stating, “Petitioner may not submit new evidence or argument in
`
`
`10 The version of the Trial Practice Guide that was current at the time that
`Patent Owner’s Motion to Exclude was filed was Trial Practice Guide
`Update (August 2018). The same provisions cited herein have been
`maintained in the current version of the guide, i.e., Patent Trial and Appeal
`Board Trial Practice Guide November 2019 (available at
`https://www.uspto.gov/sites/default/files/documents/tpgnov.pdf).
`
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`reply that it could have presented earlier, e.g. to make out a prima facie case
`of unpatentability.” Patent Trial and Appeal Board Consolidated Trial
`Practice Guide 73 (Nov. 2019) (citing Belden Inc. v. Berk-Tek LLC, 805
`F.3d 1064, 1077–78 (Fed. Cir. 2015)). The Trial Practice Guide further
`explains that “‘Respond,’ in the context of 37 C.F.R. § 42.23(b), does not
`mean proceed in a new direction with a new approach as compared to the
`positions taken in a prior filing,” and “[w]hile replies and sur-replies can
`help crystalize issues for decision, a reply or sur-reply that raises a new issue
`or belatedly presents evidence may not be considered.” Id. at 74.
`“In most cases, the Board is capable of identifying new issues or
`belatedly presented evidence when weighing the evidence at the close of
`trial, and disregarding any new issues or belatedly presented evidence that
`exceeds the proper scope of reply or sur-reply.” Id. at 80. The Board has
`disregarded such inappropriately presented argument and evidence in prior
`cases. See Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821
`F.3d 1359, 1369-70 (Fed. Cir. 2016) (Board did not abuse its discretion in
`refusing to consider reply brief arguments advocating a “new theory” of
`unpatentability under 37 C.F.R. § 42.23(b)); Apple Inc. v. e-Watch, Inc.,
`IPR2015-00412, Paper 50, 44 (PTAB May 6, 2016) (“‘Respond,’ in the
`context of 37 C.F.R. § 42.23(b), does not mean embark in a new direction
`with a new approach as compared to the position originally taken in the
`Petition. Accepting such belatedly presented new arguments would be
`unjust to the Patent Owner and we decline to do so.”). Likewise, we are
`capable here of discerning whether the argument and evidence submitted in
`Petitioner’s Supplemental Reply is appropriate. In this case, however, we
`find that addressing the challenged evidence and corresponding arguments
`
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`first before turning the merits of the unpatentability grounds will help frame
`the issues for consideration before us. Accordingly, we will treat Patent
`Owner’s fully briefed Motion to Exclude as a Motion to Strike and address
`the specific arguments for each challenged exhibit and accompanying
`argument in turn below.
`
`1. Exhibit 1093
`Patent Owner asserts that Petitioner uses Exhibit 1093 to support a
`new argument concerning the definition of the term “Factor VII
`polypeptides” to show that the challenged claims of the ’762 patent that all
`include the term “Factor VII polypeptides” are not entitled to the filing date
`of the priority applications. Paper 85, 4. Patent Owner asserts that this new
`argument was not raised in the Petition or in Dr. Chtourou’s Declaration that
`accompanied the Petition. Id. (citing Ex. 1010 ¶¶ 25–26).
`Petitioner responds:
`EX1093 was offered as reply evidence specifically to
`rebut [Patent Owner’s] and its expert’s arguments, by showing
`that, as of 1998, a POSA [person of ordinary skill in the art]
`would understand the term “conjugated product” to mean “an
`active ingredient . . . bound covalently or noncovalently with a
`carrier.” This exhibit also shows the contrast with the term
`“variants” that Dr. Krishnaswamy agreed are “versions of the
`same protein with different amino acid substitutions.”
`Paper 87, 3–4 (citing Paper 81, 6; Ex. 1092, 175:5–8; Ex. 1093, 219).
`
`We agree with Petitioner that Exhibit 1093 is appropriate evidence
`presented in response to Patent Owner’s argument that the phrase “without
`limitation” in a priority application would encompass conjugates or
`derivatives, not just variants. In addressing the appropriate priority date to
`assign to the claims at issue, Petitioner asserted in its Petition that “[a]s
`
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`IPR2017-00028
`Patent 9,102,762 B2
`
`expressly defined in the ’762 patent, the Board should construe ‘Factor VII
`polypeptides’ to mean Factor VII, Factor VIIa, and variants or derivatives or
`conjugates thereof, including not only alterations to the amino acid
`sequence, but also FVII wherein one or more of its amino acids has been
`chemically and/or enzymatically modified by, e.g., alkylation, glycosylation,
`PEGylation, acylation, ester formation or amide formation . . . .” Pet. 11
`(emphasis added). Based on this definition, Petitioner asserts that the
`priority documents do not provide written description support for the claims
`at issue here because of the inclusion of derivatives and conjugates as well
`as variants as described in the above definition of Factor VII polypeptides.
`Id. at 15, 20. Petitioner presents Exhibit 1093 to show that a conjugate is
`more than a simple variation in the amino acid sequence to rebut Patent
`Owner’s assertion that one of skill in the art would interpret “Factor VII
`polypeptides” as used in the priority documents to include derivatives and
`conjugates. See Paper 81, 6.
`
`Accordingly, we deny Patent Owner’s Motion to Exclude, which we
`treat as a Motion to Strike, as to Exhibit 1093.
`
`2. Exhibits 1094, 1095, and 1096
`Petitioner refers to Exhibits 1094, 1095, and 1096 in its Supplemental
`
`Reply in a section titled “Mindset of a POSA as of December 2004,” see
`Paper 81, 8–11, as well as in support of other substantive patentability
`arguments, see id. at 13–14, 21.
`
`
`
`15
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`IPR2017-00028
`Patent 9,102,762 B2
`
`
`a. Exhibit 1094
`Petitioner relies on Exhibit 1094, purportedly Patent Owner’s
`NovoSeven Summary Basis for Approval dated 1999, to show that in the
`mind of a POSA,
`“a liquid composition of recombinant Factor VII comprising
`one or more Factor VII polypeptides having a concentration in
`the range of 0.01 to 5 mg/mL . . . wherein 50–100% of the
`Factor VII polypeptides in the composition subjected to the
`nanofilter are in an activated form (FVIIa)” was a known
`composition prior to the ’762 patent.
`Paper 81, 8 (quoting Ex. 1094, 1 (“each vial contains 0.6 mg/mL of rVIIa”
`that is known to be “almost 100 percent active”) (citing Ex. 1092, 166:23–
`25, 167:2–16).
`
`Petitioner further relies on Exhibit 1094 to establish that a POSA,
`being aware of NovoSeven’s reconstitution for therapeutic use at a
`concentration of 0.6 mg/ml, “would reasonably infer that the 0.04 mg/ml
`nanofiltration concentration taught in Example 3 of Tolo would be a sensible
`and safe starting concentration for nanofiltering rFVIIa because 0.04 mg/ml
`is 15 times less than the therapeutically used concentration.” Id. at 13
`(emphasis in original). Petitioner concludes from this evidence that “a
`POSA reading Tolo ‘would “at once envisage” the claimed arrangement’ of
`nanofiltering rFVIIa through a 15 nm nanofilter at a concentration of 0.04
`mg/ml in view of Tolo disclosing rFVIIa as a protein suitable for the
`disclosed methods and an exemplary nanofiltering concentration of 0.04
`mg/ml.” Id. at 13.
`Petitioner also relies on Exhibit 1094 to bolster Dr. Chtourou’s
`testimony that “therapeutically used” FVII is essentially 100% activated. Id.
`at 14 (citing Ex. 1094, 3) (stating “[a] vial of NovoSeven contains rFVIIa
`
`
`
`16
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`IPR2017-00028
`Patent 9,102,762 B2
`
`and only ‘trace amounts’ of other proteins”). From this evidence, Petitioner
`concludes that “Tolo’s disclosure of applying its methods to ‘therapeutically
`used’ proteins, including rFVIIa (Ex. 1006, 7:25–34), would cause a POSA
`to ‘at once envisage’ a composition ‘wherein 50–100% of the FVII
`polypeptides in the composition . . . are in an activated form (FVIIa),’ . . . .”
`Id. at 14.
`Patent Owner asserts that with these arguments, Petitioner
`is attempting to introduce new arguments, premised on
`Exhibit 1094, as to what a person of ordinary skill in the art
`[hereinafter, “POSA” or “POSITA”] would have known and
`how they would have interpreted Tolo—the reference upon
`which [Petitioner] bases its anticipation ground—which neither
`[Petitioner], nor its declarant Dr. Chtourou, raised in the
`Petition or accompanying declaration.
`Paper 85, 5. We agree with Patent Owner.
`
`With regard to the Tolo anticipation challenge, Petitioner stated only
`the following in the Petition: “Regarding claim 1, Example 1 of Tolo relates
`to human IFN-α instead of rFVIIa. Nevertheless, Tolo anticipates claim 1
`because Tolo discloses all limitations in a manner that a POSITA would
`immediately recognize and acknowledge as an anticipatory embodiment.”
`Pet. 35. Petitioner relies upon Exhibit 1094 to present a new argument that
`is inappropriately offered at the reply stage to bolster the bare bones analysis
`presented in the Petition as to how Tolo, admittedly involving human IFN-α
`instead of rFVIIa, could be interpreted by a POSA to anticipate the
`challenged claims of the ’762 patent. These arguments and evidence should
`have been offered in the Petition as part of Petitioner’s prima facie case for
`anticipation by Tolo. As such, they improperly exceed the proper scope of a
`reply.
`
`
`
`17
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`Patent 9,102,762 B2
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`Accordingly, we grant Patent Owner’s Motion to Exclude, which we
`
`are treating as a Motion to Strike, as to Exhibit 1094 and will not consider
`Petitioner’s new arguments concerning the exhibit.
`
`b. Exhibit 1095
`In further describing the “mindset of a POSA” as of the purported
`critical date, Petitioner used Exhibit 1095, an article titled “Transmissible
`Agents and the Safety of Coagulation Factor Concentrates,” to explain why
`a POSA would use nanofiltration even with recombinant FVIIa. Paper 81, 9.
`With regard to Exhibit 1095, Petitioner states:
`[A]s of June 2004, a POSA was aware that “[t]he use of
`recombinant clotting factor concentrates does not completely
`eliminate the risk of viral infection” (EX1095, 7); accordingly,
`a POSA knew that rFVIIa carried viral risk and knew that
`nanofiltration, as well as other purification processes (e.g.,
`chromatography), were methods of removing viruses from
`coagulation factor compositions (id., 9).
`Paper 81, 9.
`
`Petitioner also uses Exhibit 1095 to bolster its rationale to combine
`Eibl ’023 and Mollerup as combining complementary techniques. Id. at 21.
`Petitioner explains:
`Novo argues there is “no reason to combine Eibl and
`Mollerup other than hindsight” (Paper 67, 18), but in reality
`combining Eibl and Mollerup is not hindsight because both
`references relate to the preparation of virus-safe coagulation
`products. At least as of June 2004, it was recognized that one
`of the primary ways viruses are removed from biological
`compositions is through “[i]ncidental removal during
`purification of [the] protein of interest,” including during
`“chromatographic separation” (EX1095, 9), such as the
`chromatographic purification disclosed by Mollerup.
`Moreover, it was advised that nanofiltration should be used “as
`a complement” to other virus removal techniques. EX1003, 1.
`
`
`
`18
`
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`Accordingly, as of December 1, 2004, a POSA would have
`known – without using hindsight – that Eibl and Mollerup
`disclose combinable complementary techniques.
`Paper 81, 21.
`We agree with Patent Owner that Petitioner is attempting
`inappropriately to introduce new argument and evidence at the reply stage to
`support its rationale to combine Eibl ’023 and Mollerup. See Paper 85, 5–6.
`In the Petition, Petitioner asserted that a POSA would combine the teachings
`of Eibl ’023 and Mollerup to increase throughput for commercial
`production. Pet. 48–49. Specifically, Petitioner stated:
`A POSITA would have been motivated to modify the
`method of Eibl ’023 by using the rFVIIa solutions at
`concentrations of 0.8 mg/ml and 1.4 mg/ml as disclosed in
`Mollerup to increase the rate of purification. For example, a
`POSITA would have been motivated to increase the
`concentration of FVII/FVIIa to increase throughput for
`commercial production. Ex. 1010 at ¶¶ 60, 102. A POSITA
`would have had a reasonable expectation of success in doing so,
`because Mollerup taught that even at concentrations of 0.8 and
`1.4 mg/ml, “the autolytic reaction rate of rFVIIa in this system
`is low.” Ex. 1007 at 3, right column, last three lines and 4,
`Fig. 6; see also Ex. 1010 at ¶¶ 115-116.
`Pet. 48–49.
`
`In discussing the reason to combine the teachings of Eibl ’023 and
`Mollerup in the Petition, Petitioner did not mention th
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