By:
`
`John A. Bauer
`Nelson Mullins Riley & Scarborough LLP
`280 Park Avenue, 15th Floor West
`New York, NY 10017
`(646) 428-2615 (telephone)
`(646) 428-2610 (facsimile)
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`GENOME & COMPANY,
`Petitioner
`
`v.
`
`THE UNIVERSITY OF CHICAGO,
`Patent Owner
`___________________
`
`Case No. PGR2019-00002
`U.S. Patent 9,855,302 B2
`___________________
`
`
`PETITIONER’S OPPOSITION TO PATENT OWNER’S MOTION TO
`EXCLUDE EVIDENCE
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`TABLE OF CONTENTS
`
`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`Page
`
`TABLE OF AUTHORITIES ................................................................................. ii
`
`TABLE OF EXHIBITS ........................................................................................ iv
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................ 1
`
`ARGUMENT................................................................................................ 2
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`G.
`
`H.
`
`I.
`
`J.
`
`K.
`
`L.
`
`Exhibit 1002 (First Declaration of Dr. Braun) ..................................... 2
`
`Exhibit 1043 (Second Declaration of Dr. Braun) ................................ 4
`
`Exhibit 1017 (O’Mahony) ................................................................... 5
`
`Exhibit 2005 (Sivan) ........................................................................... 7
`
`Exhibit 1044 (Sanchez) ....................................................................... 8
`
`Exhibit 1028 (Thungappa) .................................................................. 9
`
`Exhibit 1041 (Fares) ......................................................................... 10
`
`Exhibit 1032 (Kaiser) ........................................................................ 10
`
`Exhibit 1033 (Snyder) ....................................................................... 11
`
`Exhibit 1057 (Weber) ....................................................................... 12
`
`Exhibit 1023 (Targeted Cancer Therapies) ....................................... 12
`
`Exhibit 1059 (Schultz Declaration) ................................................... 14
`
`III. CONCLUSION .......................................................................................... 14
`
`
`
`
`
`
`i
`
`

`

`TABLE OF AUTHORITIES
`
`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
` Page(s)
`
`Cases
`
`Ariosa Diagnostics v. Verinata Health, Inc., 805 F.3d 1359 (Fed. Cir. 2015) ....... 13
`
`Arista Records LLC v. Usenet.com, Inc.,
`608 F. Supp. 2d 409 (S.D.N.Y. 2009) ............................................................ 2-4
`
`Celltrion, Inc. v. Genentech, Inc., IPR2017-01374,
`Paper 85 (PTAB Nov. 29, 2018) ...................................................................... 13
`
`Ericsson Inc. v. Intellectual Ventures I, LLC, IPR2014-01149,
`Paper 68 (PTAB Dec. 9, 2015) ........................................................................ 13
`
`Fox Factory, Inc. v. SRAM, LLC, IPR2016-01876,
`Paper 59 (PTAB Apr. 2, 2018) ......................................................................... 12
`
`Incyte Corp. v. Concert Pharms., Inc., IPR2017-01256,
`Paper 119 (PTAB Apr. 8, 2019) ....................................................................... 10
`
`Intex Rec. Corp. v. Team Worldwide Corp., IPR2018-00859,
`Paper 128 (PTAB Oct. 21, 2019) ....................................................................... 5
`
`Nichia Corp. v. Emcore Corp., IPR2012-00005,
`Paper 68 (PTAB Feb. 11, 2014) ................................................... 2, 5, 10, 13, 14
`
`Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc) .......................... 8
`
`Randall Mfg. v. Rea, 733 F.3d 1355 (Fed. Cir. 2013) .............................................. 8
`
`S.E.C. v. Guenthner, 395 F. Supp. 2d 835 (D. Neb. 2005) .................... 5, 10, 13, 14
`
`Wojciak v. Nishiyama, 61 USPQ2d 1576 (B.P.A.I. 2001) ....................................... 6
`
`Yeda Research v. Mylan Pharm. Inc., 906 F.3d 1031 (Fed. Cir. 2018) ........... passim
`
`Rules
`
`37 C.F.R. § 42.65(a) ............................................................................................... 5
`
`ii
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`Other Authorities
`
`77 Fed. Reg. 6879 (February 9, 2012) ..................................................................... 6
`
`
`
`
`
`iii
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`TABLE OF EXHIBITS
`
`
`Previously Filed Exhibits
`
`
`Exhibit Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`U.S. Patent No. 9,855,302
`
`First Declaration of Jonathan Braun, M.D., Ph.D.
`
`U.S. Publication No. 2009/027401 to Korman et al.
`
`Jagveer Singh et al., Bifidobacterium longum, a lactic acid-producing
`intestinal bacterium inhibits colon cancer and modulated the
`intermediate biomarkers of colon carcinogenesis, Carcinogenesis
`(1997)
`
`Ping Dong et al., The role of intestinal Bifidobacteria on immune
`system development in young rats, Early Human Development (2010)
`
`Suzanne L. Topalian et al., Survival, Durable Tumor Remission, and
`Long-Term Safety in Patients With Advanced Melanoma Receiving
`Nivolumab, Journal of Clinical Oncology (Apr. 1, 2014)
`
`Yoshinori Kohwi et al., Antitumor effect of Bifidobacterium Infantis in
`Mice, Gann (Oct. 1978)
`
`Dheeraj Mohania et al., Modulation of expression of Programmed
`Death-1 by administration of probiotic Dahi in DMH-induced
`colorectal carcinogenesis in rats, Acta Biomed (2013)
`
`U.S. Publication No. 2010/0028449 to Prakash et al.
`
`D. van der waaij et al., The Influence of antibiotics on gut
`colonizastion, Journal of Antimicrobial Chemotherapy (1986)
`
`Do Kyung Lee et al., Anti-proliferative effects of Bifidobacterium
`adolescentis SPM0212 extract on human colon cancer cell lines, BMC
`Cancer, (Oct. 2008)
`
`U.S. Provisional Patent Application No. 62/169,112
`
`U.S. Provisional Patent Application No. 62/248,741
`
`File History of U.S. Patent No. 9,855,302
`
`File History of U.S. Patent Application No. 15/718,735
`
`Elad Sharon et al, Immune checkpoints in cancer clinical trials,
`Chinese Journal of Cancer (2014)
`
`1017
`
`U.S. Publication No. 2012/0276143 to O’Mahony et al.
`
`iv
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`Exhibit Description
`
`U.S. Publication No. 2007/0258953 to Duncan et al.
`1018
`1019 Mosby’s Medical dictionary 8th ed. (2009)
`Dorland’s Illustrated Med Diction 31st ed. (2007)
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`Cyriac Kandoth et al., Mutational landscape and significance across
`12 major cancer types, Nature (Oct. 17, 2013)
`
`Shashank Kumar et al., Drug Targets for Cancer Treatment: An
`Overview, Medicinal Chemistry (2015)
`
`Targeted Cancer Therapies, National Cancer Institute,
`https://www.cancer.gov/about-cancer/treatment/types/targeted-
`therapies/targeted-therapies-factsheet
`
`Andrew M. Scott et al., Monoclonal antibodies in cancer therapy,
`Cancer Immunity Commentary (May 1, 2012)
`
`Henrique Neves et al., Recent advances in the field of anti-cancer
`immunotherapy, BBA Clinical (2015)
`
`Drew M. Pardoll, The blockade of immune checkpoints in cancer
`immunotherapy, Nature Reviews Cancer (Apr. 2012)
`
`Joseph A. DiMasi et al., Economics of New Oncology Drug
`Development, Journal of Clinical Oncology (Jan. 10, 2007)
`
`Satheesh Thungappa et al., Immune checkpoint inhibitors in lung
`cancer: the holy grail has not yet been found…, ESMO Open (2017)
`
`Naiyer A. Rizvi et al., Mutational landscape determines sensitivity to
`PD-1 blockade in non-small cell lung cancer, Science (2015)
`
`Julie R. Brahmer et al., Phase I Study-Agent Anti-Programmed Death-
`1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity,
`Pharmacodynamics, and Immunologic Correlates, Journal of Clinical
`Oncology (July 1, 2010)
`
`D. T. Le et al., PD-1 Blockade in Tumors with Mismatch-Repair
`Deficiency, The New England Journal of Medicine (2015)
`
`Jocelyn Kaiser, Why a powerful cancer drug only helps some patients,
`Science(Mar. 12, 2015)
`
`Alexandra Snyder et al., Genetic basis for clinical response to CTLA-4
`blockade in melanoma, The New England Journal of Medicine (2014)
`
`Ivaylo I. Ivanov et al. Intestinal commensal microbes as immune
`modulators,” Cell Host & Microbe (2012)
`
`v
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`Exhibit Description
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`Lora V. Hooper et al., Interactions between the microbiota and the
`immune system” Science (June 8, 2012)
`
`Kenya Honda et al., The Microbiome in Infection Disease and
`Inflammation, Annual Review of Immunology (2012)
`
`Paul B. Eckburg et al., Diversity of the human intestinal microbial
`flora, Science (June 10, 2005)
`
`Patricia Lopez et al., Distinct Bifidobacterium strains drive different
`immune responses in vitro, International Journal of Food Microbiology
`(2010)
`
`U.S. Publication No. 2008/0193373 to Stritzker et al.
`
`Bandaru S. Reddy et al., Inhibitory effect of Bifidobacterium longum
`on Colon, Mammary, and Liver Carcinogenesis Induced by 2-Amino-
`3-methylimidazo[4,5-f]quinolone, a Food Mutagen,” Cancer Research
`(Sept. 1, 1993)
`
`Charlene M. Fares et al., Mechanisms of Resistance to Immune
`Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunity Not
`Work for All Patients?, American Society of Clinical Oncology
`Educational Book, 39:147-164 (May 17, 2019)
`
`Transcript of Deposition of Sridhar Mani, M.D., on September 26,
`2019 (141 pages)
`
`Second Declaration of Jonathan Braun, M.D., Ph.D.
`
`Borja Sánchez et al., The Effects of Bifidobacterium breve on Immune
`Mediators and Proteome of HT29 Cells Monolayers, BioMed
`Research International, 2015 (Article ID 479140):1-6 (2015)
`
`Vanessa K. Ridaura et al., Gut Microbiota from Twins Discordant for
`Obesity Modulate Metabolism in Mice, Science, 341:1079, 1241214
`(2013)
`
`Gavin P. Dunn et al., The Three Es of Cancer Immunoediting, Annu.
`Rev. Immunol., 22:329-360 (2004)
`
`Patrick Blanco et al., Dendritic cells and cytokines in human
`inflammatory and autoimmune diseases, Cytokine & Growth Factor
`Reviews, 19 (Issue 1):41-52 (2008)
`
`1048
`
`Reza Aghebati Maleki et al., Effects of some natural
`immunomodulatory compounds in combination with thalidomide on
`
`vi
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`Exhibit Description
`
`survival rate and tumor size in fibrosarcoma-bearing mice, Advanced
`Pharmaceutical Bulletin, 4, Suppl 1:465-470 (2014)
`
`1049
`
`Blanda Di Luccia et al., Lactobacillus gasseri SF1183 Affects
`Intestinal Epithelial Cell Survival and Growth, PLoS ONE,
`8(7):e69102 (2013)
`
`1050 Mario Uccello et al., Potential role of probiotics on colorectal cancer
`prevention, BMC Surgery, 12 (Suppl 1):S35(1-8) (2012)
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`Yu-Jie Zhang et al., Impacts of Gut Bacteria on Human Health and
`Diseases, Int. J. Mol. Sci., 16:7493-7519 (2015)
`
`Natarajan Sithranga Boopathy et al., Effect of Mangrove Tea Extract
`from Ceriops decandra (Griff.) Ding Hou. on Salivary Bacterial Flora
`of DMBA Induced Hamster Buccal Pouch Carcinoma, Indian Journal
`of Microbiology, 51(3):338-344 (2011)
`
`Yoram Bouhnik et al., Four-week short chain fructo-oligosaccharides
`ingestion leads to increasing fecal bifidobacteria and cholesterol
`excretion in healthy elderly volunteers, Nutrition Journal, 6(42):1-7
`pages (2007)
`
`Yan Yin et al., Therapeutic efficacy of Bifidobacterium longum-
`mediated human interleukin-2 with endostatin or TRAIL in
`transplanted tumors in mice, Experimental and Therapeutic Medicine,
`3:481-486 (2012)
`
`Rakesh K. Jain et al., Can engineered bacteria help control cancer?,
`PNAS, 98(26):14748-14750 (2001)
`
`I. Brook, Isolation of non-sporing anaerobic rods from infections in
`children, J Med Microbiol., 45(1):21-26 (1996)
`
`Emmanuelle Weber et al., Bifidobacterium Species Bacteremia: Risk
`Factors in Adults and Infants, Clin Infect Dis., 61(3):482-484 (2015)
`
`Hilde Cheroutre et al., The light and dark sides of intestinal
`intraepithelial lymphocytes, Nature Reviews Immunology, 11(7):445-
`456 (2011)
`
`1059
`
`Declaration of Andrew Schultz
`
`
`
`
`
`
`vii
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`New Exhibits
`
`
`Exhibit Description
`
`1060
`
`1061
`
`
`
`Declaration of Reeves Gillis
`
`Exhibit W to the Declaration of Reeves Gillis, printout from the
`European Society for Medical Oncology webpage,
`https://esmoopen.bmj.com/content/2/1/e000162.info
`
`viii
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`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`I.
`
`INTRODUCTION
`
`Petitioner hereby opposes Patent Owner’s (“PO”) Motion to Exclude
`
`Evidence (“Mot.”). Petitioner submits herewith Exhibits 1060 and 1061, which
`
`were previously served on PO in accordance with 37 C.F.R. § 42.64(2).
`
`PO’s motion is utterly without merit. For example, PO seeks to exclude
`
`portions of Petitioner’s expert declarations on the basis of hearsay, notwithstanding
`
`that for each declaration, Petitioner’s expert testified that “all of the opinions and
`
`conclusions found in this declaration are my own.” PO also attempts to exclude
`
`peer-reviewed printed publications expressly addressing the teachings of the cited
`
`prior art on the basis that these publications occurred after the effective filing date
`
`of the ‘302 patent. The law, however, is unequivocal – it is entirely proper for a
`
`post-filing date reference to show “how one with ordinary skill in the art would
`
`have understood a prior art disclosure.” Even more incredulously, PO seeks to
`
`exclude statements of a post-filing date reference PO itself introduced into
`
`evidence and which is co-authored by all three ‘302 patent inventors. Stripped to
`
`its core, PO is simply seeking – without legal basis – to exclude highly damaging
`
`documentation and testimony.
`
`In addition, policy considerations also weigh in favor of maintaining a
`
`complete record: “There is a strong public policy for making all information filed
`
`in a nonjury, quasi-judicial administrative proceeding available to the public,
`
`1
`
`

`

`especially in an [AIA proceeding] which determines the patentability of claims in
`
`an issued patent.” Nichia Corp. v. Emcore Corp., IPR2012-00005, Paper 68 at 59
`
`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`(Feb. 11, 2014).
`
`II. ARGUMENT
`
`A. Exhibit 1002 (First Declaration of Dr. Braun)
`
`PO moves to exclude selected paragraphs of Dr. Braun’s first declaration
`
`(Exhibit 1002) under FRE 802 as inadmissible hearsay and under FRE 702/703 for
`
`not meeting the standard for an expert to rely on hearsay. Improperly framing this
`
`as a question of admissibility, PO alleges that similarities between various
`
`passages of Exhibit 1002 and the Petition “suggest[] that Dr. Braun’s testimony
`
`was provided to him by Petitioner...” and that Dr. Braun “simply transmit[ed] that
`
`hearsay” without “applying any expertise whatsoever.” Mot. at p. 3.
`
`There is no such suggestion in the record, and it is reckless for PO to make
`
`such accusations based on the Petition’s heavy reliance on Dr. Braun’s declaration.
`
`Without any factual basis, PO’s motion attempts to draw parallels to the inapposite
`
`holding of Arista Records LLC v. Usenet.com, Inc., 608 F. Supp. 2d 409, 424-29
`
`(S.D.N.Y. 2009). In Arista Records, the district court prevented the consideration
`
`of an expert’s testimony that regurgitated specific representations provided by the
`
`expert’s benefactor and for which the expert lacked both education and experience.
`
`Indeed, the expert in Arista Records conceded that “he does not know the first
`
`2
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`thing” about the particular issues upon which the excluded opinions were based.
`
`608 F. Supp. 2d at 424.
`
`In the instant proceeding, however, Dr. Braun—who currently serves as
`
`Professor and Chair of Pathology and Laboratory Medicine at the UCLA David
`
`Geffen School of Medicine and has “more than 33 years of practicing, researching,
`
`and teaching oncology, pathology, microbiology and immunology (Ex. 1002 at
`
`¶¶4,7)—testified that he has “personal knowledge of the facts and opinions set
`
`forth in this declaration” and that “the opinions and conclusions found in this
`
`declaration are my own.” Id. at ¶1.
`
`Despite these unequivocal statements by Dr. Braun, PO’s motion suggests
`
`that various portions of Exhibit 1002 are inadmissible “attorney argument” merely
`
`because Dr. Braun discussed his testimony with Petitioner’s counsel prior to an
`
`initial written draft of the declaration being prepared by counsel on the basis of
`
`these discussions, and because Dr. Braun “reviewed” and “revised” this testimony
`
`until he believed it to be complete.1 Mot. at 4. Tellingly, PO’s motion fails to cite
`
`Dr. Braun’s affirmation that he had not seen the petition prior to completing his
`
`
`1 PO’s motion only cites to page 90, line 25 through page 91, line 23 of the
`
`transcript of Dr. Braun’s first deposition (Ex. 2033). Mot. at 4.
`
`3
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`declaration and that “all the opinions stated in that declaration” and “all the
`
`assertions in that declaration” were his own. Ex. 2003 at 91:24-92:10.
`
`Unlike the expert whose testimony was disqualified in Arista Records, Dr.
`
`Braun has affirmed that Exhibit 1002 is based on his own extensive knowledge and
`
`experience. And it is this extensive experience in the field that provided him with
`
`the “scientific, technical, or other specialized knowledge” as required by FRE
`
`702(a) to opine on the ‘302 patent’s disclosure, the prior art, and other issues in
`
`this proceeding from the perspective of a POSITA. Ex. 1002 at ¶3.
`
`For at least the above reasons, PO’s motion to exclude should be denied with
`
`respect to Exhibit 1002.
`
`B.
`
`Exhibit 1043 (Second Declaration of Dr. Braun)
`
`PO moves to exclude paragraphs 41, 43, 44, 57-66, 72-85, and 87-98 of Dr.
`
`Braun’s second declaration (Ex. 1043) as inadmissible hearsay and for not meeting
`
`the standard for an expert to rely on hearsay. For the same reasons discussed
`
`above in Section A, PO’s motion with respect to these paragraphs of Exhibit 1043
`
`should be denied.
`
`PO also alleges that because paragraphs 1-9, 14, 20-22, 57, 58, 63, 64, 72,
`
`77, 78, 81, 84, 87, 93, 94, and 99 of Exhibit 1043 are not specifically identified by
`
`paragraph number in the Reply, they should be excluded under FRE 401/402. In
`
`the interest of public policy, the complete, comprehensive testimony of Dr. Braun
`
`4
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`(including any uncited portion that further supports Dr. Braun’s conclusions cited
`
`in Petitioner’s Reply) should be maintained in the record. See e.g., Nichia Corp.,
`
`IPR2012-00005, Paper 68 at 59; S.E.C. v. Guenthner, 395 F. Supp. 2d 835, 842 n.3
`
`(D. Neb. 2005); see also 37 C.F.R. § 42.65(a) (“[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.”).
`
`Finally, PO moves to exclude paragraphs 23-30, 31-42, 45-51, and 67-71 of
`
`Exhibit 1043 as an impermissible incorporation-by-reference under 37 C.F.R.
`
`§ 42.6(a)(3). A motion to exclude evidence, however, is not the proper vehicle to
`
`address incorporation by reference. Intex Rec. Corp. v. Team Worldwide Corp.,
`
`IPR2018-00859, Paper 128 at 57-58 (Oct. 21, 2019). As PO fails to provide any
`
`basis under the Federal Rules of Evidence as to why portions of Dr. Braun’s
`
`declaration are inadmissible, PO’s motion with respect to these paragraphs should
`
`also be denied.
`
`C. Exhibit 1017 (O’Mahony)
`
`PO moves to exclude Exhibit 1017 as inadmissible under 37 C.F.R.
`
`§ 42.61(c) “to the extent Petitioner relies on Ex. 1017 as evidence of the truth of
`
`the data reported therein.” Mot. at 5. PO’s argument to strike Petitioner’s
`
`arguments regarding Exhibit 1017 has no merit and should be denied.
`
`5
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`PO alleges that “Petitioner argues that one of ordinary skill in the art would
`
`have known from O’Mahony that certain things were true.” Mot. at 6. However,
`
`Rule 42.61(c) does not apply to any of those “certain things” that PO seeks to
`
`strike. See 77 Federal Register 6879, 6889 (February 9, 2012); see also Wojciak v.
`
`Nishiyama, 61 USPQ2d 1576, 1580 (B.P.A.I. 2001). Petitioner does not argue, for
`
`example, that the experiments described in paragraphs [0100]-[0102] of O’Mahony
`
`were actually carried out as described. Nor does Petitioner argue that the data
`
`reported by O’Mahony in paragraphs [0103]-[0109] was, in fact, the data resulting
`
`from those experiments. Rather, Petitioner’s arguments to which PO object are
`
`directed to what a POSITA would have understood from the data as reported by
`
`O’Mahony.
`
`As such, paragraphs [0103]-[0109] are “admissible…to prove what the
`
`specification or patent describes” (77 Fed. Reg. at 6889): that a POSITA would
`
`have understood O’Mahony to describe the properties of B. longum to be “strain
`
`specific,” and that B. longum strain 1714 exhibited immunosuppressive properties
`
`and B. longum strain UCC356624 exhibited immunostimulatory properties.
`
`For at least the above reasons, PO’s motion to exclude should be denied with
`
`respect to Exhibit 1017.
`
`6
`
`

`

`PGR2019-00002
`U.S. Patent 9,855,302 B2
`
`D. Exhibit 2005 (Sivan)
`
`Ex. 2005 was introduced by Patent Owner and is co-authored by the
`
`inventors of the ‘302 patent. Nevertheless, PO seeks to exclude Exhibit 2005
`
`under FRE 401/402 as lacking relevance. Such a request is not the proper subject
`
`of a motion to exclude and should be denied for at least this reason.
`
`Moreover, as argued in Petitioner’s Reply, Exhibit 2005 is highly relevant,
`
`substantially contemporaneous evidence that a POSITA would have interpreted
`
`Dong to describe B. longum as immunostimulatory. See Paper 23 at 9-10. In this
`
`PGR initiated in 2019, PO alleges that a POSITA would not have understood Dong
`
`to disclose immunostimulatory effects due to Dong’s questionable methodology.
`
`See e.g., Paper 17 at 52 (“POSA can’t draw conclusions due to Dong’s flawed
`
`methodology”). However, the inventors of the ‘302 patent and authors of Exhibit
`
`2005 cited Dong as describing B. longum being immunostimulatory, i.e.,
`
`“[s]timulatory interactions between bifidobacteria [longum] and the host immune
`
`system, including those associated with interferon-γ (IFNγ) have been described
`
`previously.” Ex. 2005, 1085. That Exhibit 2005 is published after the priority date
`
`of the ‘302 Patent is of no moment. It is well established that a post filing date
`
`reference is relevant to show “how one with ordinary skill in the art would have
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`understood a prior art disclosure.” Yeda Research v. Mylan Pharm. Inc., 906 F.3d
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`1031, 1041 (Fed. Cir. 2018). Indeed, such documentary evidence is more credible
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`7
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`than PO’s litigation induced opinion of its expert. See Randall Mfg. v. Rea, 733
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`F.3d 1355, 1362-63 (Fed. Cir. 2013); Phillips v. AWH Corp., 415 F.3d 1303, 1317-
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`18 (Fed. Cir. 2005) (en banc).
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`E.
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`Exhibit 1044 (Sanchez)
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`PO’s motion to exclude Exhibit 1044 under FRE 401/402 should similarly
`
`be denied. PO alleges that the copyright date of 2015 on Exhibit 1044 is
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`insufficient to establish that it was published prior to June 1, 2015. Mot. at 12-13.
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`As discussed above, however, there is no such requirement under FRE 401/402
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`when the post-filing date reference is introduced for the purpose of showing “how
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`one with ordinary skill in the art would have understood a prior art disclosure.”
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`Yeda Research, 906 F.3d at 1041. And that is precisely the purpose of Petitioner’s
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`introduction of and reliance on Ex. 1044.
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`Exhibit 1044 (Sanchez) was submitted with Petitioner’s Reply as further
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`evidence that a POSITA would understand that Exhibit 1038 (Lopez) reports
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`strain-specific effects induced by Bifidobacterium. See Paper 23 at 10-11. In
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`particular, Sanchez was relied on to dispute PO’s characterizations and its
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`declarant’s testimony regarding Lopez. Accordingly, like Ex. 2005, Exhibit 1044
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`is not only admissible, but highly relevant. It should not be excluded.
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`8
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`F.
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`Exhibit 1028 (Thungappa)
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`PO’s motion to exclude Exhibit 1028 should also be denied. With respect to
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`U.S. Patent 9,855,302 B2
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`PO’s objection to Exhibit 1028 as lacking authentication, Petitioner notes that
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`supplemental evidence in the form of Exhibits 1060 and 1061 were previously
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`served on PO in accordance with 37 C.F.R. § 42.64(2). Exhibit 1060 is the
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`declaration from an analyst in the Research Services Department of the
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`undersigned counsel’s previous firm indicating that Exhibit 1028 is a true and
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`correct copy of the article published by the ESMO in March 2017. See Ex. 1060 at
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`¶¶2, 23. Exhibit 1061 is an additional printout from the EMSO Open webpage
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`indicating that Exhibit 1028 was published on March 27, 2017. See also Ex. 1060
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`at ¶24. PO’s motion to exclude Exhibit 1028 as lacking authentication should be
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`denied based on the supplemental evidence filed herewith, as well as indicia within
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`Exhibit 1028 itself.
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`PO additionally moves to exclude Exhibit 1028 because the “document did
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`not predate the effective filing date in this case.” Mot. at 8. As with Exhibits 2005
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`and 1044 discussed above, Exhibit 1028’s post-filing publication date does not
`
`detract from its relevance. This article, entitled “Immune checkpoint inhibitors in
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`lung cancer: the holy grail has not yet been found….”, indicates that immune CPIs
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`had only been shown in a limited numbers of cancers and for a limited subset of
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`patients as of its publication in 2017. See Pet. at 27. If the effectiveness of CPIs
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`9
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`remained in doubt as of 2017, then Exhibit 1028 is surely relevant regarding the
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`expectations of a POSITA as of the filing date of the ‘302 patent. See Yeda
`
`Research, 906 F.3d at 1041; see also Incyte Corp. v. Concert Pharms., Inc.,
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`IPR2017-01256, Paper 119, 41 (Apr. 8, 2019).
`
`G. Exhibit 1041 (Fares)
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`PO’s motion to exclude Exhibit 1041, a 2019 ASCO reference, should be
`
`denied. Exhibit 1041 was presented to PO’s declarant at his deposition and asked
`
`whether he agreed with the statement, “However, despite these promising long
`
`term responses, the majority of patients fail to respond to immune checkpoint
`
`blockade demonstrating primary resistance.” PO’s declarant refused to provide an
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`answer. See Ex. 1042 at 39:7-19. Petitioner submits that a complete record of Dr.
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`Mani’s testimony should be maintained for policy reasons as well as to judge Dr.
`
`Mani’s credibility. Further, the Board is well-positioned to assign appropriate
`
`weight to Exhibit 1041 without resorting to formal exclusion. See e.g., Nichia
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`Corp., IPR2012-00005, Paper 68 at 59; S.E.C. v. Guenthner, 395 F. Supp. 2d at
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`842 n.3.
`
`H. Exhibit 1032 (Kaiser)
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`PO’s motion to exclude Exhibit 1032 should be denied. With respect to the
`
`alleged lack of authentication, Exhibit 1032 on its face establishes a publication
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`10
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`date of March 12, 2015, which is further confirmed by the supplemental evidence
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`submitted herewith. See Ex. 1060 at ¶25.
`
`PO’s motion to exclude Exhibit 1032 under FRE 401/402 should also be
`
`denied. PO again incorrectly argues that this exhibit should be excluded merely
`
`because the “document did not predate the effective filing date in this case.” Mot.
`
`at 8. However, even if an August 2018 date for Exhibit 1032 were accepted, this
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`article would remain relevant for Petitioner’s proposition that the effectiveness of
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`CPIs as cancer therapy is still in doubt:
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`Clinical studies showed that PD-1 inhibitors shrink tumors in only
`
`about 20-30% of lung cancer patients. See Kaiser, “Why a powerful
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`cancer drug only helps some patients,” Science. doi:10.1126/
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`science.aab0310, March 12, 2015. (Ex. 1032)….The conclusion from
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`these types of studies is that not all patients with a particular cancer
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`respond to a particular immune checkpoint inhibitor….In sum, the use
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`of immune checkpoint inhibitors to treat cancers in humans was highly
`
`unpredictable as of June 2015 and is still so today.
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`Pet. at 28-29 (emphasis added); see also Yeda Research, 906 F.3d at 1041.
`
`I.
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`Exhibit 1033 (Snyder)
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`PO’s motion to exclude Exhibit 1033 under FRE 401/402 should be denied.
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`PO’s motion to exclude is based on an allegation that Exhibit 1033, indicated as
`
`being originally published on November 19, 2014, was updated on November 12,
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`2015, after the ‘302 patent’s effective filing date. Mot. at 9. As discussed above,
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`11
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`Exhibit 1033 is highly relevant for the proposition that a POSITA would have
`
`recognized in 2015 (and even so today) that CPIs are unpredictable and may only
`
`be effective with respect to a subset of cancers. See Pet. at 28-29; see also Yeda
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`Research, 906 F.3d at 1041.
`
`J.
`
`Exhibit 1057 (Weber)
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`PO’s motion to exclude Exhibit 1057 under FRE 401/402 should be denied
`
`as it is solely based on an allegation that Exhibit 1057 was published in August
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`2015, approximately two months after the ‘302 patent’s priority filing date. Mot.
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`at 13. Even if Exhibit 1057 is not “prior art” as suggested by PO, it remains
`
`admissible as providing support for the expert’s conclusions regarding the known
`
`properties of Bifidobacterium. Significantly, the article expressly states that it
`
`summarized data published no later than March 2015 (“literature review up to
`
`March 2015”). Accordingly, it is relevant and appropriate for Petitioner’s expert to
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`demonstrate the state of the art as of the priority filing date of the ‘302 patent.
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`K. Exhibit 1023 (Targeted Cancer Therapies)
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`The Petition identified Exhibit 1023 as a fact sheet entitled “Targeted
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`Cancer Therapies” from the National Cancer Institute, but identified neither a
`
`publication date nor suggested that Exhibit 1023 was available prior to the filing
`
`date of the ‘302 patent. In any event, Petitioner submits that Exhibit 1023 should
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`not be excluded under FRE 901 as authentication is a “low bar.” Fox Factory, Inc.
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`12
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`v. SRAM, LLC, IPR2016-01876, Paper 59, 63 (Apr. 2, 2018); see also Ericsson Inc.
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`v. Intellectual Ventures I, LLC, IPR2014-01149, Paper 68 at 12 (Dec. 9, 2015)
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`(“The burden of proof for authentication is ‘slight.’”). Where FRE 901 requires a
`
`proponent to “produce evidence sufficient to support a finding that the item is what
`
`the proponent claims it is,” indicia on Exhibit 1023 itself is sufficient to
`
`demonstrate that the document is what Petitioner claims it to be: an undated
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`printout from the National Cancer Institute’s website.
`
`PO’s also objects to Exhibit 1023 under FRE 401/402 because the webpage,
`
`when accessed by PO, was indicated as being updated after the filing date of the
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`‘302 patent. Though not “prior art” for purposes of this proceeding, Exhibit 1023
`
`nonetheless provides general background regarding a class of cancer treatments
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`known as “targeted therapeutics,” which is among many of various types of known
`
`cancer therapies for treating some of the many different types of cancer. Ex. 1002
`
`at ¶98; see also id. at ¶¶93-105. As discussed above, the Board may rely on such
`
`non-prior art as evidence of the background understanding of skilled artisans. See
`
`Yeda Research, 906 F.3d at 1041; Ariosa Diagnostics v. Verinata Health, Inc., 805
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`F.3d 1359, 1365 (Fed. Cir. 2015); Celltrion, Inc. v. Genentech, Inc., IPR2017-
`
`01374, Paper 85 at 52 (Nov. 29, 2018). Finally, policy considerations also weigh
`
`against resorting to formal exclusion. See e.g., Nichia Corp., IPR2012-00005,
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`Paper 68 at 59; S.E.C. v. Guenthner, 395 F. Supp. 2d at 842 n.3.
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`13
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`L.
`
`Exhibit 1059 (Schultz Declaration)
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`PO moves to exclude Exhibit 1059 as being uncited in Petitioner’s Reply. In
`
`the interest of public policy and in light of the Board’s ability to assign appropriate
`
`weight to Exhibit 1059, Petitioner submits that PO’s motion to exclude Exhibit
`
`1059 should be denied. See e.g., Nichia Corp., IPR2012-00005, Paper 68 at 59;
`
`S.E.C. v. Guenthner, 395 F. S