Trials@uspto.gov
`571.272.7822
`
` Paper No. 8
` Entered: April 15, 2019
`
`
`
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`____________
`
`GENOME & COMPANY,
`Petitioner,
`
`v.
`
`THE UNIVERSITY OF CHIGAGO,
`Patent Owner.
`____________
`
`Case No. PGR2019-00002
`Patent 9,855,302 B2
`____________
`
`
`DECISION
`Institution of Post-Grant Review
`35 U.S.C. § 324(a)
`
`
`Before SUSAN L. C. MITCHELL, JACQUELINE T. HARLOW,
`and JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`SCHNEIDER, Administrative Patent Judge.
`
`
`
`
`
`
`
`571.272.7822
`
` Paper No. 8
` Entered: April 15, 2019
`
`
`
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`____________
`
`GENOME & COMPANY,
`Petitioner,
`
`v.
`
`THE UNIVERSITY OF CHIGAGO,
`Patent Owner.
`____________
`
`Case No. PGR2019-00002
`Patent 9,855,302 B2
`____________
`
`
`DECISION
`Institution of Post-Grant Review
`35 U.S.C. § 324(a)
`
`
`Before SUSAN L. C. MITCHELL, JACQUELINE T. HARLOW,
`and JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`SCHNEIDER, Administrative Patent Judge.
`
`
`
`
`
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`INTRODUCTION
`
`I.
`A. Background
`Genome & Company (“Petitioner”) filed a Petition requesting post-
`grant review of claims 1–29 of U.S. Patent No. 9,855,302 B2 (Ex. 1001 “the
`’302 patent”). Paper 1, (“Pet.”). The University of Chicago (“Patent
`Owner”) filed a Preliminary Response. Paper 6 (“Prelim. Resp.”).
`We have authority to determine whether to institute post grant review
`under 35 U.S.C. § 324, which provides that a post grant review may not be
`instituted unless the information presented in the Petition, if unrebutted,
`“would demonstrate that it is more likely than not that at least 1 of the claims
`challenged in the petition is unpatentable.” 35 U.S.C. § 324(a). On April
`24, 2018, the Supreme Court held that a decision to institute may not
`institute review on fewer than all claims challenged in the petition. SAS
`Inst., Inc. v. Iancu, 138 S. Ct. 1348, 1355–56 (2018). Also, in accordance
`with USPTO Guidance, “if the PTAB institutes a trial, the PTAB will
`institute on all challenges raised in the petition.” See Guidance on the
`Impact of SAS on AIA Trial Proceedings (April 26, 2018) (available at
`https://www.uspto.gov/patents-application-process/patent-trial-and-
`appealboard/trials/guidance-impact-sas-aia-trial).
`Having considered the arguments and the evidence presented, for the
`reasons described below, we determine that Petitioner has demonstrated that
`it is more likely than not that at least one of the claims challenged in the
`Petition is unpatentable. Accordingly, we institute a post-grant review of all
`claims and all grounds asserted in the Petition.
`B. Additional Proceedings
`Petitioner represents that there are no related matters. Pet. 3.
`
`2
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`C. Eligibility for Post Grant Review
`Post-grant review is available only for patents “described in section
`3(n)(1)” of the Leahy-Smith America Invents Act (“AIA”), Pub L. No. 112-
`29, 125 Stat. 284 (2011). AIA § 6(f)(2)(A). Those are patents that issue
`from applications “that contain[] or contained at any time . . . a claim to a
`claimed invention that has an effective filing date in section 100(i) of title
`35, United States Code, that is on or after” “the expiration of the 18-month
`period beginning on the date of the enactment of” the AIA. See AIA
`§ 3(n)(1).
`Because the AIA was enacted on September 16, 2011, post-grant
`review is available only for patents that, at one point, contained at least one
`claim with an effective filing date, as defined by 35 U.S.C. § 100(i), on or
`after March 16, 2013. The earliest filing date for the ’302 patent is June 1,
`2015, which is after the March 16, 2013 date. See Ex. 1001 [60].
`The AIA also requires that the petition be filed within nine months of
`the issue date of the patent being challenged. 35 U.S.C. § 321(c). The ’302
`patent issued on January 2, 2018. Ex. 1001 [45]. The Petition has been
`accorded a filing date of October 2, 2018, within the nine-month window.
`Based on the foregoing, we conclude that the ’302 patent is eligible
`for post-grant review and that Petitioner has timely filed its petition.
`D. The ’302 Patent (Ex. 1001)
`The ’302 patent, titled “Treatment of Cancer by Manipulation of
`Commensal Microflora” issued on January 2, 2018, from U.S. Patent
`Application No. 15/170,284 filed on June 1, 2016. Ex. 1001, [54], [45],
`[21], [22]. . The ’752 patent claims priority to U.S. Provisional Application
`No. 60/169,112 filed on June 1, 2015, and U.S. Provisional Application No.
`60/248,741 filed on October 30, 2015. Id. at [60].
`
`3
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`The ’302 patent teaches the treatment or prevention of cancer through
`the use of commensal microflora either alone or in combination with one or
`more co-treatments. Ex. 1001, Abstract.
`The ’302 patent discloses that the co-treatment can be the
`administration of an immune checkpoint inhibitor (“CPI”).1 Ex. 1001, col.
`5, ll. 7–8. The CPI used in the practice of the invention disclosed in the ’302
`patent can be a protein of a peptide, an antibody or fragment thereof, or an
`interfering nucleic acid molecule. Id. at col. 5, ll. 7–20
`The ’302 patent discloses that one of the microflora that can be used
`in practice of the disclosed invention is bacteria of the genus
`Bifidobacterium. Ex. 1001, col. 3, ll. 10–29.
`E. Illustrative Claims
`Of the challenged claims, claims 1 is the sole independent claim and
`reads as follows:
`1. A method of treating cancer in a human subject comprising
`co-administering to the subject an immune checkpoint
`inhibitor and a bacterial formulation comprising bacteria of
`the genus Bifidobacterium.
`Ex. 1001, col. 41, ll. 61–64.
`F. The Asserted Grounds of Unpatentability
`
`
`1Immune checkpoint inhibitors are described as follows: “We have learned
`over the last decade that powerful immunologic effector cells may be
`blocked by inhibitory regulatory pathways controlled by specific molecules
`often called ‘immune checkpoints.’ These checkpoints serve to control or
`turn off the immune response when it is no longer needed to prevent tissue
`injury and autoimmunity.” Ex. 1016, Abstract. Drugs that inhibit these
`pathways are called checkpoint inhibitors and their use is seen as a potential
`new strategy for treating cancer. Id.
`
`
`4
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`Petitioner contends that the challenged claims are unpatentable on the
`following grounds. Pet. 7.
`Ground References
`
`Basis
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`7
`
`8
`
`
`
`Korman2, Singh,3 and
`Dong4
`Korman, Singh, Dong, and
`van der Waaij5
`Korman, Singh, Dong, and
`Topalian6
`Korman and Kohwi7
`
`§ 112(a) Lack
`of Enablement
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`Korman, Kohwi, and Singh § 103(a)
`Korman, Kohwi, and van
`§ 103(a)
`der Waaij
`Korman, Kohwi, and
`Topalian
`
`§ 103(a)
`
`Claims
`Challenged
`1–29
`
`1–9, 12–17, 19–
`25, 27, and 28
`10, 11, and 26
`
`18 and 29
`
`1–4, 7–9, 12–17,
`19–25, 27, and
`28
`5, 6, 23, and 24
`10, 11, and 26
`
`18 and 29
`
`
`2 Korman et al., US 2009/0217401 A1, published Aug. 27, 2009 (“Korman”)
`Ex. 1003.
`3 Singh et al., Bifidobacterium longum, a lactic acid-producing intestinal
`bacterium inhibits colon cancer and modulates intermediate biomarkers of
`cancer carcinogenesis, 18 CARCINOGENESIS 833 (1997) (“Singh”) Ex. 1004.
`4 Dong et al., The role of intestinal bifidobacteria on immune system
`development in young rats, 86 EARLY HUMAN DEVEL. 51 (2010) (“Dong”)
`Ex. 1005.
`5 van der Waaij et al., The influence of antibiotics on gut colonization, 18 J.
`ANTIMICROBIAL CHEMOTHERAPY 155 (1986) (“van der Waaij”) Ex. 1010.
`6 Topalian et al., Survival, Durable Tumor Remission, and Long-Term Safety
`in Patients with Advanced Melanoma Receiving Nivolumab, 32 J. CLINICAL
`ONCOL. 1020 (2014) (“Topalian”) Ex. 1006.
`7 Kohwi et al., Antitumor Effects of Bifidobacterium infantis in Mice,
`69 GANN. 613 (1978) (“Kohwi”) Ex. 1007.
`
`5
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`Ground References
`
`Basis
`
`Claims
`Challenged
`1–9, 12–17, 19–
`25, 27, and 28
`10, 11, and 26
`
`§ 103(a)
`
`§ 103(a)
`
`9
`
`10
`
`11
`
`Korman, Mohania,8 and
`Prakash9
`Korman, Mohania,
`Prakash, and van der Waaij
`Korman, Mohania,
`Prakash, and Topalian
`Petitioner also relies on the Declaration of Jonathan Braun, M.D.,
`Ph.D. (Ex. 1002).
`
`§ 103(a)
`
`18 and 29
`
`II. ANALYSIS
`A. Claim Construction
`In a post-grant review filed before November 13, 2018, the Board
`interprets claim terms in an unexpired patent according to the broadest
`reasonable construction in light of the specification of the patent in which
`they appear. 37 C.F.R. § 100(b) (2018);10 Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131, 2142 (2016) (affirming applicability of broadest reasonable
`construction standard to trial proceeding before the USPTO.). Under that
`standard, and absent any special definitions, we generally give claim terms
`
`
`8 Mohania et al., Modulation of expression of Programmed Death-1 by
`administration of probiotic Dahi in DMH-induced colorectal carcinogenesis
`in rats, 84 ACTA BIOMED. 102 (2013) (“Mohania”) Ex. 1008.
`9 Prakash et al., US 2010/028449 A1, published Feb. 4, 2010 (“Prakash”)
`Ex. 1009.
`10 The Office recently changed the claim construction standard to be
`employed in a post-grant review for petitions filed on or after November 13,
`2018. See Changes to the Claim Construction Standard for Interpreting
`Claims in Trial Proceedings Before the Patent Trial and Appeal Board, 83
`Fed. Reg. 51,340 (October 11, 2018). However, based on the filing date of
`the Petition in this proceeding, the applicable claim construction standard
`remains as set forth in 37 C.F.R. § 42.100(b) (2016).
`
`6
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`their ordinary and customary meaning, as would be understood by one of
`ordinary skill in the art at the time of the invention. See In re Translogic
`Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any special definitions
`for claim terms must be set forth with reasonable clarity, deliberateness, and
`precision. See In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`We determine that it is unnecessary to expressly construe any claim
`terms for purposes of this Decision. See Wellman, Inc. v. Eastman Chem.
`Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only be
`construed ‘to the extent necessary to resolve the controversy.’”) (quoting
`Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir.
`1999)).
`
`B. Level of Ordinary Skill in the Art.
`The level of ordinary skill in the art is a factual determination that
`provides a primary guarantee of objectivity in an obviousness analysis. Al-
`Site Corp. v. VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966); Ryko Mfg. Co. v. Nu-
`Star, Inc., 950 F.2d 714, 718 (Fed. Cir. 1991)).
`Dr. Braun, Petitioner’s proffered expert, defines a person of ordinary
`skill in the art as having an advanced degree or its substantial equivalent in
`the biological sciences, including specifically in the fields of immunology,
`microbiology and the microbiome, and oncology, coupled with research
`experience in those fields. Ex. 1002 ¶ 40. At this stage of the proceeding,
`and without opposition from Patent Owner at this time, we determine that
`Petitioner’s description of the level of ordinary skill in the art is supported
`by the current record. Id. For purposes of this Decision, therefore, we adopt
`Petitioner’s description.
`
`7
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`We also note that the applied prior art reflects the appropriate level of
`skill at the time of the claimed invention. See Okajima v. Bourdeau,
`261 F.3d 1350, 1355 (Fed. Cir. 2001).
`C. Ground 1 – Enablement.
`Petitioner asserts that claims 1–29 are unpatentable for failure to
`comply with the enablement requirement set forth in 35 U.S.C. §112(a).
`“Section 112 requires that the patent specification enable those skilled
`in the art to make and use the full scope of the claimed invention without
`undue experimentation. . . . [S]ee also In re Goodman, 11 F.3d 1046, 1050
`(Fed. Cir. 1993) (‘[T]he specification must teach those of skill in the art how
`to make and how to use the invention as broadly as it is claimed.’).”
`Invitrogen Corp. v. Clontech Labs. Inc., 429 F.3d 1052, 1070–71 (Fed. Cir.
`2005) (internal quotes omitted).
`Some experimentation, even a considerable amount, is not “undue” if,
`e.g., it is merely routine, or if the specification provides a reasonable amount
`of guidance as to the direction in which the experimentation should proceed.
`In re Wands, 858 F.2d 731, 736–37 (Fed. Cir. 1988). “Factors to be
`considered in determining whether a disclosure would require undue
`experimentation . . . include (1) the quantity of experimentation necessary,
`(2) the amount of direction or guidance presented, (3) the presence or
`absence of working examples, (4) the nature of the invention, (5) the state of
`the prior art, (6) the relative skill of those in the art, (7) the predictability or
`unpredictability of the art, and (8) the breadth of the claims.” Id. at 737.
`“Whether undue experimentation is needed is not a single, simple factual
`determination, but rather is a conclusion reached by weighing many factual
`considerations.” Id.
`1. Petitioner’s Position
`
`8
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`Petitioner contends that the specification of the ’302 patent fails to
`adequately enable one skilled in the art to make and use the disclosed
`invention for the full scope of the claims. Pet. 36. Petitioner argues that
`when the Wands factors are properly considered, the factors lead to the
`conclusion that undue experimentation would be required to practice the full
`scope of the claims. Id.
`a. The Nature of the Invention
`Petitioner begins by addressing the nature of the invention. Petitioner
`points out that the invention is directed to treating cancer in a human subject
`by administering both a CPI and a bacterial formulation comprising
`Bifidobacterium. Pet. 36. Petitioner contends that the claims are not limited
`to a specific form of cancer nor to a specific species of Bifidobacterium. Id.
`Petitioner also points out that the broader claims do not specify the CPI to be
`used. Id.
`Petitioner relies on the Declaration of Dr. Braun to support these
`contentions. Id. (citing Ex. 1002 ¶¶ 129–31). In the paragraphs cited in the
`Petition, Dr. Braun cites to earlier portions of the declaration where he
`discusses the teachings of theׄ ’302 patent. Ex. 1002 ¶ 131 (citing to ¶¶ 59–
`63). Dr. Braun discusses the examples in the ’302 patent and explains how
`the teachings of the examples are very limited. Ex. 1002 ¶¶ 59–63.
`b. Level of Ordinary Skill in the Art
`Petitioner argues that the level is skill in the art is high, an assessment
`with which we agree on this record. Pet. 37; see supra Section II.B.
`Petitioner contends that the ordinarily skilled artisan would have a
`specialized knowledge of cancer, immunology, and microbiota. Petitioner
`contends that this specialized training is necessary as developing a cancer
`therapeutic is difficult, complicated, and highly unpredictable. Id.
`
`9
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`In support of these contentions, Petitioner points to the Declaration of
`Dr. Braun. Id.; Ex. 1002 ¶¶ 132 and 133. In his Declaration, Dr. Braun cites
`to earlier paragraphs in his declaration where he discusses in detail the
`support for his opinion as to the level of skill required to develop a cancer
`therapeutic. Id. ¶ 133 (citing ¶¶ 93–109).
`c. The Breadth of the Claims
`Petitioner contends that the claims are very broad in that they cover
`“thousands of different combinations of cancers, immune checkpoint
`inhibitors and genera of Bifidobacterium.” Pet. 38. Petitioner contends that
`the claims are directed to any type of cancer and that the specification of the
`’302 patent lists more than 165 types of cancer that can be treated. Id.
`Petitioner also contends that the broader claims do not specify the CPI that is
`to be used and that CPIs include a broad class of agents such as proteins,
`including antibodies and fragments thereof, and nucleic acids. Id.
`In support of these contentions, Petitioner cites to the Declaration of
`Dr. Braun. Id. at 38–41 citing Ex. 1002 ¶¶ 136–146. In the cited
`paragraphs, Dr. Braun cites to an earlier discussion in his declaration where
`he describes in detail different types of cancer and explains how each is
`treated by different methods. Ex. 1002 ¶ 138 (citing ¶¶ 95–96). In this
`earlier discussion, Dr. Braun cites to additional references that support his
`opinions. See, e.g. Ex. 1002 ¶ 95 (citing to Kandoth11); Ex. 1021.
`Dr. Braun also discusses the different types of CPIs and how they
`have been effective in treating a limited number of cancers and only for a
`limited subset of patients affected by those cancers. Ex. 1002 ¶¶ 100–103.
`
`
`11 Kandoth, et al., Mutational landscape and significance across 12 major
`cancer types, 502 NATURE 333 (2013) (“Kandoth”) Ex. 1021.
`
`10
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`In support of his opinions, Dr. Braun cites to Pardoll,12 which discusses CPIs
`and their use in treating cancer. Id.
`d. Presence of Working Examples
`Petitioner contends that the examples in the ’302 patent are limited to
`two specific types of cancer, melanoma and bladder, and one CPI. Pet. 41.
`With respect to the Bifidobacterium used in the examples, Petitioner
`contends that the ’302 patent only used mouse feces, which contains one
`species of Bifidobacterium and other gut bacteria and another composition
`comprising a mixture of four different species of Bifidobacterium. Id. at 41–
`42. Petitioner also notes that the data presented in the ’302 patent are
`limited to mouse data and that no human data are presented. Id. at 42.
`In support of these contentions, Petitioner relies on the Declaration of
`Dr. Braun. Id. As noted above, Dr. Braun discusses the limited nature of
`the experiments reported in the examples citing various passages in the ’302
`patent. Ex. 1002 ¶¶ 59–63 and 147–149.
`e. Amount of Guidance in the Specification
`Petitioner contends that the ’302 patent provides no guidance as to
`which CPI to select to treat a specific cancer. Pet. 42. Petitioner contends
`that that only guidance in in the examples is limited to two types of cancer
`and one CPI. Id. Petitioner contends that given the scope of the claims and
`the unpredictable nature of the technology, the guidance given in the ’302
`patent is inadequate. Id. at 43.
`Petitioner relies on the Declaration of Dr. Braun to support these
`contentions. Id. As discussed above, Dr. Braun discusses the examples
`
`
`12 D. Pardoll, The blockade of immune checkpoints in cancer immunotherapy,
`12 NAT. REV. CANCER 252 (2012) (“Pardoll”) Ex. 1026.
`
`11
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`provided in the ’302 patent and the guidance given in the rest of the
`specification. Ex. 1002 ¶¶ 41–63, 150–151.
`f. Predictability of the Art.
`Petitioner contends that the art relating to the claimed invention is
`highly unpredictable. Pet. 43. Petitioner lists several different factors in
`support of this contention, including:
`- Cancer is a term that embraces a variety of specific diseases
`with different etiologies, outcomes and therapies;
`- There are a limited number of CPIs that have been shown to
`work for a limited number of cancers, and for only a limited
`subset of patients with those cancers;
`- The properties of Bifidobacterium are species and sometimes
`strain specific; and
`- Only certain species of Bifidobacterium have been shown to
`be effective against cancer.
`
`Pet. 43.
`Petitioner contends that cancer therapy is an unpredictable art.
`Pet. 44. Petition contends that cancers develop in different ways and can
`require different methods of treatment. Id.
`In support of these contentions, Petitioner cites to the Declaration of
`Dr. Braun. Id. Dr. Braun provides a detailed analysis supporting his
`conclusion that the art of treating cancer is unpredictable. Ex. 1002 ¶¶ 93–
`109 and 152–155. In support of his conclusions, Dr. Braun cites to Kandoth
`and Kumar13 for the proposition that there are a variety of different cancer
`
`
`13 Kumar et al., Drug Target for Cancer Treatment: An Overview, 5 MED.
`CHEM. 115 (2015) (“Kumar”) Ex. 1022.
`
`12
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`types and different methods for treating cancers. Ex. 1002 ¶¶ 95–97.
`Dr. Braun cites to Pardoll to support his conclusions regarding the limited
`effectiveness of CPIs, and cites to DiMasi14 for the proposition that
`development of a cancer therapy is difficult and complicated. Id. at ¶¶ 100–
`104.
`
`g. Amount of Experimentation
`Petitioner contends that it would require an undue amount of
`experimentation to practice the full scope of the claims of the ’302 patent.
`Pet. 45. Petitioner argues that it would require more than 100,000
`experiments to test all the disclosed CPIs with all the disclosed species of
`Bifidobacterium to test their effectiveness against the range of cancers
`recited in the ’302 patent. Id. at 46. Petitioner contends that the number of
`experiments required is actually even greater as the patent does not give any
`specific guidance as to the routes of administration. Petitioner contends that
`the sheer volume or experiments required coupled with the limited guidance
`in the ’302 patent compels the conclusion that undue experimentation is
`require to practice the full scope of the invention. Id. at 48.
`Petitioner supports these contentions with the Declaration of
`Dr. Braun. Id. citing Ex. 1002 ¶¶ 156–165. Dr. Braun bases his opinion that
`undue experimentation would be required on his analysis of the ’302 patent.
`Ex. 1002 ¶¶ 156–165.
`2. Patent Owner’s position
`Patent Owner contends that Petitioner has not sufficiently established,
`for purposes of institution, that the challenged claims are non-enabled.
`
`
`14 DiMasi and Grabowski, Economic of New Oncology Drug Development,
`25 J. CLINICAL ONCOL. 209 (2007) (“DiMasi”) Ex. 1027.
`
`13
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`Prelim. Resp. 2. According to Patent Owner, Petitioner’s non-enablement
`argument “is deficient because it concludes, based solely on the quantity,
`that the allegedly required testing would have been undue.” Id. at 3. Patent
`Owner contends that Petitioner has offered no other evidence to support the
`conclusion that the undue experimentation would be required. Id. Patent
`Owner also contends that even if a large number of experiments were
`required, that alone is not enough; Petitioner must also show that the
`experiments are not of a routine nature. Id. at 3–6. Patent Owner contends
`that Petitioner has not made such a showing. Id.
`3. Discussion
`We have considered the arguments advanced by the parties and
`conclude that, for purposes of this Decision, Petitioner has established that it
`is more likely than not that it will prevail in establishing that the claims are
`not enabled. Petitioner’s Wands analysis establishes that the claims
`challenged under ground 1 are extremely broad in that they do not limit the
`type of cancer treated nor do they specify the genera of Bifidobacterium that
`can be used. Ex. 1002 ¶ 130. The broader claims are not limited as to the
`nature of the CPI that can be used. Id. The evidence of record shows that
`different cancers respond to different treatments differently. Ex. 1002 ¶ 96;
`Ex. 1022, 115–123. The record also shows that CPIs are numerous and
`varied. Ex. 1002 ¶¶ 100–103. There is evidence of record that developing a
`cancer treatment is difficult and complicated. Ex. 1002 ¶ 104; Ex. 1027,
`206.
`
`The working examples are markedly limited. The examples only
`address two types of cancer using only one CPI and 4 species of
`Bifidobacterium. Ex. 1001, col. 36, l. 56–col. 37, l. 10. In addition, the
`Specification gives no guidance as to how to select CPIs and
`
`14
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`Bifidobacterium that will work in the claimed method without resorting to
`trial and error. Instead the Specification lists 36 different species of
`Bifidobacterium, id. at col. 3, ll. 10–29, and gives a broad definition of a
`CPI, id. at col. 5, ll. 8–11. Based on the record before us, we find that each
`of the Wands factors recited above weighs in favor of Petitioner’s contention
`that the claims are not enabled for the full scope of the claims.
`Patent Owner contends that Petitioner’s Wands analysis is deficient in
`that it only relies on the quantity of experiments that are needed and does not
`address whether those experiments would have been routine or whether the
`Specification provides a reasonable amount of guidance. Prelim. Resp. 2–4.
`We are unpersuaded by Patent Owner’s argument. As discussed above,
`Petitioner has demonstrated that the amount of guidance in the Specification
`is minimal. Pet. 42–43. In addition, Dr. Braun’s conclusion that extensive
`and undue experimentation would be required in based not only on the
`number of experiments involved (which purportedly could exceed 100,000)
`but on additional factors such as the unpredictability of cancer treatments
`and the unpredictable nature of CPIs. Ex. 1002 ¶ 166. On the record before
`us, it appears that the Specification does not enable the full scope of the
`claims. Considering all of the Wands factors, we find that Petitioner is likely
`to prevail in showing the unpatentability of at least one claim of the ’302
`patent.
`
`D. Grounds 2–4 Obviousness based on Combinations
`Including Korman, Singh, and Dong
`Petitioner contends that claims 1–9, 12–17, 19–25, 27, and 28 would
`have been rendered obvious by the teachings of Korman combined with
`Singh and Dong. Pet. 50–57. Petitioner also alleges that claims 10, 11, and
`26 are rendered obvious by the teachings of Korman, Singh, Dong and van
`
`15
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`der Waaij. Pet. 57–58. Petitioner contends that claims 18 and 29 are
`rendered obvious over Korman, Singh, Dong and Topalian. Pet. 58–59. As
`discussed more fully below, on the record before us we find that Petitioner
`has not demonstrated that it more likely than not that at least one claim
`would have been obvious over the references in these grounds asserted by
`Petitioner.
`Patent Owner addresses these three grounds together, and contends
`that one skilled in the art would not have been motivated to combine the
`teachings of Korman, Singh, and Dong. Prelim Resp. 6–12. Patent Owner
`contends that one skilled in the art would not have been motivated to
`combine the teachings of the references as the art teaches that the CPI of
`Korman is immunostimulatory and the Bifidobacterium of Singh and Dong
`are immunosuppressive. Prelim. Resp. 6.15 Patent Owner contends that
`“combining an immunosuppressive Bifidobacterium with an
`immunostimulatory checkpoint inhibitor would have been antithetical to one
`of ordinary skill.” Id. Patent Owner points out that the Examiner found a
`similar argument persuasive in allowing the present claims over similar prior
`art. Id.
`We will address these three grounds together. The question of
`obviousness is resolved on the basis of underlying factual determinations
`
`15 Patent Owner asserts that during prosecution, it overcame an obviousness
`rejection by arguing that the Bifidobacterium species taught by that art is
`immunosuppressive “and that combining an immunosuppressive
`Bifidobacterium with an immunostimulatory checkpoint inhibitor would
`have been antithetical to one of ordinary skill.” Prelim. Resp. 6. Petitioner
`does not appear to dispute Patent Owner’s contention that an ordinarily
`skilled artisan would have avoided co-administration of an
`immunosuppressive Bifidobacterium species with an immunostimulatory
`CPI. See Pet. 2, note 1, 13–16.
`
`16
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`including (1) the scope and content of the prior art, (2) any differences
`between the claimed subject matter and the prior art, (3) the level of skill in
`the art, and (4) where in evidence, so-called secondary considerations.
`Graham, 383 U.S. at 17–18. If the differences between the claimed subject
`matter and the prior art are such that the subject matter, as a whole, would
`have been obvious at the time the invention was made to a person having
`ordinary skill in the art to which said subject matter pertains, the claim is
`unpatentable under 35 U.S.C. § 103(a). KSR Int’l Co. v. Teleflex Inc., 550
`U.S. 398, 406 (2007).
`An invention
`composed of several elements is not proved obvious
`merely by demonstrating that each of its elements was,
`independently, known in the prior art. Although common sense
`directs one to look with care at a patent application that claims
`as innovation the combination of two known devices according
`to their established functions, it can be important to identify a
`reason that would have prompted a person of ordinary skill in
`the relevant field to combine the elements in the way the
`claimed new invention does.
`
`
`KSR, 550 U.S. at 418.
`
`
`1. Korman
`Korman relates to the use of human monoclonal antibodies to treat
`cancer. Ex. 1003 Abstract. Korman teaches the use of anti-PD-1 antibodies
`and anti-CTLA-4 antibodies to treat cancer. Id. Korman teaches that the
`antibodies act as CPIs as they bind to the respective proteins thereby
`enhancing the immune response to cancer cells. Ex. 1003 ¶¶ 498 and 501.
`Korman teaches that the antibodies can be effective against colorectal cancer
`cells and SA1/N fibrosarcoma cells. Id.
`2. Singh
`
`17
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`Singh reports a study to determine the effectiveness of
`Bifidobacterium longum to treat cancer. Ex. 1004, 1 Abstract. Singh
`teaches that oral administration of Bifidobacterium longum exerts strong
`antitumor activity. Id. Singh teaches that daily oral administration of
`lyophilized cultures of B. longum resulted in “significant suppression of
`colon cancer incidence, tumor multiplicity and reduced tumor volume.” Id.
`3. Dong
`Dong reports a study on the effect of intestinal bifidobacteria on the
`development of immunity during development. Ex. 1005 Abstract. Dong
`teaches that administration of bifidobacteria “promoted dendritic cell
`maturation in Peyer's Patches, up-regulated IL-12, IL-10, interferon-γ
`mRNA and the interferon-γ/IL-4 ratio in intestinal mucosa, increased
`interferon-γ gene expression in cultured PBMCs, and raised
`immunoglobulin-M secretion in cultured PBMCs.” Id. Dong teaches
`intestinal bifidobacteria can affect “the development of both gut and
`systemic immunity in early life.” Id.
`4. Analysis
`Petitioner contends that Korman teaches a method for treating cancer
`in humans by administering CPIs such as anti-PD-1 and anti-CTLA-4
`antibodies that bind to their respective immune checkpoint proteins. Pet. 50.
`In support of this position, Dr. Braun testifies that “Korman ‘401 showed
`that that intraperitoneal injection of anti PD-1 and anti CTLA-4 antibodies
`both alone and in combination reduced tumor growth in MC38 colorectal
`cancer cells and SA1/N fibrosarcoma cells.” Ex. 1002 ¶ 168.
`Petitioner contends that Singh teaches that oral administration of
`Bifidobacterium longum exerts strong antitumor activity. Pet. 50. In
`support of this position, Petitioner’s expert testifies that “Singh showed that
`
`18
`
`
`
`PGR2019-00002
`Patent 9,855,302 B2
`
`
`daily oral administration of “[l]yophilized cultures of B. longum …
`equivalent to 4 x 1010 live cells/g diet” (Id at p. 2, 2nd col.) resulted in
`‘significant suppression of colon tumor incidence, tumor multiplicity, and
`reduced tumor volume.’” Ex. 1002 ¶ 169 (quoting Ex. 1004 Abstract).
`Petitioner contends that Dong teaches that Bifidobacterium longum is
`immunostimulatory. Pet. 50. In support of this position, Dr. Braun testifies
`that “Dong showed that Bifidobacterium longum induced maturation in
`dendritic cells characterized by increased expression of CD86, IL-12, and
`IFN-γ, and that such induced maturation of dendritic cells would favor a T-
`helper cell response of the body in a Th1 type.” Ex. 1002 ¶ 170.
`Petitioner contends that it would have been obvious to one skilled in
`the art to combine the teachings of Korman and Singh t
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
