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`Trials@uspto.gov
`571-272-7822
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` Paper No. 12
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` Entered: May 30, 2019
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FOUNDATION MEDICINE, INC.,
`Petitioner,
`
`v.
`
`CARIS MPI, INC.,
`Patent Owner.
`____________
`
`Case IPR2019-00170
`Patent 9,372,193 B2
`____________
`
`
`
`Before CHRISTOPHER G. PAULRAJ, JACQUELINE T. HARLOW and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`HARLOW, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`35 U.S.C. § 314
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`I. INTRODUCTION
`Foundation Medicine, Inc. (“Petitioner”) filed a Petition (Paper 3,
`“Pet.”), requesting institution of an inter partes review of claims 1–14 of
`U.S. Patent No. 9,372,193 B2 (Ex. 1001, “the ’193 patent”). Caris MPI, Inc.
`(“Patent Owner”) timely filed a Preliminary Response (Paper 7, “Prelim.
`Resp.”). Pursuant to our authorization (Paper 8), Petitioner filed a Reply to
`Patent Owner’s Response (Paper 9, “Reply”) and Patent Owner filed a Sur-
`Reply to Petitioner’s Reply (Paper 10, “Sur-Reply”).
`Under 35 U.S.C. § 314(a), an inter partes review may not be instituted
`unless the information presented in the petition “shows that there is a
`reasonable likelihood that the petitioner would prevail with respect to at
`least 1 of the claims challenged in the petition.” For the reasons stated
`below, we determine that there is a reasonable likelihood that Petitioner
`would prevail with respect to at least one challenged claim. We hereby
`institute inter partes review of the challenged claims on all the grounds of
`unpatentability asserted in the Petition.
`A. Related Matters
`The ’193 patent is the subject of a co-pending district court
`proceeding, Caris MPI, Inc. v. Foundation Medicine, Inc., Civil Action
`No: 1:17-cv-12194-MLW (D. Mass.). Pet. 2; Paper 4, 2. In addition,
`Petitioner has filed petitions seeking inter partes review of several other
`patents held by Patent Owner, including: IPR2019-00164 (U.S. Patent No.
`8,880,350 B2), IPR2019-00165 (U.S. Patent No. 9,092,392 B2), IPR2019-
`00166 (U.S. Patent No. 9,292,660 B2), IPR2019-00171 (U.S. Patent No.
`9,383,365 B2), and IPR2019-00203 (U.S. Patent No. 9,292,660 B2). We
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`instituted inter partes reviews in IPR2019-00166 and IPR2019-00203 on
`May 14, 2019. See IPR2019-00166 (Paper 12); IPR2019-00203 (Paper 12).
`B. The ’193 Patent
`The ’193 patent, titled “System and Method for Determining
`Individualized Medical Intervention for a Disease State,” issued on June 21,
`2016. Ex. 1001, (54), (45). The ’193 patent relates to a “system and method
`for determining individualized medical intervention for a particular disease
`state,” such as cancer, that “includes the molecular profiling of a biological
`sample from the patient.” Id. at Abstract.
`According to the ’193 patent, “[a]lthough the molecular mechanisms
`behind various disease states have been the subject of studies for years, the
`specific application of a diseased individual’s molecular profile in
`determining treatment regimens and therapies . . . has been disease specific
`and not widely pursued.” Id. at 1:45–48. The patent states that this
`approach “presents a risk that an effective treatment regimen may be
`overlooked for a particular individual” because some treatment regimens
`traditionally administered for one particular disease state also may be
`effective in treating a different disease state. Id. at 1:58–65. Thus, the
`’193 patent states, “there is a need for a system and method for determining
`an individualized medical intervention” for a patient that can identify
`“additional targets” or “molecular mechanisms, genes, gene expressed
`proteins, and/or combinations of such.” Id. at 2:19–25, 2:30–35. The
`’193 patent states that this approach would provide patients “with a viable
`therapeutic alternative to those treatment regimens which currently exist.”
`Id. at 2:25–29.
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`Figure 2 of the ’193 patent, reproduced below, provides an overview
`of an exemplary method for determining individualized medical intervention
`that utilizes a patient’s molecular profile. Id. at 5:4–7, 13:10–15.
`
`
`In step 52, at least one test is performed for at least one molecular
`target (e.g., one or more genes, proteins, and/or molecular mechanisms)
`from a patient’s biological sample. Id. at 13:19–25. Tests that may be
`performed include immunohistochemistry (IHC) analysis 54, microarray
`analysis 56, and/or any other known molecular tests 58. Id. at 13:25–35.
`The ’193 patent states that IHC analysis may be performed for such proteins
`as “Her2/Neu, ER, PR, c-kit, EGFR, MLH1, MSH2, CD20, p53, Cyclin D1,
`bcl2, COX-2, Androgen receptor, CD52, PDGFR, AR, CD25, and VEGF.”
`Id. at 2:64–3:4. The patent further discloses that microarray analysis may be
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`performed for myriad genes, including AR, EGFR, KIT, MLH1, PTEN, and
`PDGFRA. Id. at 3:5–23.
`In step 60, “a determination is made as to whether one or more of the
`targets that were tested for in step 52 exhibit a change in expression
`compared to a normal reference for that particular target.” Id. at 13:44–47.
`A change in expression may be observed via differential staining, the
`amount of overexpression or underexpression, and/or “by an absence of one
`or more genes, gene expressed proteins, molecular mechanisms, or other
`molecular findings.” Id. at 13:47–66.
`Next, “at least one non-disease specific agent is identified that
`interacts with each target having a changed expression in step 70.” Id. at
`14:1–4. The ’193 patent states that a “non-disease specific agent is a
`therapeutic drug or compound not previously associated with treating the
`patient’s diagnosed disease that is capable of interacting with the target from
`the patient’s biological sample that has exhibited a change in expression.”
`Id. at 14:5–9.
`Finally, in step 80, “a patient profile report may be provided which
`includes the patient’s test results for various targets and any proposed
`therapies based on those results.” Id. at 14:25–27. The ’193 patent discloses
`a computerized system for generating the report, which includes, among
`other things, an application program stored in a memory that is accessible by
`a processor, internal databases, and external databases. Id. at 12:50–58. The
`internal databases can include information about the patient biological
`sample, patient test results from molecular profiling, clinical data, and study
`protocols. Id. at 13:1–5. The external databases can include drug libraries,
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`gene libraries, disease libraries, and public databases such as GenBank. Id.
`at 13:5–9.
`The ’193 patent states that the processor comprises instructions for
`assessing a patient’s molecular profile, determining whether at least one
`molecular target exhibits a change in expression “compared to a normal
`reference,” and accessing a drug therapy database to identify drug therapies.
`Id. at 4:4–24. The patent states that a drug therapy may be identified “from
`an automated review of an extensive literature base and/or an automated
`review of data generated from clinical trials.” Id. at 4:45–49.
`C. Challenged Claims
`Petitioner challenges claims 1–14 of the ’193 patent. Claim 1, the
`sole independent claim of the ’193 patent, is illustrative, and is reproduced
`below:
`A system for generating a report identifying at least one
`1.
`therapeutic agent for an individual with a cancer comprising:
`a.
`at least one device configured to assay a plurality of
`molecular targets in a biological sample to determine molecular
`profile test values for the plurality of molecular targets, wherein
`the plurality of molecular targets comprises AR, EGFR, HER2,
`KIT, MLH1, PTEN, and PDGFRA; and
`b.
`at least one computer database comprising:
`i.
`a reference value for each of the plurality of
`molecular targets; and
`ii.
`a listing of available therapeutic agents for
`each of the plurality of molecular targets;
`c. a computer-readable program code comprising
`instructions to input the molecular profile test values and to
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`compare each of the molecular profile test values with a
`corresponding reference value from the at least one computer
`database in (b)(i);
`d.
`a computer-readable program code comprising
`instructions to access the at least one computer database and to
`identify at least one therapeutic agent from the listing of available
`therapeutic agents for the plurality of molecular targets wherein
`the comparison to the reference values in (c) indicates a likely
`benefit of the at least one therapeutic agent; and
`e.
`a computer-readable program code comprising
`instructions to generate a report that comprises a listing of the
`molecular targets for which the comparison to the reference
`value indicated a likely benefit of the at least one therapeutic
`agent in (d) and the at least one therapeutic agent identified in
`(d).
`
`D. Evidence Relied Upon
`Petitioner relies upon the following references (Pet. 3, 16–22):
`WO 03/017038 A2
`Feb. 27, 2003
`(Ex. 1004)
`Lu
`US 2002/0150966 A1
`Oct. 17, 2002
`(Ex. 1006)
`Muraca
`Illumina® Gene Expression Profiling, Technical Bulletin, RNA Profiling
`with the DASL® Assay (2005) (Ex. 1005, “Illumina”).
`McDoniels-Silvers et al., Differential Expression of Critical Cellular Genes
`in Human Lung Adenocarcinomas and Squamous Cell Carcinomas in
`Comparison to Normal Lung Tissues, 4(2) NEOPLASIA 141–150 (2002)
`(Ex. 1007).
`Petitioner also relies on the Declaration of Paul T. Spellman, Ph.D.
`(Ex. 1002).
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`E. Asserted Grounds of Unpatentability
`Petitioner asserts the following grounds of unpatentability (Pet. 3):
`
`Claims
`1–14
`2, 3
`7, 11
`
`References
`Basis
`§ 103 Lu and Illumina
`§ 103 Lu, Illumina, and Muraca
`§ 103 Lu, Illumina, and McDoniels-Silvers
`
`II. ANALYSIS
`A. Level of Ordinary Skill in the Art
`Petitioner contends that a person of ordinary skill in the art (“skilled
`artisan” or “POSA”) for the ’193 patent “would have had a Ph.D. in
`genetics, molecular biology, bioinformatics, or a related field, and at least
`five years of research experience in an academic or industry setting,
`including at least two to three years of research experience in the field of
`cancer genomics.” Pet. 15–16 (citing Ex. 1002 ¶ 32). Patent Owner does
`not address the requisite level of skill in its Preliminary Response.
`For purposes of this decision, we adopt Petitioner’s presently
`undisputed definition of the level of ordinary skill in the art, as it is
`consistent with the level of skill in the art reflected in the prior art of record.
`See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001).
`B. Claim Construction
`Based on the filing date of the Petition (November 5, 2018), the Board
`interprets claim terms in the ’193 patent according to the broadest reasonable
`construction in light of the specification of the patent in which they appear.
`37 C.F.R. § 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131,
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`2142–46 (2016).1 Under that standard, and absent any special definitions,
`we give claim terms their ordinary and customary meaning, as would be
`understood by one of ordinary skill in the art at the time of the invention. In
`re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
`Additionally, any special definitions for claim terms must be set forth with
`reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994).
`Petitioner does not propose any constructions for claim terms in the
`claim construction section of the Petition. Pet. 16. However, in its analysis
`for element (d) of claim 1, Petitioner contends that “the broadest reasonable
`interpretation of ‘likely benefit of the at least one therapeutic agent’ is any
`therapeutic agent with potential efficacy.” Pet. 33 (citing Ex. 1002 ¶ 140).
`Additionally, Petitioner contends that “a POSA would understand claim
`element (d) not to require a therapeutic agent for any particular molecular
`target because claim element (d) only recites ‘at least one therapeutic agent’
`from the ‘listing of available therapeutic agents for the plurality of molecular
`targets.’” Id. at 33–34 (citing Ex. 1002 ¶ 141.).
`In this regard, Petitioner points out that the “specification discloses no
`drug-efficacy correlations for several of the genes listed in the claimed
`panel,” and that claim language of element (d) is open-ended due to the term
`
`
`1 A recent amendment to this rule changing the claim construction standard
`does not apply here because the Petition was filed before the November 13,
`2018, effective date. 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 (Oct. 11, 2018).
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`“compris[ing].” Id. at 34. Thus, reasons Petitioner, claim element (d) would
`be understood “to mean the claimed system has the computer-implemented
`capacity to access test and reference values in a database and to cross-
`reference molecular targets exhibiting a difference in test and reference
`values with a therapeutic agent database that includes information
`associating agents with one or more molecular targets.” Id. (citing Ex. 1002
`¶ 141).
`Patent Owner does not address the foregoing arguments in its
`Preliminary Response, nor does it propose any of its own claim
`constructions for other claim terms. Prelim. Resp. 16–17.
`As it is undisputed at this stage, we will accept Petitioner’s proposed
`interpretation of claim element (d) in our analysis as to whether there is a
`reasonable likelihood that Petitioner would prevail with respect to at least
`one challenged claim.2 We request the parties to further address this claim
`construction issue in their post-institution briefs.
`C. Obviousness Based on Lu and Illumina
`Petitioner contends that claims 1–14 are rendered obvious by the
`combined teachings of Lu and Illumina. Pet. 23–57. To support its
`contentions, Petitioner cites to Dr. Spellman’s declaration testimony
`(Ex. 1002). Patent Owner disagrees, and asserts that Illumina does not
`qualify as prior art. Prelim. Resp. 18–28. Patent Owner further contends
`
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`2 In this regard we note Petitioner’s currently unrebutted assertion, discussed
`infra, that “there were already therapeutic agent(s) with potential efficacy
`associated with each recited gene prior to May 18, 2006.” Pet. 34 n.7.
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`that the combination of Lu and Illumina fails to teach identifying cancer
`therapies independent of cancer type. Id. at 28–35. For the reasons
`provided below, we determine that Petitioner has demonstrated a reasonable
`likelihood of prevailing on its assertion that claims 1–14 are unpatentable
`based on the combination of Lu and Illumina.
`1. Overview of Lu
`Lu is an International Patent Application, published under the Patent
`Cooperation Treaty. Ex. 1004, (12). Lu discloses a “computerized decision
`support system for selecting the optimum treatment for human cancer.” Id.
`at (54). The system predicts “which of one or more drugs suitable to treat a
`cancerous condition in a patient are the optimum drug(s)” “based upon the
`particular patient’s genotype.” Id. at (57). According to Lu, the system
`comprises:
`a PCR kit and/or a gene chip designed to detect multiple genes,
`expressions and/or mutations associated with a particular cancer
`using a sample of the patient’s tissue or blood; a detector for
`accepting receipt of the gene chip toward analyzing the patient’s
`genotype; a database describing the correlation of patient
`genotypes and the efficacy and toxicity of various anti-cancer
`drugs used in treating patients with a particular cancerous
`condition; and a computerized decision support system operably
`connected to the detector for correlating the output of the detector
`to the database.
`Id. ¶ 18.
`Lu teaches that the detector outputs genetic data into a “bioinformatic
`software package” that compares the genetic data with “a database of data
`toward providing the physician with a recommendation into plain English in
`order to assist doctors to select the most effective medicine with the least
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`amount of side effects for patients.” Id. ¶ 42. Lu teaches that the software
`may be “customized for a single disease or multiple diseases.” Id.
`In a preferred embodiment, the system detects the breast cancer genes
`ER Alpha, Her2, ErbB1, BRAC1, and BRAC2. Id. ¶ 22. For example, the
`system detects upregulation or downregulation of the expression of those
`genes, or mutations in those genes. Id. ¶¶ 51, 53. Depending on the results,
`the system provides an output that recommends or discourages the use of
`certain drug(s) for cancer therapy. Id. ¶¶ 52, 54.
`2. Overview of Illumina
`Illumina is a technical bulletin prepared by Illumina, Inc. Ex. 1005.
`Illumina teaches that “[m]icroarray analysis of gene expression has proven
`to be a remarkable tool,” but has faced challenges because of the lack of
`high-quality and/or poor integrity RNA. Id. at 1 (Introduction). Illumina
`discloses a “gene expression assay for microarrays that is capable of
`utilizing partially degraded RNA.” Id.
`Specifically, Illumina discloses the “cDNA-mediated Annealing,
`Selection, extension and Litigation (DASL) Assay,” which “can monitor
`RNA expression of up to 1536 sequence targets.” Id. According to
`Illumina, “the DASL Assay offers researchers the opportunity to analyze
`hundreds to thousands of RNA transcripts derived from previously collected,
`preserved samples.” Id.
`Illumina discloses a particular DASL assay—the “DASL Cancer
`Panel”—that “is a pool of selected probe groups that targets 502 genes
`collected from ten publicly available cancer gene lists.” Id. at 4 (“The
`DASL Cancer Panel”). Illumina teaches that the “[g]enes were chosen
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`based on the frequency of appearance on these lists and the frequency of
`literature citations of these genes in association with cancer.” Id. The
`DASL Cancer Panel includes, among others, the genes EGFR, KIT, TOP1,
`MLH1, PTEN, PDGFRA and ESR1. Id. at Table 1.
`Illumina further teaches that the DASL assay can be used to analyze
`differential expression profiles, and provides an example comparing the
`expression of RNA from both normal prostate tissue and a prostate cancer
`cell line. Id. at 5. Illumina states that “expression analysis using degraded
`RNA will properly reflect biological differences measured using intact
`RNA.” Id. at 6. Illumina also teaches the DASL assay can be used to study
`differences in expression in clinical samples, to “report[] biologically
`relevant results.” Id. at 7 (“Application to Clinical Samples”).
`Finally, Illumina discloses that the DASL assay provides for high-
`throughput expression profiling, because it allows for the analysis of 16 or
`96 samples simultaneously. Id. at 8 (“Summary”).
`3. Prior Art Status of Illumina
`Under 35 U.S.C. § 311(b), a petitioner in an inter partes review may
`challenge the claims of a patent only on the basis of “prior art consisting of
`patents or printed publications.” At the institution stage, the Board has
`required the petitioner to make a “threshold showing” that any reference
`relied upon was publicly accessible prior to the effective filing date of the
`challenged patent. See, e.g., Frontier Therapeutics, LLC v. Medac
`Gesellschaft Für Klinische Spezialpräparate mbH, IPR2016-00649, slip op.
`at 22 (PTAB Sept. 1, 2016) (Paper 10) (denying trial institution upon finding
`that petitioner failed to make a threshold showing that an alleged “printed
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`package insert” was a printed publication); Instradent USA, Inc. v. Nobel
`Biocare Servs. AG, IPR2015-01786, slip op. at 16–17 (PTAB Feb. 19, 2016)
`(Paper 14) (finding that deposition testimony from the challenged patent’s
`co-inventor stating that hundreds of copies of a catalog may have been
`printed and distributed to customers was sufficient to make a threshold
`showing of public accessibility; granting trial institution).
`Here, we are persuaded that Petitioner has made the requisite
`threshold showing that Illumina is a prior art printed publication for
`purposes of institution. As noted by Petitioner, the Illumina reference itself
`bears indicia that it was likely published, including a publication date
`(November 16, 2005) and a publication number (470-2005-003). See
`Pet. 20; Reply 3–5. Moreover, Illumina is identified as a “technical
`bulletin,” akin to a product catalog, which “is the type of document intended
`for public dissemination, and it bears no designations, such as ‘draft’ or
`‘confidential,’ that might suggest that it was not intended for public
`distribution.” See Nobel Biocare Servs. AG v. Instradent USA, Inc., 903
`F.3d 1365, 1377 (Fed. Cir. 2018). In addition to the dates and markings on
`the document itself, Petitioner has pointed to the declaration of the Internet
`Archive’s Office Manager, Christopher Butler, attesting that the Illumina
`publication was archived by the Wayback Machine on December 27, 2005,
`and thereby confirming that it was publicly available. Ex. 1024, 5; Pet. 20;
`Reply 2–3.
`Patent Owner argues that the Butler declaration and attached
`Wayback Machine printouts are insufficient to establish the public
`accessibility of the Illumina reference because “Petitioner fails to mention
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`[the Butler declaration] anywhere in its Petition outside the exhibit list,” and
`this evidence should therefore not be considered in our institution analysis.
`Prelim. Resp. 21. We are not persuaded by this argument. As an initial
`matter, we observe that Petitioner cited to Exhibit 1024 in its Petition as the
`“Affidavit of Christopher Butler,” immediately after stating that “Illumina is
`prior art under § 102(a).” Pet. 20. Moreover, we gave the parties a
`sufficient opportunity to address the Butler declaration in additional briefing
`(both a Reply and Sur-Reply). Paper 8. We have considered the arguments
`presented in those briefs in determining whether Petitioner has made a
`sufficient showing for institution.
`Patent Owner further argues that, even if the Butler declaration were
`considered, it fails to show that the Illumina reference was available to
`persons of skill at the relevant time because there is no showing that the
`skilled artisan could have searched for, and found, the reference on the
`Internet without already having the exact URL where it was published.
`Prelim. Resp. 21–24. Patent Owner contends that there is no indication that
`the product page shown on the archived webpage (Ex. 1024, 4) linked
`directly to the version of the Illumina reference appearing in the Butler
`declaration (id. at 6–13). Prelim. Resp. 23. Patent Owner also contends that
`the Petition fails to meet the standard set forth in Blue Calypso, LLC v.
`Groupon, Inc., 815 F.3d 1331, 1349–50 (Fed. Cir. 2016). Prelim. Resp. 24–
`28; Sur-Reply 1.
`We do not interpret Federal Circuit precedent as suggesting that only
`certain types of evidence may be used to show public accessibility of a
`webpage. To the contrary, whether a reference is a “printed publication” is a
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`“case-by-case inquiry into the facts and circumstances surrounding the
`reference’s disclosure to members of the public.” Jazz Pharm., Inc. v.
`Amneal Pharm., LLC, 895 F.3d 1347, 1356 (Fed. Cir. 2018) (citing In re
`Klopfenstein, 380 F.3d 1345, 1350 (Fed. Cir. 2004)). In Jazz
`Pharmaceuticals, the Federal Circuit made clear that “neither indexing nor
`searchability” was required to determine that an online document was
`publicly accessible. Id. at 1359. Here, we find on the current record that the
`relevant public, including those skilled in the art, would have been generally
`aware that Illumina, Inc., offered research tools used for gene expression
`assays. See Ex. 1047, 2384 (describing Illumina’s DASL assay). That
`would seem to provide enough of a reason for anyone interested in the
`DASL assay to look at Illumina’s website, where technical bulletins such as
`the Illumina reference could be accessed.
`We find Patent Owner’s remaining arguments largely go to the
`question of whether Petitioner has met its ultimate burden of proving that the
`Illumina reference was publicly accessible. But we need not answer that
`question at this stage. Rather, based on the present record, we find that
`Petitioner has made a sufficient threshold showing that Illumina qualifies as
`a prior art printed publication for institution. To the extent Patent Owner
`continues to challenge the printed publication status of Illumina after
`institution, the parties may further develop the record on this issue. We will
`make our determination as to whether Petitioner has satisfied its burden of
`proving public accessibility in our final written decision based on the entire
`record.
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`Case 1:17-cv-12194-RGS Document 55-4 Filed 06/28/19 Page 18 of 33
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`IPR2019-00170
`Patent 9,372,193 B2
`
`
`4. Rationale for and Reasonable Expectation of Success in
`Combining Lu and Illumina
`Even “[i]f all elements of the claims are found in a combination of
`prior art references,” “the factfinder should further consider whether a
`person of ordinary skill in the art would [have been] motivated to combine
`those references, and whether in making that combination, a person of
`ordinary skill would have [had] a reasonable expectation of success.” Merck
`& Cie v. Gnosis S.P.A., 808 F.3d 829, 833 (Fed. Cir. 2015). The
`“motivation to combine” and “reasonable expectation of success” factors are
`subsidiary requirements for obviousness subsumed within the Graham
`factors. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1361 (Fed. Cir. 2007).
`Petitioner contends that an ordinarily skilled artisan would have had a
`reason to combine the teachings of Lu and Illumina, with a reasonable
`expectation of success, based on the teachings of the art, and based on the
`Lu and Illumina references themselves. Pet. 47–57. At this stage of the
`proceeding, Patent Owner does not provide specific arguments as to
`motivation to combine and reasonable expectation of success. See generally
`Prelim. Resp.
`Upon review of the record, we are satisfied that Petitioner has shown
`sufficiently for institution that an ordinarily skilled artisan would have had a
`reason to combine the disclosures of Lu and Illumina to provide an
`improved molecular-profiling system for identifying therapeutic drugs based
`on a patient’s genotype. The record reasonably supports Petitioner’s
`argument that, before May 18, 2006, “it was a common goal of many
`researchers in the field of personalized medicine to obtain comprehensive
`
`17
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`
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`Case 1:17-cv-12194-RGS Document 55-4 Filed 06/28/19 Page 19 of 33
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`IPR2019-00170
`Patent 9,372,193 B2
`
`molecular profiles of individuals to provide more effective diagnostic and
`therapeutic options” to patients. Pet. 48; see Ex. 1002 ¶¶ 112–13; Ex. 1050,
`27–28. The record also reasonably supports Petitioner’s argument that an
`ordinarily skilled artisan would have been aware of multiple techniques for
`obtaining molecular profile information, as well as multiple databases tying
`therapies to genetic markers. Pet. 48–49; see Ex. 1002 ¶¶ 114–115, 117;
`Ex. 1050, 30; Ex. 1051, 170–171.
`Finally, the record reasonably supports Petitioner’s argument that an
`ordinarily skilled artisan would have regarded RT-PCR assays as old
`technology, readily replaced by the more advanced DASL assay. Pet. 51–
`53; Ex. 1002 ¶ 119. Specifically, we rely on Dr. Spellman’s currently
`unrebutted testimony that the DASL assay was “capable of investigating a
`substantially larger number of molecular targets simultaneously than RT-
`PCR.” Ex. 1002 ¶ 119; see also Ex. 1047, 2386; Ex. 1053, 586; Pet. 52–53.
`Thus, in view of the background knowledge in the art and the specific
`teachings of Lu and Illumina, we are satisfied that this record supports a
`reasonable likelihood that an ordinarily skilled artisan would have been
`motivated to modify Lu’s system with Illumina’s DASL assay.
`We are also satisfied that the ordinarily skilled artisan would have had
`a reasonable expectation of success, given that the DASL assay was
`commercially available and apparently recognized in the art as useful for
`high-throughput expression analysis. See Pet. 54–57; see also Ex. 1002
`¶¶ 68, 182–186; Ex. 1050, 28–29, 31; Ex. 1046; Ex. 1047, 2386; Ex. 1048,
`1806; Ex. 1049, 878. We also observe that all the elements of molecular
`profiling systems were known, and required only ordinary skill to carry out.
`18
`
`
`
`Case 1:17-cv-12194-RGS Document 55-4 Filed 06/28/19 Page 20 of 33
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`IPR2019-00170
`Patent 9,372,193 B2
`
`See Pet. 56–57; see also Ex. 1002 ¶¶ 68, 186; Ex. 1037, Abstract; Ex. 1055,
`Abstract; Ex. 1051, 170, 172; Ex. 1032, 166, 169 (Table 2).
`5. Claim 1
`Petitioner asserts that each element of claim 1 is taught or suggested
`by the combination of Lu and Illumina. For example, Petitioner contends
`that Lu teaches “[a] system for generating a report identifying at least one
`therapeutic agent for an individual with a cancer” (Ex. 1001, 17:3–3), as
`recited in the preamble of claim 1. Specifically, Petitioner contends that Lu
`discloses identifying “which drugs are optimum to treat other cancerous
`conditions in patents” and providing a “computerized decision support
`system” for recommending the “optimum anti-cancer drug to prescribe for a
`patient” as objects of the invention. Pet. 23 (quoting Ex. 1004 ¶¶ 15–16
`(internal quotation marks omitted)).
`Element (a) of claim 1 calls for “at least one device configured to
`assay a plurality of molecular targets in a biological sample to determine
`molecular profile test values for the plurality of molecular targets, wherein
`the plurality of molecular targets comprises AR, EGFR, HER2, KIT, MLH1,
`PTEN, and PDGFRA.” Ex. 1001, 17:4–9. Petitioner asserts that the
`combination of Lu and Illumina teaches this claim element. Pet. 23–27. For
`example, Petitioner contends that Lu discloses a system for assaying a
`patient sample in order to produce test values for multiple targets by
`quantifying the up- and down-regulation of the targets. Id. at 24 (citing
`Ex. 1004 ¶¶ 18, 19, 22, 34, 35, 51, 52; Ex. 1002 ¶ 125). Petitioner also
`points out that Lu discloses assaying EGFR and HER2, two of the molecular
`targets recited in claim 1. Id. at 17–18, 25 (citing Ex. 1004 ¶¶ 22, 48, 51, 53,
`19
`
`
`
`Case 1:17-cv-12194-RGS Document 55-4 Filed 06/28/19
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