Paper No. 15
`
`
`Trials@uspto.gov
` Filed: May 6, 2019
`
`
`571.272.7822
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`NEPTUNE GENERICS, LLC,
`Petitioner,
`
`v.
`
`AVENTIS PHARMA S.A.,
`Patent Owner.
`____________
`
`Case IPR2019-00136
`Patent 5,847,170
`____________
`
`
`Before TINA E. HULSE, CHRISTOPHER M. KAISER, and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`MAJORS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314
`
`
`
`
`
`
`
`

`

`IPR2019-00136
`Patent 5,847,170
`
` INTRODUCTION
`Neptune Generics, LLC (“Petitioner”),1 on October 31, 2018, filed a
`Petition to institute inter partes review of claims 1 and 2 of U.S. Patent No.
`5,847,170 (Ex. 1001, “the ’170 patent”). Paper 1 (“Pet.”). Aventis Pharma
`S.A. (“Patent Owner”) filed a Preliminary Response to the Petition. Paper 9
`(“Prelim. Resp.”). We granted (Paper 11) Petitioner’s request to file a pre-
`institution Reply to Patent Owner’s Preliminary Response to address
`arguments related to discretionary denial of the Petition. Paper 13.
`Under 35 U.S.C. § 314(a), an inter partes review may not be instituted
`unless 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.” Upon considering the arguments and evidence, we determine
`that it is appropriate to exercise the Board’s discretion to deny institution
`under 35 U.S.C. § 325(d). Thus, as explained further below, we do not
`institute an inter partes review of claims 1 and 2 of the ’170 patent.
`
`
` BACKGROUND
`Related Matters
`A.
`Petitioner identifies litigation related to the ’170 patent including
`Sanofi-Aventis US LLC v. Fresenius Kabi USA, LLC, No. 14-7869 (D.N.J.
`filed Dec. 17, 2014).2 Pet. 8. According to Petitioner, “[a]pproximately one
`year ago the District of New Jersey held a bench trial on validity and
`infringement relating to the ’170 patent and certain Abbreviated New Drug
`
`
`1 Petitioner lists several entities as the real parties-in-interest. Pet. 7–8. We
`do not repeat that listing here.
`2 This case was consolidated for trial with several other pending cases.
`Ex. 1049, 1 n.1.
`
`2
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`IPR2019-00136
`Patent 5,847,170
`Applications.” Id. at 34–36; see also Prelim. Resp. 11–13 (stating that the
`’170 patent was the subject of “a Hatch-Waxman action before the District
`of New Jersey involving, at its peak, 10 defendants,” and ending in “an 8-
`day bench trial”). Petitioner further notes that the district court, at the trial’s
`conclusion, held that the ’170 patent’s claims had not been shown to be
`obvious. Pet. 34; Ex. 1049, 29, 83.
`Patent Owner states that “the district court defendants [from the
`litigation noted above] appealed and that appeal is now pending at the
`Federal Circuit.” Prelim. Resp. 14. According to Patent Owner, “the district
`court case has been completed, and the appeal of the district court’s decision
`upholding the ’170 patent is ready for oral argument at the Federal Circuit.”
`Id. at 28; see Sanofi-Aventis U.S., LLC v. Dr. Reddy’s Labs., Inc., No. 2018-
`1804 (Fed. Cir.).3
`As for related matters before the Board, Petitioner identifies an earlier
`challenge to claims 1 and 2 of the ’170 patent in Mylan Laboratories Limited
`v. Aventis Pharma S.A., IPR2016-00627 (filed Feb. 17, 2016). Pet. 9; see
`also Ex. 2011 (“Mylan Petition”). Petitioner notes the Board’s denial of
`institution of inter partes review in this earlier matter. Pet. 77–78; Ex. 2020
`(Aug. 23, 2016, Decision Denying Institution); see also Ex. 2021 (Jan. 26,
`2017, Decision Denying Petitioner’s Rehearing Request).
`
`
`3 Case Number 2018-1804 at the Federal Circuit is the lead case for other
`related appeals (Nos. 2018-1808 and 2018-1809), and involves the appeal of
`several district court cases that were consolidated for discovery and/or trial.
`See, e.g., Sanofi-Aventis U.S., LLC v. Dr. Reddy’s Laboratories, Inc., No.
`2018-1804, Document 68, 1–2 (Fed. Cir. filed Aug. 20, 2018). Oral
`argument before the Federal Circuit is scheduled for June 5, 2019. Sanofi-
`Aventis, No. 2018-1804, Document 116 (Notice of Oral Argument).
`3
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`

`IPR2019-00136
`Patent 5,847,170
`Notwithstanding the related matters above, Petitioner states that it
`“has never been accused of infringing the ’170 patent, nor has [Petitioner]
`previously filed IPR petitions against any related patents.” Pet. 78 n.3.
`
`
`The ’170 Patent and Background on Taxoids
`B.
`The ’170 patent, which issued December 8, 1998, relates to
`compounds known as “taxoids.” Ex. 1001, Abstract, 1:7. The ’170 patent’s
`taxoids have the following general formula (I):
`
`
`Ex. 1001, 1:7–28. The ’170 patent discloses that “radicals R4 and R5, which
`may be identical or different, represent unbranched or branched alkoxy
`radicals containing 1 to 6 carbon atoms.” Id. at 3:62–64. According to the
`’170 patent, “[t]he new [taxoid] products have antitumour properties, and
`more especially activity against tumours which are resistant to Taxol® or to
`Taxotere®.” Id. at 11:59–63 (“Such tumours comprise colon tumours which
`have high expression of the mdr 1 gene (multiple drug resistance gene).”).
`Taxol® is the trade name for the compound paclitaxel, a taxoid known in the
`
`4
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`

`IPR2019-00136
`Patent 5,847,170
`prior art. Ex. 1002 ¶ 71; Ex. 1009, 2; Ex. 1010, 1.4 Taxotere® is the trade
`name for another known taxoid, docetaxel, a semi-synthetic analog of
`paclitaxel. Ex. 1009, 2; Ex. 1011, 2.
`
`The claims of the ’170 patent challenged here are directed to a
`specific compound known as cabazitaxel and to compositions comprising
`the compound. Ex. 1001, 28:57–65 (claims 1 and 2); Pet. 1; Ex. 1002 ¶ 37.
`The chemical name for cabazitaxel is 4α-Acetoxy-2α-benzoyloxy-5β,20-
`epoxy-1β-hydroxy-7β,10β-dimethoxy-9-oxo-11-taxen-13α-yl(2R,3S)-3-tert-
`butoxycarbonylamino-2-hydroxy-3-phenlypropionate. Ex. 1001, 28:56–60;
`Ex. 1002 ¶¶ 36–37. Cabazitaxel’s chemical structure is shown below:
`
`
`Ex. 1002 ¶ 37 (annotations added). Relevant to the challenge in this
`Petition, we highlight in orange the two methoxy (OCH3) groups at the C-7
`and C-10 positions (R5 and R4, respectively in Formula I of the ’170 patent).
`We highlight in green the 3-tert-butoxycarbonylamino group (3'-NHBOC,
`which we refer to herein as a “BOC” group) at the C-3' position of the
`
`
`4 For purposes of the citations to the prior art (e.g., Exs. 1009, 1010, etc.),
`we refer to the page numbers provided on the exhibit copies, rather than the
`references’ original page numbering.
`
`5
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`IPR2019-00136
`Patent 5,847,170
`compound’s side chain (Formula II), the side chain being attached at C-13.
`See Prelim. Resp. 4 (showing side chain and core portions of cabazitaxel).
`
`We also reproduce below the chemical structures of two known and
`widely-studied taxoids, Taxol®/paclitaxel and Taxotere®/docetaxel, and
`discuss the structural differences between those compounds and cabazitaxel.
`
`
`Pet. 17; Ex. 1002 ¶ 72. Paclitaxel’s structure is shown above and includes,
`compared to cabazitaxel, different substituents at C-7, C-10, and at the C-3'
`position on the side chain. Paclitaxel has a benzoyl group attached to the
`nitrogen at C-3', not the BOC group as in cabazitaxel. Pet. 2. Paclitaxel also
`includes an O-acetyl/acetate (CH3COO) group at C-10 and a hydroxyl group
`(OH) at C-7, not methoxy groups at those positions like cabazitaxel. Id.
`Docetaxel, on the other hand, includes the same BOC-containing side
`chain as cabazitaxel, as illustrated in the chemical structure below.
`
`6
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`

`IPR2019-00136
`Patent 5,847,170
`
`
`Ex. 1002 ¶ 98 (Decl. Fig. 8 (partial)). Docetaxel, like paclitaxel, differs
`from cabazitaxel’s structure at the C-7 and C-10 positions. As shown above,
`docetaxel includes hydroxyl groups at both C-7 and C-10—not the methoxy
`groups at those positions as in cabazitaxel. See Ex. 2020, 5–6 (comparing
`structures for cabazitaxel, paclitaxel, and docetaxel).
`
`By the mid–1990s, and before the earliest putative priority date of the
`’170 patent, it was well-known that taxanes,5 especially paclitaxel and
`docetaxel, have significant anticancer properties. Ex. 1002 ¶ 48. Those
`properties derive from the ability of such taxanes to stabilize microtubules
`and, thus, disrupt the rapid division of cancerous cells undergoing mitosis.
`Id. ¶¶ 48, 74–75; Ex. 1009, 2; Ex. 1010, 1; Ex. 1010, 2.
`
`Paclitaxel was the first formally isolated taxane and, by the 1970s, its
`structure and ability to inhibit cancerous cell growth were reported in the
`literature. Ex. 1002 ¶¶ 71–73; Ex. 1009, 2; Ex. 1008, 2. Although paclitaxel
`was initially isolated from the bark of the yew tree (Taxus brevifolia), the
`extraction process produced low yields and was fatal to the tree, limiting
`
`
`5 Taxane diterpinoids (like paclitaxel, docetaxel, and cabazitaxel) are also
`known as taxoids. Ex. 1009, 2. We may, at times herein, use the terms
`taxane and taxoid interchangeably.
`
`7
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`

`IPR2019-00136
`Patent 5,847,170
`supply. Ex. 1002 ¶ 80; Ex. 1009, 2; Ex. 1010, 2. By the early 1990s,
`however, researchers had discovered that paclitaxel and docetaxel could be
`produced through a process that started with a naturally-occurring and
`abundant semi-synthetic precursor, 10-deacetyl baccatin III (“10-DAB-III”),
`which could be isolated from the needles of the yew tree without killing the
`tree. Pet. 18–19; Ex. 1002 ¶¶ 83–86, 93–96; Ex. 1009, 2–3.
`The chemical structure of 10-DAB-III is shown below.
`
`
`Pet. 3; Ex. 1002 ¶ 87. As illustrated in the structure above, 10-DAB-III
`contains the tetracyclic core of paclitaxel and docetaxel, but includes a
`hydroxyl group (red circle) at C-10 rather than paclitaxel’s acetate group at
`that position. Pet. 3; Ex. 1002 ¶ 88. And, as illustrated above, 10-DAB-III
`lacks a side chain at C-13—either with the benzoyl group at C-3' like
`paclitaxel, or with the BOC group at C-3' like docetaxel. Pet. 18–19
`(showing side-chain and C-10 acetate addition to 10-DAB-III to arrive at
`paclitaxel), 25 (showing addition of BOC-containing side-chain to 10-DAB-
`III to arrive at docetaxel). The ’170 patent also describes processes that use
`10-DAB-III as an advanced precursor for synthesizing the allegedly new
`taxoid compounds. See, e.g., Ex. 1001, 7:23–38.
`
`
`8
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`

`IPR2019-00136
`Patent 5,847,170
`
`Challenged Claims
`C.
`Petitioner challenges claims 1 and 2, which read as follows:
`1.
`4α-Acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-
`7β,10β-dimethoxy-9-oxo-11-taxen-13α-yl(2R,3S)-3-tert-
`butoxycarbonylamino-2-hydroxy-3-phenlypropionate.
`
`A pharmaceutical composition comprising at least the
`2.
`product according to claim 1 in combination with one or more
`pharmaceutically acceptable diluents or adjuvants and optionally
`one or more compatible and pharmacologically active
`compounds.
`
`
`Ex. 1001, 28:57–65.
`
`
`The Asserted Grounds of Unpatentability
`D.
`Petitioner contends that claims 1 and 2 are unpatentable based on the
`grounds in the table below. Pet. 16.
`
`Grounds References
`1
`Commerçon,6 Kant,7 and Wong8
`
`Commerçon, Kant, Wong, and Bouchard9
`
`2
`
`Basis Claims
`§ 103
`1 and 2
`
`§ 103
`
`
`1 and 2
`
`
`
`6 A. Commerçon et al., Practical Semisynthesis and Antimitotic Activity of
`Docetaxel and Side-Chain Analogues, in TAXANE ANTICANCER AGENTS
`(Chapter 17), 233–246 (Georg, G. et al. ed., American Chemical Society
`Symposium Series, 1994). Ex. 1009 or “Commerçon.”
`7 Joydeep Kant et al., A Chemoselective Approach to Functionalize the C-10
`Position of 10-Deacetylbaccatin III. Synthesis and Biological Properties of
`Novel C-10 Taxol® Analogues, 35 TETRAHEDRON LETTERS 5543 (1994).
`Ex. 1010 or “Kant.”
`8 Wong et al., US 6,201,140 B1, issued Mar. 13, 2001. Ex. 1011 or “Wong.”
`9 Bouchard et al., US 5,587,493, issued Dec. 24, 1996. Ex. 1014 or
`“Bouchard.”
`
`9
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`IPR2019-00136
`Patent 5,847,170
`Petitioner also relies on the Declaration of John L. Wood, Ph.D.
`(Ex. 1002), among other evidence.
` ANALYSIS
`A. Overview of the Asserted References
`We provide overviews of Commerçon, Kant, and Wong below.10
`1. Commerçon (Ex. 1009)
`Commerçon relates to synthesis of docetaxel and docetaxel side-chain
`analogs. Ex. 1009, 2, 12. Commerçon discloses that “[s]tructure-activity
`relationship studies demonstrate that biological activity is very dependent on
`the position and nature of substituents on the aromatic ring of 3'-modified-
`phenyl analogs.” Id. at 2. Commerçon discloses that “tert-butoxycarbonyl
`[i.e., BOC] remains the substituent of choice for the 3'-nitrogen atom” and
`teaches that, among the new taxoids studied, “3'-para-fluoro-docetaxel was
`identified as one of the most powerful analogs of docetaxel.” Id.; see also
`id. at 12.
`Commerçon notes that, compared to paclitaxel, docetaxel includes a
`BOC group instead of a benzoyl group on the C-3' nitrogen atom and
`includes a hydroxyl function instead of paclitaxel’s acetate at the C-10
`position. Ex. 1009, 3. According to Commerçon, “[t]hese structural
`
`
`10 Petitioner’s reliance on Bouchard relates principally to the teaching that
`lipophilic taxanes may be formulated with known adjuvants or excipients.
`Pet. 32–33. Petitioner, for Ground 2, relies on Bouchard to address those
`elements added in dependent claim 2. Pet. 59–61. For Ground 1, which
`does include Bouchard, Petitioner challenges claim 2 over the combination
`of Commerçon, Kant, and Wong, and a skilled person’s knowledge that
`formulating lipophilic taxanes (like paclitaxel) with solubility-enhancing
`adjuvants or excipients was a “customary” technique as described in the
`’170 patent and other art generally. Pet. 57–58.
`10
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`

`IPR2019-00136
`Patent 5,847,170
`modifications [on docetaxel] lead to an increase of cytotoxicity in certain
`experimental models,” and thus, “[t]hese results suggested the possibility of
`further improvement by introducing, for instance, new side-chain
`modifications.” Id.
`Commerçon also includes Figure 2, reproduced below, as illustrating
`“present knowledge” related to structure-activity relationships for taxoids.
`Id. at 3 (“Structure-activity relationships of taxoids have already been
`reviewed . . . and our present knowledge in this area can be outlined as
`depicted in figure 2.”) (citations omitted).
`
`
`
`
`
`Id. at 4. Figure 2 indicates, inter alia, that the substituent at the 3' nitrogen
`on the side chain is “flexible” and including a BOC group provides greater
`cytotoxicity than a benzoyl group at that position (“Boc > PhCO”). Id.
`According to Commerçon, other portions of the molecule are also
`“flexible” and can be modified without a significant effect on cytotoxicity.
`
`11
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`

`IPR2019-00136
`Patent 5,847,170
`Id. at 3–4. For example, Commerçon states that a “wide number of
`modifications can be introduced at the 7-position without significant loss of
`activity.” Id. Commerçon discusses certain other known and potential
`modifications (e.g., at C-9, C-19, etc.) and states that “the top part of the
`diterpene moiety, that is positions 7, 9, 10 and 19, tolerate a wide variety of
`substituents,” and “[t]his allows us to assume that this region of taxoids may
`not play a crucial role in microtubule binding or, to some extent, to
`cytotoxicity.” Id. at 4.
`After summarizing other known structure-activity relationship studies,
`Commerçon states that “[t]hese preliminary results suggested that other
`modifications at C-3' might further improve the antitumor efficacy.” Id. at
`5. Commerçon then reports “[Commerçon’s] results regarding the
`stereoselective semisynthesis of docetaxel and new taxoids with either a 3'-
`modified-phenyl ring or a 3'-N-modified-carbamate moiety, along with their
`biological activity.” Id. at 5–12.
`2. Kant (Ex. 1010)
`Kant relates generally to the synthesis and properties of paclitaxel
`analogues, having different groups at the C-10 position. Ex. 1010, 1. As
`explained in Kant, the authors “were interested in replacing the C-10 acetate
`moiety [of paclitaxel] with other functionalities.” Id. As with the synthesis
`of paclitaxel, Kant discloses that “10-DAB [10-deacetyl baccatin III] was
`envisioned to be the ideal starting material” for synthetic and
`“chemoselective” manipulations at the C-10 position and the synthesis of
`Kant’s analogues. Id.; see also id. (teaching “the side chain can always be
`introduced at a later stage by using a variety of published procedures”).
`Further to Kant’s chemoselective synthesis, Kant discloses that, “with
`the more reactive C-7 hydroxyl protected, an opportunity was available to
`
`12
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`

`IPR2019-00136
`Patent 5,847,170
`selectively deprotonate the C-10 hydroxyl.” Id. at 2. By protecting the C-7
`position, Kant discloses that one can “introduce a variety of functionalities
`(esters, ethers, carbonates . . .) at the C-10 position of baccatin in moderate
`to high yields.” Id.
`Kant discloses that several “[a]ll new analogues were evaluated in
`tubulin polymerization[] and in-vitro cytotoxicity assays performed using
`the HCT 116 human colon carcinoma cell lines.” Id. at 3. The results of this
`evaluation are reported in Kant’s Table II. Id. (Table II (showing results for
`Taxol®/paclitaxel (compound 1)11 and ten analogues)).
`Among the compounds evaluated is analogue number 20 (hereafter
`“Kant compound 20”), which includes a methoxy group at C-10, a C-7
`hydroxyl, and a BOC-containing side chain. Id. at 3. Kant discloses that
`“[a]ll new compounds displayed cytotoxic properties,” but “[a]nalogues with
`C-10 methyl ether ([compound] 20) or methyl carbonate (22) with
`TaxotereTM side chain (i.e., 3'-NHBOC) were found to be more cytotoxic
`than paclitaxel (1) or 10-acetyl taxotere (15).” Id. at 4. (“These compounds
`[20 and 22] also exhibited better tubulin binding properties.”). Kant further
`discloses that “with the paclitaxel side chain, the corresponding C-10
`modifications resulted in analogues (19 & 21) exhibiting tubulin binding
`similar to paclitaxel but less cytotoxic than the parent compound, with the
`exception of C-10 carbamate (18), which was found to be more potent than
`paclitaxel.” Id. Kant concludes that, “[i]n view of our studies, it is
`reasonable to suggest that the functional group present at the C-10 position
`
`
`11 Table II indicates that Taxol® includes a “Ph” (phenyl) moiety at R1 (R1
`being attached to an oxygen, which itself is attached to C-10). Ex. 1010, 3.
`This is an apparent typographical error, as Taxol® has an acetyl group at
`R1/C-10 as elsewhere described in Kant. Id. at 1–2; Ex. 1002 ¶ 179.
`13
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`

`IPR2019-00136
`Patent 5,847,170
`does modulate the antitumor activity, which is quite contrary to some of the
`earlier predictions.” Id.
`3. Wong (Ex. 1011)
`Wong relates generally to taxane derivatives and their use as
`antitumor agents. Ex. 1011, Abstract. More specifically, Wong discloses
`“taxane derivatives having the formula (I)” as shown below.
`
`
`Id. at 2. Wong teaches that R1 in formula (I) may comprise a variety of
`substituents such as hydrogen, a C1-8 alkyloxy, or C2-8 alkenyloxy. Id. When
`R1 is hydrogen, a methoxy group is at the molecule’s C-7 position.
`According to Formula (I), an acetate moiety (“OAc”) is at the C-10 position.
`
`Wong exemplifies 22 compounds of formula (I), one of which is
`Example 2, depicted below.
`
`14
`
`
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`

`IPR2019-00136
`Patent 5,847,170
`Ex. 1011, 12 (annotations added). The compound depicted in Example 2
`above includes a methoxy group (OCH3) at the molecule’s C-7 position.
`Like docetaxel, the Example 2 compound includes a BOC group attached to
`the nitrogen atom at the 3'-C position on the side chain. And, like paclitaxel,
`the Example 2 compound includes an acetate substituent (AcO) at C-10.
`
`Wong also discloses a study on hybrid mice implanted with M109
`lung carcinoma. Ex. 1011, 5–6. The mice were grouped and treated with
`some of the exemplary compounds via “intraperitoneal injection of various
`doses on days 5 and 8 post-tumor implant,” and one group remained
`untreated as a control. Id. at 6. The mice were followed for daily survival.
`Id. The results, specifically median survival times, are reported in Table 1.
`Id. (Table 1, providing results for ten example compounds, including
`Example 2). Wong concludes that “[c]ompounds of formula (I) . . . are
`effective tumor inhibiting agents, and thus are useful in human and/or
`veterinary medicine.” Id.
`
`Person of Ordinary Skill in the Art
`B.
`Petitioner proposes the following qualifications for the person of
`ordinary skill in the art:
`A POSA at the relevant time would possess the following
`qualifications: (a) a Ph.D. in organic chemistry, medicinal
`chemistry, or a closely related discipline, or (b) a master’s degree
`in organic chemistry, medicinal chemistry, or a closely related
`discipline, and at least two years of practical experience
`synthesizing and characterizing drug molecules.
`Pet. 33–34. Patent Owner agrees with this proposal, but adds that the
`ordinarily skilled person may also have “a bachelor’s degree in chemistry, or
`a closely related discipline, and at least four years of practical experience
`synthesizing and characterizing drug molecules.” Prelim. Resp. 14–15.
`
`15
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`IPR2019-00136
`Patent 5,847,170
`For this Decision, we adopt Petitioner’s proposal. We do not,
`however, discern a substantive difference between the proposals that would
`affect our analysis. We also find that the relied-upon prior art demonstrates
`the level of skill in the art at the time of the invention. Okajima v.
`Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (explaining that specific
`findings regarding ordinary skill level are not required where the prior art
`reflects an appropriate level and a need for testimony is not shown).
`
`
`Claim Construction
`C.
`In an inter partes review, we interpret claim terms in an unexpired
`patent12 based on the broadest reasonable construction in light of the
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b)
`(2018); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016)
`(affirming the broadest reasonable construction standard in inter partes
`review proceedings).13 Under that standard, we presume a claim term
`carries its “ordinary and customary meaning,” which “is the meaning that
`the term would have to a person of ordinary skill in the art in question” at
`the time of the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257
`
`
`12 Patent Owner appears to have obtained a term extension for the ’170
`patent related to FDA approval for Jevtana® (cabazitaxel). See Patent Term
`Extension Certificate dated Feb. 4, 2014; see also Notice of Final
`Determination dated Oct. 20, 2013 (indicating expiration on Mar. 26, 2021).
`13 The Final Rule changing the claim construction standard in IPR
`proceedings does not apply here, as the Petition was filed before the rule’s
`effective date, 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, 51,344 (Oct. 11, 2018). But, we do
`not perceive on this record that the construction of the challenged claims
`would be different depending on which standard is applied.
`16
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`

`IPR2019-00136
`Patent 5,847,170
`(Fed. Cir. 2007). We need only construe terms in controversy, and only to
`the extent necessary to resolve that controversy. Vivid Techs., Inc. v. Am.
`Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999); see also Nidec Motor
`Corp. v. Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed.
`Cir. 2017) (applying Vivid Techs. in the context of an inter partes review).
`There is no claim construction dispute raised in this Petition.
`Petitioner states that the claims have their ordinary meaning and “do not
`require interpretation.” Pet. 15. Patent Owner, for its part, states that “no
`term in claims 1 or 2 of the ’170 patent requires construction.” Prelim Resp.
`15. So, for this Decision, we conclude that no express construction beyond
`the claim language itself is necessary.
`
`D. History of the ’170 Patent at the U.S. Patent Office and in Other
`Legal Proceedings
`1. Prosecution History
`On April 29, 1997, the Examiner rejected then-pending claim 17
`(issued claim 1) as obvious over the taxanes in U.S. Patent No. 5,229,526
`(“Holton ’526”) in combination with “Greene.” Ex. 1004 (file history),
`725–726; Ex. 1001, [56] (identifying, among the references cited, “Greene et
`al., “Protective Groups in Organic Synthesis,” pp. 10–14, 2nd edition, 1991).
`According to the Examiner, although Holton ’526 did “not specifically teach
`the instant R4 and R5 [i.e., C-10 and C-7] groups,” the Examiner determined
`that Greene taught “the instant hydroxy protecting groups [methoxy groups]
`to be conventional.” Ex. 1004, 727.
`Applicants responded on October 29, 1997 with a declaration from
`one of the named inventors, Dr. Alain Commerçon. Ex. 1004, 665–666; see
`also id. at 680–689 (Oct. 23, 1997 Commerçon Decl.). Applicants argued
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`“that methoxy groups . . . at the 7- and 10-positions of the claimed
`compounds cannot be considered appropriate hydroxy protecting groups in
`taxane compounds under conditions for removing hydroxy-protecting
`groups” described in Holton ’526. Id. at 667. Applicants argued that
`Dr. Commerçon’s testing showed “that when the 7,10-dimethoxy Test
`Compound is subjected to the mildly acidic conditions such as used in
`Holton . . . to deprotect taxane compounds . . . no removal of the methoxy
`groups of the Test Compound is observed.” Id. at 670–671.
`The Examiner responded on February 25, 1998, maintaining the
`rejection for obviousness, and adding U.S. Patent No. 5,489,601 (“Holton
`’601”) to the combination of Holton ’526 and Greene. Id. at 618–619.
`According to the Examiner, Holton ’601 “teaches an analogous taxane
`wherein the C-7 and C-10 positions contain an alkoxy groups . . . [and] [i]t
`would have been prima facie obvious to replace the disclosed hydroxy
`protecting group of Holton [’526] with the hydroxy protecting groups as
`taught by Greene et al and Holton et al [i.e., Holton ’601] to form the
`claimed compounds without the loss of the same utility.” Id. at 619.
`Applicants responded on April 23, 1998 with a second declaration
`from Dr. Commerçon. Id. at 589, 613–615. According to Applicants,
`Dr. Commerçon’s second declaration provided testing data for compounds
`with and without methoxy groups at C-7 and C-10, and such testing
`allegedly showed “unexpectedly superior” properties with the compound of
`claim 17. Id. at 615; see also id. at 580–587 (April 23, 1998 Commerçon
`Decl.). In a Supplemental Response, Applicants also repeated their
`argument that methoxy groups could not serve as protecting groups at C-7
`and C-10 of Holton’s taxoids, and stated that the comparative testing was
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`offered merely “in support of an alternative argument.” Id. at 326–327 (Apr.
`27, 1998, Supplemental Response).
`Then, following an interview with the Examiner, Applicants provided
`“Further Supplemental Remarks” on May 28, 1998. Id. at 298. Applicants
`stated that “[t]he purpose of the Supplemental Remarks” included
`“bring[ing] additional evidence to the Examiner’s attention to further
`support Applicants’ position that the methyl groups at the 7- and 10-position
`of the compound recited in claim 17 are not hydroxy protecting groups.” Id.
`at 298–299. This additional evidence included citation and discussion
`related to two published European patent applications (EP 0 694 539 A1
`(“EP ’539”) and EP 0 604 910 A1 (“EP ’910”)).14 Id. at 299–302.
`Applicants asserted that “these two EP applications are quite similar to the
`disclosures of EP 639 577 (EP ‘577) and the Kant article in Tetrahedron
`Letters [(Ex. 1010, “Kant”),] which were cited in an Information Disclosure
`Statement on June 26, 1996.” Id. at 299. Even if the references suggested
`methyl and methyl ether groups may be included at C-7 or C-10, Applicants
`nevertheless asserted that none of the references supported a finding that
`such groups, rather than being part of the final product, could or should
`function as removable hydroxy-protecting groups at those positions. Id. at
`300–302. Applicants further explained that “the methyl groups at the 7- and
`10-positions of the compound recited in claim 17 are not intended to be
`
`
`14 EP ’539 is the European counterpart to the U.S. patent application that
`issued as Wong (Ex. 1011). Prelim. Resp. 8. The Supplemental Remarks
`mis-number EP ’539 as EP 0 684 539, not EP 0 694 539. Ex. 1004, 299. A
`copy of EP ’539, however, appears to have been submitted (Ex. 1004, 548)
`and the correct application number for EP ’539 is identified in the IDS
`submitted by Applicants, which the Examiner initialed (id. at 293–295).
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`removed, i.e., converted to an H.” Id. at 301. Hence, according to
`Applicants, the cited publications “further support Applicants’ position that
`the methyl groups at the 7- and 10-position of the compound recited in
`claim 17 are not hydroxy protecting groups.1” Id. at 299–300, 302.15
`On June 9, 1998, the Examiner entered a Notice of Allowability for
`claims 17 and 40 (issued claims 1 and 2), along with other pending claims.
`Ex. 1004, 292. The Examiner provided no further comment on the
`Applicants’ arguments and gave no specific reasons for allowance. Id.
`2. Prior Petition for Inter Partes Review
`The Mylan Petition (see supra, Section II(A)) also challenged
`claims 1 and 2 of the ’170 patent as being unpatentable for obviousness. Ex.
`2011, 13–14. The two grounds advanced in the Mylan Petition are shown in
`the table below:
`
`
`
`
`
`
`15 In footnote 1 of the Supplemental Remarks, Applicants stated that neither
`the cited applications (EP ’539 or EP ’910), nor other art of record,
`remotely teaches or suggests the compound recited in present
`claim 17 which recites methoxy groups at both the 7- and 10-
`positions. In these references, the 7- and 10- positions do not
`overlap. Thus, there is no suggestion in these applications that
`the substituents at the 7- and 10- positions can be the same, let
`alone that they can both be methoxy.
`Ex. 1004, 300 n.1.
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`Grounds References
`1
`Kant and Klein16
`
`Colin,17 Kant, and Klein
`
`2
`
`Basis Claims
`§ 103
`1 and 2
`
`§ 103
`
`
`1 and 2
`
`Ex. 2011, 14.
`For Ground 1, Mylan cited Kant’s disclosure of paclitaxel and
`docetaxel analogues and, relying on Kant compound 20 and its favorable
`tubulin binding and cytotoxic properties, Mylan argued it would have been
`obvious to select that compound for modification. Id. at 2011, 5–6, 31.
`Although Kant compound 20 differed from the compound of claim 1
`of the ’170 patent at only one position—including a hydroxyl group at C-7,
`rather than claim 1’s methoxy group—Mylan argued that a methoxy
`substitution at C-7 was made obvious by Klein’s teachings. Ex. 2011, 32.
`More specifically, Mylan asserted that Klein’s analogous taxoid compounds
`having a methoxy group at C-7 significantly increased antitumor potency
`versus compounds with a hydroxyl group at that position (as in Kant’s
`compound 20). Id. As for other substitutions described in Klein,
`particularly reduction of the carbonyl (CO) at C-9, Mylan argued the skilled
`artisan would not make such a change because it required a more complex
`process and additional synthetic steps, and Klein disclosed that it resulted in
`compounds with reduced potency against cancer cells. Id. at 34.
`
`
`16 L. L. Klein et al., Chemistry and Antitumor Activity of 9(R)-
`Dihydrotaxanes, in TAXANE ANTICANCER AGENTS (Chapter 20), 276–287
`(Georg, G. et al. ed., American Chemical Society Symposium Series, 1994).
`Ex. 101