Trials@uspto.gov Paper No. 11
`571-272-7822
`
` Date: April 23, 2021
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`ETON PHARMACEUTICALS, INC.,
`Petitioner,
`v.
`
`EXELA PHARMA SCIENCES, LLC,
`Patent Owner.
`____________
`
`PGR2020-00086
`Patent 10,653,719 B1
`____________
`
`
`
`Before ULRIKE W. JENKS, SUSAN L. C. MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
`
`
`
`
`
`
`571-272-7822
`
` Date: April 23, 2021
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`ETON PHARMACEUTICALS, INC.,
`Petitioner,
`v.
`
`EXELA PHARMA SCIENCES, LLC,
`Patent Owner.
`____________
`
`PGR2020-00086
`Patent 10,653,719 B1
`____________
`
`
`
`Before ULRIKE W. JENKS, SUSAN L. C. MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
`
`
`
`
`
`
`
`PGR2020-00086
`Patent 10,653,719 B1
`
`Eton Pharmaceuticals Inc. (“Petitioner”) filed a Petition requesting a
`post-grant review of claims 1–27 (“the challenged claims”) of U.S. Patent
`10,653,719 B1(Ex. 1106, “the ’719 patent”). Paper 1 (“Pet.”). Exela Pharma
`Sciences, LLC (“Patent Owner”) filed a Preliminary Response to the
`Petition. Paper 6 (“Prelim. Resp.”). With our authorization (see Ex. 1124 at
`14–20), Petitioner filed a reply to Patent Owner’s Preliminary Response
`(Paper 8 (“Pet. Reply”)), and Patent Owner filed a Sur-reply (Paper 10
`(“Sur-reply”)). We granted the additional briefing to allow Petitioner to file
`a copy of the request for rehearing it filed in related proceedings, PGR2020-
`00064 and PGR2020-00068, and to respond to assertions made in Patent
`Owner’s Preliminary Response.
`We have authority to determine whether to institute a post-grant
`review. 35 U.S.C. § 324. After considering all the papers submitted and cited
`evidence, for the reasons discussed below, we deny the Petition and do not
`institute a post-grant review.
`I.
`Real Parties in Interest
`Petitioner identifies itself as the real party in interest. Pet. 2. Patent
`Owner identifies itself as the real party in interest. Paper 3, 2.
`B.
`Related Proceedings
`The parties identify a related litigation matter, Exela Pharma
`Sciences, LLC v. Eton Pharms., Inc., Case No. 1:20-cv-00365-MN (D. Del.,
`filed March 16, 2020) (the “District Court Action”). Pet. 2; Paper 3, 2.
`The parties also identify U.S. Patent No. 10/478,453, which is the
`subject of a post-grant review in PGR2020-00064, U.S. Patent No.
`10,583,155, which is the subject of a post-grant Review in PGR2020-00068.
`
`BACKGROUND
`
`A.
`
`2
`
`
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`PGR2020-00086
`Patent 10,653,719 B1
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`Pet. 3–4; Paper 3, 2. The parties also identify related applications U.S. Patent
`Appl. No. 16/746,028, U.S. Patent Appl. No.16/773,641, U.S. Patent Appl.
`No.16/850,726, U.S. Patent Appl. No.16/850,962, and U.S. Patent Appl.
`No.16/850,973. Pet. 3–4; Paper 3, 3.
`C.
`The ’719 Patent (Ex. 1106)
`The ’719 patent is titled “STABLE, HIGHLY PURE L-CYSTEINE
`COMPOSITIONS FOR INJECTION AND METHODS OF USE.”
`Ex. 1106, code (54). The ’719 patent issued from Application No.
`16/773,563 (“the ’563 application”), filed January 27, 2020. Id. at (21), (22).
`The ’719 patent describes stable L-cysteine compositions for
`injection, comprising: L-cysteine or a pharmaceutically acceptable salt
`thereof and/or hydrate thereof in an amount from about 10 mg/mL to about
`100 mg/mL, and aluminum in an amount from about 1.0 parts per billion
`(ppb) to about 250 ppb. Id. at (57).
`“L-cysteine is a sulfur-containing amino acid that can be synthesized
`de novo from methionine and serine in adult humans.” Id. at 1:26–28.
`Because L-cysteine can be synthesized by the body, it is considered a non-
`essential amino acid. Id. at 1:33–34. “L-cysteine can be conditionally
`essential in preterm infants due to biochemical immaturity of the enzyme
`cystathionase that is involved in L-cysteine synthesis. Thus, there are a
`number of circumstances in which L-cysteine supplementation can be
`desirable.” Id. at 1:37–42.
`According to the specification, “[i]t has now been found that L–
`cysteine compositions for injection can be prepared using the methods
`described herein whereby the compositions unexpectedly comprise
`exceedingly low levels of Aluminum and other undesirable impurities, such
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`Patent 10,653,719 B1
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`as cystine, pyruvic acid, certain heavy metals and certain ions.” Id. at 4:37–
`43. Moreover, the specification discloses that:
`[T]he problems of safety, purity and stability are results not
`simply or directly from the level of Aluminum, but are also
`intertwined with dissolved oxygen levels in the composition
`and oxygen in the headspace as well as certain heavy metals
`and certain ions that may leach or be extracted out of the
`container closure.
`Id. at 4:51–56.
`The specification discloses that “known L-cysteine compositions
`contain up to 5000 ppb Aluminum.” Id. at 7:21–22. In contrast, the
`specification describes “compositions that provide a therapeutically effective
`amount of L-cysteine, while containing less than 250 ppb Aluminum.” Id. at
`7:25–26. The specification discloses that reduced aluminum compositions
`“permit[ ] exposure to less than or equal to 4–5 micrograms per kilogram per
`day (μg/kg/d) to avoid or minimize Aluminum toxicity while still providing
`therapeutically effective L-cysteine in a stable composition.” Id. at 7:35–38.
`The specification expressly defines the term “stable.”
`the term “stable” refers to a composition that has the component
`profiles described herein, for example. Aluminum, L-Cystine,
`and pyruvic acid, at the levels described and for the amount of
`time identified. In other words, a stable composition will
`coma.in the specified levels of all componentsfor [a] sufficient
`period of time to enable the composition to be commercially
`manufactured, stored, shipped, and administered in a clinical
`setting.
`Id. at 16:41–48. For example, the specification discloses compositions
`wherein “cystine is present in the composition in an amount not more than
`2.0 wt % relative to L-cysteine after storage at ambient temperature for a
`period of 6 months.” Id. at 25:6–9. The specification also discloses
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`Patent 10,653,719 B1
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`compositions wherein “pyruvic acid is present in the composition in an
`amount not more than 2.0 wt % relative to L-cysteine after storage at
`ambient temperature for a period of 6 months.” Id. at 26:5–8.
`Example 1 of the ’719 patent describes a method of compounding an
`L-cysteine composition. See id. 41:60–42:32. Example 2 describes a test for
`aluminum levels in L-cysteine injections compounded as per Example 1. Id.
`at 42:34–60. The bulk solution was filled into uncoated Schott Type 1 USP
`glass vials. Id. Although “[t]he product was quite stable for all the time
`points tested up to 12 months[,] . . . the product resulted in an unacceptably
`high aluminum content.” Id. at 42:43–49. The aluminum levels are shown in
`Table 6, reproduced below. Id.
`
`TABLE 6
`Aluminum Levels
`
`
`
`6 Months
`
`40°
`25°
`Release
`Lot #
`C./75% RH
`C./60% RH
`1,306 ppb
`569 ppb
`212 ppb
`XMHH1609
`1,374 ppb
`748 ppb
`199 ppb
`XMHH1610
`1,044 ppb
`726 ppb
`230 ppb
`XMHH1611
`Example 6 also describes the stability of L-cysteine injections
`compounded as per Example 1. Id. at 49:55–50:22. The bulk solution was
`filled into Schott Type 1 USP Plus glass, which is internally coated with
`silicon dioxide. Id. Unlike Example 2, the L-cysteine compositions stored in
`coated glass vials did not show increased aluminum content when stored
`upright at room temperature for 9 months at 25° C/60% RH. Id. The stability
`data is shown in Table 18, reproduced-in-part below. Id.
`TABLE 18
`Characterization of L-Cysteine Composition for Injection
`Test
`XMHJ1705
`XMHJ1706
`XMHJ1707
`
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`PGR2020-00086
`Patent 10,653,719 B1
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`L-Cysteine HCl
`
`Up
`100.4%
`
`0.3%
`0.1%
`3.2 ppb
`
`Up
`101.3%
`
`0.3%
`0.2%
`2.9 ppb
`
`Up
`101.2%
`
`0.3%
`0.1%
`5.6 ppb
`
`Related Compounds
`L-Cystine
`Pyruvic Acid
`Aluminum Content
`D.
`Illustrative Claim
`Claim 1 of the ’719 patent is illustrative and reproduced below (with
`added bracketing for reference):
`1. A solution of L-cysteine comprising,
`[A] a pharmaceutically acceptable carrier,
`[B] about 50 mg/mL of L-cysteine hydrochloride
`monohydrate, or equivalent amount of a pharmaceutically
`acceptable L-cysteine or a salt or hydrate thereof,
`[C] less than about 150 ppb of aluminum,
`[D] a pH from about 1.0 to about 2.5, and
`[E] wherein the solution is substantially free of visually
`detectable particulate matter and suitable for use as an additive
`in a parenteral nutrition composition for administration to an
`individual.
`Ex. 1106, 58:34–44 (emphasis added).
`E.
`Prior Art
`Petitioner relies upon the following prior art reference1 (Pet. 6):
`References
`Patent / Publication
`Exhibits
`Sandoz Label
`L-CYSTEINE HYDROCHLORIDE –
`Ex. 1005
`cysteine hydrochloride injection, solution
`Sandoz Inc.
`
`
`1 Petitioner additionally cites references in support of the knowledge of a
`person of ordinary skill in the art. See Pet. 30–35.
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`In addition, Petitioner relies on the affidavit of Christopher Butler of
`the Internet Archive (Ex. 1004) and its attached exhibits to establish the
`availability of the reference.
`F.
`Asserted Ground of Unpatentability
`Petitioner challenges the patentability of claims 1–27 of the ’719
`patent on the following ground (Pet. 6):
`Claim(s)
`Basis Reference(s)
`Challenged
`1–27
`
`§ 103 The Sandoz Label in view of the knowledge of
`a person of ordinary skill in the art
`Petitioner also relies on the Declarations of Barrett Rabinow, Ph.D.
`(Ex. 1003) and Harry “Warren” Johnson (Ex. 1022, Ex. 1116) to support its
`assertions. Patent Owner relies on the Declaration of Robert J. Kuhn,
`PharmD (Ex. 2001) in support of its Patent Owner Preliminary Response.
`II. DISCUSSION
`Petitioner contends that claims 1–27 would have been obvious over
`the combination of the Sandoz Label and the knowledge of a person of
`ordinary skill in the art. See Pet. 25–54; Pet. Reply 1–9. Patent Owner
`opposes. See Prelim. Resp. 18–63; Sur-reply 1–10. We begin by providing
`an overview of the prior art, followed by our analysis of the merits.
`A.
`Overview of Petitioner’s Reference
`“Sandoz Label” (Ex. 1005)
`The Sandoz Label2 describes a solution containing 50 mg of L-
`cysteine hydrochloride monohydrate and water, with the air replaced with
`
`
`2 Petitioner identifies “the Sandoz Label” as including the product, package
`insert, and package label. See Pet. 26–29, 43 (citing Ex. 1003 ¶ 109;
`Ex. 1022 ¶ 15). Patent Owner contends that Petitioner’s identified “label”
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`nitrogen, and the solution having a pH 1.0–2.5. Ex. 1005, 5. The Sandoz
`Label indicates that the solution is supplied in either 10 ml or 50 ml
`containers. Id. at 9. “L-Cysteine is a sulfur-containing amino acid. In
`premixed solutions of crystalline amino acids, cysteine is relatively unstable
`over time, eventually converting to insoluble cystine.” Id. at 1. The indicated
`use of L-cysteine hydrochloride injection as described in the Sandoz Label is
`for dilution as an additive to crystalline amino acid injections to meet the
`intravenous amino acid nutritional requirements of infants receiving total
`parenteral nutrition. Id. at 2. The label describes that “[a]ny unused portion
`of the vial must be discarded within 4 hours after initial entry.” Id. at 9.
`The label indicates that the product contains no more than 5000
`mcg/L [(5000 ppb)3] of aluminum. Id. at 5, 10 .The Sandoz Label provides a
`warning that the product contains aluminum that may be toxic. Id. at 2.
`“Research indicates that patients with impaired kidney function, including
`premature neonates, who receive parenteral levels of aluminum at greater
`than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with
`central nervous system and bone toxicity. Tissue loading may occur at even
`lower rates of administration.” Id. (emphasis omitted).
`B.
`Level of Ordinary Skill in the Art
`The level of skill in the art is a factual determination that provides a
`primary guarantee of objectivity in an obviousness analysis. Al-Site Corp. v.
`
`
`reaches three distinct sources of alleged prior art: the product itself, the
`package label, and the package insert (i.e., printed matter). Prelim. Resp. 29.
`Patent Owner contends that each source should be treated as separate prior
`art. Id. at 31. We address Patent Owner’s arguments below.
`3 5000 mcg/L corresponds to 5000 ppb. See Ex. 1003 ¶ 32; Ex. 2001 ¶ 20.
`
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`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)).
`Petitioner asserts that the ordinary skilled artisan “would have had a
`Ph.D. in chemistry or biochemistry and at least 2 years of work experience
`with pharmaceutical drug product formulation analysis, development,
`optimization, and manufacture.” Pet. 23–24 (citing Ex. 1003 ¶ 25).
`Patent Owner asserts that Petitioner’s definition of an ordinary skilled
`artisan misses the mark because it ignores the need for the artisan4 to also
`have “knowledge or experience in assessing whether a solution is suitable
`for administration in a clinical setting, in interpreting pharmaceutical drug
`labels, or consulting with someone who routinely does these things.” Prelim.
`Resp. 26 (citing Ex. 2001).
`We note that the descriptions asserted by Petitioner and Patent Owner
`suggest that the level of skill in the art is considerably high. Patent Owner’s
`description is more limiting than Petitioner’s description in that it requires
`the person of ordinary skill also have clinical knowledge that is pertinent to
`interpreting pharmaceutical drug labels. Prelim. Resp. 26. Patent Owner,
`however, does not propose its own alternative definition of a person of
`ordinary skill in the art, acknowledging instead that the Petition fails even
`under Petitioner’s construction. Id. at 27 (“the Board need not resolve the
`
`
`4 To the extent that Patent Owner challenges Petitioner’s expert, Dr.
`Rabinow, as lacking the foundation necessary to opine as a person of
`ordinary skill in the art in interpreting pharmaceutical drug labels, we
`address the weight to be given to his testimony in our obviousness analysis.
`Prelim Resp. 26, 41.
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`level of ordinary skill in the art in order to deny the Petition because, even
`under Eton’s definition, the Petition falls short.”).
`We find that the record as a whole supports Petitioner’s description of
`the level of ordinary skill in the art. For purposes of our analysis in this
`Decision, we hereby adopt Petitioner’s definition of a person of ordinary
`skill in the art. We also note that Petitioner’s proposed definition appears to
`be consistent with the cited prior art. See Okajima v. Bourdeau, 261 F.3d
`1350, 1355 (Fed. Cir. 2001).
`C.
`Claim Construction
`Petitioner proposes constructions for several claim terms: “about”
`“substantially free” and “essentially free.” See Pet. 24–25 (citing Ex. 1106 at
`17:61–18:5, 57:63–58:6). Patent Owner contends that there is no need to
`resolve any claim construction terms. Prelim Resp. 25.
`Because this decision declining to institute trial does not turn on the
`adoption of any particular claim construction, we need not construe any
`terms. See Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co. Matal,
`868 F.3d 1013, 1017 (Fed. Cir. 2017) (noting that “we need only construe
`terms ‘that are in controversy, and only 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)).
`D.
`Analysis
`The relevant statute provides that a determination whether to institute
`a post-grant review shall be made based on “the information presented in the
`petition.” 35 U.S.C. § 324(a). Under 35 U.S.C. § 324(a), a post-grant review
`can be instituted only if it is more likely than not that the petitioner would
`prevail with respect to at least one of the claims challenged in the petition.
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`Id. In addition, 35 U.S.C. § 322(a)(3) provides that the petition may be
`considered only if it identifies “in writing and with particularity, each claim
`challenged, the grounds on which the challenge to each claim is based, and
`the evidence that supports the grounds for the challenge to each claim.”
`Section § 42.22(a)(2) of Title 37 of the US Code of Federal Regulations
`provides that each petition must include, “[a] full statement of the reasons
`for the relief requested, including a detailed explanation of the significance
`of the evidence including material facts, and the governing law, rules, and
`precedent.” See also 37 C.F.R. § 42.204 (2020).
`In a post-grant review, as in an inter partes review, “the petitioner has
`the burden from the onset to show with particularity why the patent it
`challenges is unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d
`1356, 1363 (Fed. Cir. 2016) (emphasis added) (citing 35 U.S.C. §312(a)(3)
`as applied to inter partes review, which is equivalent to 35 U.S.C.
`§ 322(a)(3) as applied to post-grant review). This burden of persuasion never
`shifts to Patent Owner. See Dynamic Drinkware, LLC v. Nat’l Graphics,
`Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015); see also In re Magnum Oil Tools
`Int’l, Ltd., 829 F.3d 1364, 1375–78 (Fed. Cir. 2016) (discussing the burden
`of proof in AIA trials).
`1.) The Parties’ Contentions
`Petitioner contends that the challenged claims would have been
`obvious based on the Sandoz Label in conjunction with the knowledge of a
`person of ordinary skill in the art. Pet. 43–72. Petitioner provides a detailed
`analysis of how each claim element is allegedly described by the prior art.
`Id. Petitioner also relies on the declaration of Dr. Rabinow to support this
`challenge. See id.
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`We focus our analysis on representative claim 1 and particularly
`element 1(C)’s requirement of a range of aluminum as measured in ppb that
`is not taught by the asserted art. Because each challenged claim includes this
`or a similar requirement, it is dispositive of our conclusion to deny
`institution.
`Petitioner contends that claim elements 1(A), 1(B), 1(D) and 1(E) are
`disclosed in the Sandoz Label. Pet. 44–45. With respect to element 1(C),
`Petitioner contends that “[t]he Sandoz Label discloses a product that
`‘[c]ontains no more than 5,000 mcg/L [i.e., 5000 ppb] of aluminum,’ which
`encompasses the claimed range of ‘less than about 150 ppb of aluminum.’”
`Id. 42 (citing Ex. 1003 ¶ 109; Ex. 1005, 5, 10; Ex. 1004, 8, 13). Petitioner
`argues that there is nothing unexpected or surprising about the claimed range
`and that the claimed range is the expected result of optimizing the “Sandoz
`L-Cysteine Product in response to regulatory and market pressures.” Id. at
`43.
`
`In response, Patent Owner argues that the Petition does not provide
`“any explanation as to why a [person of ordinary skill in the art] would have
`had a reasonable expectation of success in solving the ‘decades old’
`aluminum problem through mere alleged ‘routine’ optimization.” Prelim
`Resp. 10. Patent Owner contends that the Petition lacks the particularity
`required by 35 U.S.C. §322(a). Specifically, Patent Owner contends that
`Eton relies on a “Sandoz product” manufactured by Allergy
`Labs, and refers to this product interchangeably with the
`Sandoz label and package insert at Exhibit 1005 (“Sandoz
`Label”). Eton never establishes that any product, let alone a
`product with characteristics beyond those described in the
`Sandoz Label, qualifies as prior art. Yet Eton relies on
`characteristics of a product made by Allergy Labs that were
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`either unknowable to the POSITA [(person of ordinary skill in
`the art)] (e.g., as-tested aluminum levels of the product before
`release to the public), or for which there is zero evidence in the
`record (e.g., as-tested aluminum levels of the product from 1-24
`months) beyond the say-so of an interested declarant with a
`huge financial interest in Eton succeeding in this PGR
`proceeding. Eton must be limited to the product characteristics
`described in the Sandoz Label, and that label makes clear the
`product may contain up to 5,000 ppb of aluminum during its
`shelf life.
`Prelim Resp. 11 (emphasis omitted) (footnote omitted). Patent Owner
`contends that “[t]he Petition repeatedly conflates a so-called ‘Sandoz
`product’ with the ‘Sandoz Label’ (i.e., the Sandoz package label and
`package insert, Ex. 1005), treating them as a single prior art source (Ex.
`1005) so as to back-door unproven product characteristics to try to show
`obviousness.” Id. at 29.
`Additionally, Patent Owner argues that nothing in the record suggests
`that Petitioner’s expert is “qualified to interpret labels for parenteral
`products that are intended for use by clinicians or that he has any experience
`in doing so.” Id. at 41. Patent Owner argues that Petitioner’s routine
`optimization argument is infected with hindsight assumptions and ignores
`the complexity of the environmental conditions that contribute to the
`aluminum levels in parenteral solutions. See id. at 44–56. Finally, Patent
`Owner argues that we should exercise our discretion and deny institution
`under 35 U.S.C. § 324(a).5 See id. at 64–66.
`
`
`5 We acknowledge Patent Owner’s position that we should deny institution
`under 35 U.S.C. § 324(a) because it would be inefficient and wasteful of the
`Board’s resources and that the same issues will be addressed in the co-
`pending district court litigation. Prelim. Resp. 12; see also Pet. Reply 9 (“If
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`In its Reply, Petitioner contends that the person of ordinary skill in the
`art would have been motivated to reduce aluminum levels in the Sandoz
`Label product by removing sources of aluminum contamination.
`Pet. Reply 2. Petitioner contends that Patent Owner does not cite any failed
`attempts in solving the aluminum problem. Id. at 3. Petitioner cites
`aluminum levels measured by Allergy Labs a producer of the Sandoz Label
`product to establish low levels of aluminum in the Sandoz product right after
`manufacture. Id. Petitioner contends that Patent Owner is introducing
`complexity in the manufacture of the product when the solution of
`minimizing or preventing aluminum contamination was simple and straight
`forward. Id. at 4. Petitioner contends that Patent Owner fails to establish the
`relatedness of aluminum contamination and particulate matter formation. Id.
`at 7.
`
`In its Sur-reply, Patent Owner argues that Petitioner has improperly
`presented new theories of unpatentability in Petitioner’s Reply. Specifically,
`Patent Owner contends that Petitioner now argues that a person of ordinary
`skill in the art “would have a reasonable expectation of success regardless of
`how the Sandoz label is interpreted.” Sur-reply 2. Patent Owner contends
`that “the Schott Type I Plus vial with the silicon dioxide lining was available
`at least as early as 2006. Yet, as of May 2019 Sandoz still had not solved the
`problem and instead sought to license Exela’s low-aluminum ELCYS®
`product within weeks of Exela’s NDA approval.” Id. at 4 (footnote omitted)
`
`
`the PO is truly interested in avoiding parallel proceedings and purportedly
`unnecessary litigation, it can join Petitioner’s motion and urge the district
`court to stay that action.”). Because we deny institution on the merits, we do
`not address the issues raised under 35 U.S.C. § 324(a).
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`(citing Ex. 1014, 2, 8; Prelim. Resp. 5–6). Patent Owner reiterates that Eton
`conflates the Sandoz Label and the “Sandoz product” in order to backfill
`information not found in the label. Id. at 7. Patent Owner contends that Eton
`has not established that “any particular product qualifies as prior art” or how
`a person of ordinary skill in the art would have had access to the product
`before its release. Id. at 8–9.
`We address the parties’ contentions below.
`2.) Particularity
`Petitioner relies on “[t]he Sandoz Label [as] disclos[ing] a product
`that ‘[c]ontains no more than 5,000 mcg/L [i.e., 5000 ppb] of aluminum,’
`which encompasses the claimed range of ‘less than about 150 ppb of
`aluminum.’” Pet. 42 (citing Ex. 1003 ¶ 109; Ex. 1005, 5, 10; Ex. 1004, 8,
`13); In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003) (“a prior art
`reference that discloses a range encompassing a somewhat narrower claimed
`range is sufficient to establish a prima facie case of obviousness”); see also
`ClearValue, Inc. v. Pearl River Polymers, Inc., 668 F.3d 1340, 1345 (Fed.
`Cir. 2012) (disclosure of “150 ppm or less” teaches “50 ppm”)), see also
`Pet. 38 (“As reported by the Sandoz Label, the Sandoz product contained
`aluminum in the range of 0 ppb to 5,000 ppb. Ex. 1003 ¶ 32; Ex. 1005, 5,
`10; Ex. 1004, 8, 13.”). Petitioner reasons that a person of ordinary skill in the
`art could have easily determined the aluminum levels in “the Sandoz product
`disclosed by the Sandoz Label by testing the product. The aluminum levels
`in the Sandoz product were typically less than 100 ppb shortly after
`manufacture and increased to several hundred ppbs during storage.” Pet. 43
`(citing Ex. 1003 ¶ 109; Ex. 1022 ¶ 15). In other words, Petitioner’s position
`is that if a person of ordinary skill in the art had tested the Sandoz product,
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`they would have determined that right after manufacture, the aluminum
`levels were at the low end of the alleged 0 to 5000 ppb range.
`Petitioner’s recited ground of unpatentability, however, relies solely
`on the Sandoz Label in view of the knowledge of a person of ordinary skill
`in the art. Based on that articulated ground, we agree with Patent Owner that
`the Petition suffers from a lack of particularity because the Petition
`“improperly mixes-and-matches two different types of alleged prior art
`under the ‘Sandoz Label’ umbrella—(1) the contents of a printed
`publication, and (2) alleged features of a ‘Sandoz product’ associated with
`that label that are neither described by the label nor substantiated with any
`evidence.” Prelim Resp. 27–28, see also id. at 29 (“The Petition repeatedly
`conflates a so-called ‘Sandoz product’ with the ‘Sandoz Label’ (i.e., the
`Sandoz package label and package insert, Ex. 1005), treating them as a
`single prior art source (Ex. 1005) so as to back-door unproven product
`characteristics to try to show obviousness.”); Sur-reply 7–9. Petitioner’s
`expert, Dr. Rabinow in his declaration similarly mixes-and-matches the two
`different types of prior art under the Sandoz Label. See Ex. 1002 ¶¶ 31–33,
`106–113 (citing Ex. 1022).
`“In an IPR, the petitioner has the burden from the onset to show with
`particularity why the patent it challenges is unpatentable.” Harmonic Inc. v.
`Avid Technology, Inc., 815 F.3d 1356, 1363 (2016). “Section 312(a)(3)’s
`particularity requirement is designed, at least in part, to ensure that a patent
`owner has sufficient notice of the challenge against which it must defend.”
`Cuozzo Speed Technologies, LLC v. Lee, 136 S.Ct. 2131, 2154 (2016)
`Section 312(a) relates to inter partes reviews (IPRs) and the similarly
`worded Section 322(a) relates to post-grant reviews (PGRs); we interpret
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`these two statutory sections similarly. Here, by mixing the two different
`types of art Petitioner is asking us read information into the Sandoz Label
`that is not there, and this does not satisfy the notice requirement under
`section 322(a). Accordingly, we agree with Patent Owner that the Petition
`lacks particularity.
`3.) Range
`We additionally find that Petitioner’s argument that a person of
`ordinary skill in the art would have understood the Sandoz Label to teach a
`range of 0 to 5,000 ppm aluminum is not supported by the evidence of
`record. The Sandoz Label (i.e., the package label and container labeling)
`states: “L-Cysteine Hydrochloride Injection, USP, 50 mg/ml, is a sterile,
`nonpyrogenic solution. Each ml contains: 50 mg of L-Cysteine
`Hydrochloride Monohydrate USP; Water for Injection, USP q.s.; Air
`replaced With Nitrogen. pH 1.0-2.5.” Ex. 1005, 1; see also id. at 5, 10. The
`Sandoz Label describes that the product “L-Cysteine Hydrochloride
`Injection, USP is intended for use only after dilution as an additive to
`Crystalline Amino Acid Injections to meet the intravenous amino acid
`nutritional requirements of infants receiving total parenteral nutrition.” Id.
`at 2. The Sandoz Label explains that the product contains aluminum. Id.
`((“WARNING: This product contains aluminum that may be toxic.”
`(emphasis omitted)); see Ex. 1003 ¶ 32; Ex. 2001 ¶ 19). The Sandoz Label
`states that the product contains “no more than 5,000 mcg/L aluminum”
`(corresponding to 5000 ppb). Ex. 1005, 5, 10; see Ex. 1003 ¶ 32; Ex. 2001
`¶ 21.
`
`Patent Owner contends nothing in the record suggests that Petitioner’s
`expert, Dr. Rabinow, is “qualified to interpret labels for parenteral products
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`that are intended for use by clinicians or that he has any experience in doing
`so.” Prelim Resp. 41. Patent Owner argues that clinical knowledge is
`pertinent to interpreting pharmaceutical labels such as the Sandoz Label. Id.
`at 26 (citing Ex. 2001). Patent Owner challenges Petitioner’s expert
`conclusion that one of ordinary skill in the art would interpret the Sandoz
`Label as reciting a range of 0 to 5000 ppb. Prelim Resp. 40 (citing See
`Innovations4Flooring NV v. Valinge Innovation AB, IPR2017-02130, Paper
`36, 57–58 (PTAB Mar. 25, 2019) (assigning “limited weight” to expert’s
`testimony where expert did not possess the “practical experience” that a
`person of ordinary skill in the art would have possessed)).
`Petitioner’s expert, Dr. Rabinow recognizes that the Sandoz Label
`warns that “this product contains aluminum that may be toxic.” Ex. 1003
`¶ 32. Dr. Rainbow never the less avers that the recitation “[c]ontains no
`more than 5,000 mcg/L [i.e., 5,000 ppb] of aluminum” in the Sandoz Label
`would have been understood by a person of ordinary skill in the art “to mean
`aluminum in an amount falling somewhere within the range of 0 ppb to
`5,000 ppb.” Id. As explained in our trial practice guide, the relative weight
`that we assign expert testimony is subject to various factors. See,
`e.g., Consolidated Trial Practice Guide6 40 (“Opinions expressed without
`disclosing the underlying facts or data may be given little or no weight.”). In
`this case, we find that a recognition in the Sandoz Label that the product
`contains aluminum reasonably undercuts a conclusion that the lower limit of
`
`
`6 A copy of the Trial Practice Guide is available at:
`https://www.uspto.gov/TrialPracticeGuideConsolidated
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`the Sandoz Label is zero. (Ex. 1005, 8 (“WARNING: This product contains
`aluminum that may be toxic” (emphasis omitted)).
`Patent Owner’s expert, Dr. Kuhn avers that a pharmacist reading the
`label would interpret “[c]ontains no more than 5,000 mcg/L [i.e., 5,000 ppb]
`of aluminum” as being the maximum aluminum content. Ex. 2001 ¶ 15 (“In
`2004, the Food and Drug Administration . . . issued a rule requiring that
`additives used to compound TPN [(total parenteral nutrition)] have the
`maximum aluminum content at expiration listed on the product label.”); Ex.
`1007, 1 (“Manufacturers currently label these products with the maximum
`aluminum content at the time of expiry.”). Dr. Kuhn further explains that
`when
`calculating the potential aluminum exposure for a patient
`receiving TPN solution that uses the Cysteine HCl Product [, a
`pharmacist] would use the 5,000 mcg/L aluminum
`concentration to do so. The package label expressly teaches the
`product could contain up to 5,000 mcg/L of aluminum, and any
`prudent pharmacist would use that maximum aluminum level to
`calculate potential aluminum exposure so as to not
`underestimate the content of the potential for aluminum
`toxicity.
`Ex. 2001 ¶ 21.
`The evidence in the record (see Ex. 1007, 2) supports Dr. Kuhn’s
`position that the Sandoz Label recites th
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