Trials@uspto.gov Paper No. 14
`571-272-7822
`
` Date: December 21, 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.
`____________
`
`PGR2020-00064
`Patent 10,478,453 B1
`____________
`
`
`
`Before ULRIKE W. JENKS, SUSAN L. C. MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Petitioner’s Request on Rehearing of Decision Denying Institution
`of Post-Grant Review
`37 C.F.R. § 42.71(d)
`
`
`
`
`
`
`
`571-272-7822
`
` Date: December 21, 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.
`____________
`
`PGR2020-00064
`Patent 10,478,453 B1
`____________
`
`
`
`Before ULRIKE W. JENKS, SUSAN L. C. MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Petitioner’s Request on Rehearing of Decision Denying Institution
`of Post-Grant Review
`37 C.F.R. § 42.71(d)
`
`
`
`
`
`
`
`
`PGR2020-00064
`Patent 10,478,453 B1
`
`I. INTRODUCTION
`Eton Pharmaceuticals Inc. (“Petitioner”) requests rehearing of our
`Institution Decision (“Decision”) denying post-grant review of claims 1–22
`of U.S. Patent No. 10,478,453 B1 (Ex. 1001, “the ’453 patent”) entered on
`November 18, 2020 (Paper 12, “Dec.”). Paper 13 (“Req. Reh’g”).
`We denied institution based on our determination that Petitioner’s
`contentions relying on reasonable expectation of success based on
`overlapping ranges was not sufficiently supported by the evidence in the
`record. Dec. 12–22. We also determined that the Petition fails to meet the
`particularity requirement of 35 U.S.C. § 322(a)(3) with regard to Petitioner’s
`assertion that the subject matter of the claims would have been obvious over
`the Sandoz Label in conjunction with the knowledge of a person of ordinary
`skill in the art. Dec. 17.
`In its Request for Rehearing, Petitioner contends that the Board in the
`Decision misapprehends Petitioner’s assertions that do not rely on
`overlapping ranges to establish unpatentability, and that the Board abused its
`discretion in finding lack of particularity. See generally Req. Reh’g.
`Having reconsidered Petitioner’s arguments in view of the Request for
`Rehearing, we modify the Decision to incorporate and address Petitioner’s
`contentions with respect to their reasonable expectation of success
`assertions. For the reasons discussed below, the modification of our
`Decision does not alter the outcome. As a result, we deny Petitioner’s
`Request for Rehearing.
`STANDARD OF REVIEW
`II.
`A party requesting rehearing has the burden to show a decision should
`be modified by specifically identifying all matters the party believes were
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`misapprehended or overlooked, and the place where each matter was
`addressed previously in a motion, opposition, or a reply. 37 C.F.R.
`§ 42.71(d). When rehearing a decision on institution, we review the decision
`for an abuse of discretion. 37 C.F.R. § 42.71(c). An abuse of discretion may
`arise if a decision is based on an erroneous interpretation of law, if a factual
`finding is not supported by substantial evidence, or if the decision represents
`an unreasonable judgment in weighing relevant factors. Star Fruits S.N.C. v.
`United States, 393 F.3d 1277, 1281 (Fed. Cir. 2005); Arnold P’ship v.
`Dudas, 362 F.3d 1338, 1340 (Fed. Cir. 2004); In re Gartside, 203 F.3d
`1305, 1315–16 (Fed. Cir. 2000).
`III. ANALYSIS
`In its Request for Rehearing, Petitioner contends that the Board in the
`Decision misapprehends Petitioner’s reasonable expectation of success
`assertions, and abused its discretion in finding lack of particularity in the
`Petition. See generally Req. Reh’g.
`1.) Reasonable Expectation of Success
`In the Decision, we determined that the product described by the
`Sandoz Label does not disclose a range for aluminum from 0 to 5,000 ppb.
`Dec. 22. Therefore, we were not persuaded “by Petitioner’s position that
`there is a reasonable expectation that routine optimization would lead to
`aluminum concentrations as recited in claim 1 of the ’453 patent based on
`optimizing overlapping ranges.” Id.
`Petitioner argues that in the Petition it presented a separate reasonable
`expectation of success argument that is based on routine optimization, which
`does “not depend exclusively on or require overlapping ranges.” Req. Reh’g
`5; see, e.g., Pet. 45 (“[T]he claimed range is the expected result of
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`Patent 10,478,453 B1
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`optimizing the Sandoz product in response to regulatory and market
`pressures to substantially reduce and eliminate aluminum from parenteral
`drug products.”).
`Even if we were to agree with Petitioner that the Petition included a
`separate “reasonable expectation of success argument” that did not rely on
`overlapping ranges, we again find that Patent Owner has the better position.
`In our Decision, we agreed with Petitioner that there was ample motivation
`for reducing aluminum levels in parenteral solutions. See Dec. 18. In the
`Decision, however, we explained that motivation alone is not sufficient for
`reaching a conclusion of obviousness because it does not, without more,
`provide a path for how to achieve the stated goal. Id.
`Petitioner contends that the claimed aluminum levels were not new,
`and that a person of ordinary skill in the art would have had a reasonable
`expectation that the Sandoz Label product could be optimized to
`substantially eliminate aluminum. See Req. Reh’g 1–2. Petitioner contends
`that the Decision overlooks that a person of ordinary skill in the art would
`have eliminated “known sources of aluminum” (Req. Reh’g 3), for example,
`by packaging the Sandoz Label product into “Schott coated glass vials” to
`arrive at the claimed invention (id. (citing Pet. 38–39, 40–43, 46)). Petitioner
`contends that the Decision overlooks the dispositive impact of the
`knowledge one of ordinary skill in the art would have possessed about
`Schott coated glass vials in order to prevent aluminum leaching of the
`Sandoz product if packaged into such a vial. See id. at 4, n.6.
`The issue is not whether an ordinary artisan would have recognized
`sources of aluminum contamination that could potentially be eliminated; the
`question is whether there would have been a reasonable expectation that
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`PGR2020-00064
`Patent 10,478,453 B1
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`removing an aluminum source would result in a stable product as defined by
`the ’453 patent. We agree with Patent Owner’s response that “the kinetics
`and equilibrium chemistry of the various L-cysteine and L-cystine species in
`any particular L-cysteine solution are complex and influenced by multiple
`interacting variables of that environment, including oxygen levels, pH, and
`the presence of trace metals.” Prelim Resp. 14–15. Patent Owner further
`explains “that ‘removing Aluminum may have the unintended consequence
`of increased [L-cystine] precipitation and product failure in the presence of
`even small amounts of oxygen in the container.’” Id. at 16 (alteration in
`original) (quoting Ex. 1001, 5:4–9 (“[R]emoving Aluminum may have the
`unintended consequence of increased precipitation and product failure in the
`presence of even small amounts of oxygen in the container. This was
`unexpected.”)). In other words, the removal of aluminum has the unintended
`consequence of making the product more susceptible to oxygen, resulting in
`product precipitation, and thereby rendering the product unsuitable for
`parenteral administration. Id. at 44 (“[O]nly in hindsight was the L-cysteine
`aluminum problem a ‘puzzle,’ i.e., a multifaceted problem with many
`interrelated pieces to be solved.”).
`Petitioner contends that the Decision “suffers from two fundamental
`misapprehensions of the record. First, it conflates the Sandoz product with
`the Sandoz Label. . . . Second, not only do the aluminum levels in the
`Sandoz product manufactured by Allergy Labs overlap with the claimed
`aluminum ranges, but also they corroborate the reasonableness of
`Dr. Rabinow’s interpretation of the Sandoz Label.” Req. Reh’g 7–8; see id.
`at 5 (arguing that the Decision “overlooks the unrebutted evidence that
`demonstrates that the ranges do in fact overlap”).
`
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`Patent 10,478,453 B1
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`We are not persuaded by Petitioner’s contention that the Decision
`conflates the Sandoz Label with the Sandoz Product. Indeed, as we noted in
`the Decision, the Petition mixes information from these two distinct sources.
`See Dec. 7 n.3; Pet. 1 (identifying “the prior art Sandoz L-Cysteine
`Hydrochloride Injection (50 mg/mL) product, package insert and package
`label (‘Sandoz Label’)” (emphasis added)). When describing the product
`associated with the Sandoz Label, the Petition repeatedly references
`information that is not part of the label – but instead suggests that a person
`of ordinary in in the art could have measured certain aluminum levels in the
`Sandoz Product. Id. at 41 (suggesting that a person of ordinary skill could
`have determined aluminum levels in the Sandoz Product and if they did so,
`would have found that the product contained less than 100 ppb (citing Ex.
`1022 ¶ 15; Ex. 1003 ¶¶ 33, 98, 119, 122, 125, 128, 131, 142, 162, 180,
`210)), 45 (aluminum levels in the Sandoz Product typically less than 100
`ppb (citing Ex. 1003 ¶ 98; Ex. 1022 ¶ 15)).
`We are not persuaded by Petitioner’s contention that the aluminum
`levels in the Sandoz product manufactured by Allergy Labs overlap with the
`claimed aluminum ranges. Specifically, Petitioner contends that it provided
`unrebutted expert testimony supporting its position. Req. Reh’g 4. Petitioner
`contends that we should accept the unrebutted testimony that a person of
`ordinary skill in the art would have interpreted the Sandoz Label as
`disclosing an aluminum concertation “‘falling somewhere within the range
`of 0 ppb to 5,000 ppb’ (i.e., 5,000 ppb aluminum or less) and that the claim 1
`range of from about 1-250 ppb aluminum is within the lower end of the not
`more than 5,000 ppb range.” Req. Reh’g. 7.
`
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`“The Board has broad discretion to assign weight to be accorded
`expert testimony.” Consolidated Trial Practice Guide1 (“CTPG”) 35 (Nov.
`2019); see id. at 40–41 (“Opinions expressed without disclosing the
`underlying facts or data may be given little or no weight. Rohm & Haas Co.
`v. Brotech Corp., 127 F.3d 1089, 1092 (Fed. Cir. 1997) (nothing in the
`Federal Rules of Evidence or Federal Circuit jurisprudence requires the fact
`finder to credit unsupported assertions of an expert witness)”). In this case,
`Petitioner has not directed us to corroborating evidence to suggest that zero
`is a reasonable lower limit based on the disclosure in the Sandoz Label. To
`the contrary, Petitioner directs us to evidence in the record (see Pet. 41
`(citing Ex. 1022 ¶ 15 (citing Exhibit B and C))) that supports the warning in
`the Sandoz Label that the product contains aluminum, establishing that the
`lower limit is not reasonably zero. See Dec. 8 (citing Ex. 1005, 2). In the
`Decision, we credited Dr. Kuhn’s testimony, which is supported by the
`record, and determined that “the evidence supports the position that the
`Sandoz product label recites the contamination level at the expiration date.”
`Dec. 20 (citing Ex. 2001 ¶ 22; Ex. 1007, 1). Based on these disclosures in
`the Sandoz Label, we concluded that the evidence in the record does not
`support Petitioner’s position that “the Sandoz Label should be interpreted as
`a disclosure of an aluminum range from 0 to 5000 ppb,” an interpretation
`relied on in Petitioner’s articulated grounds of unpatentability. See Dec. 19.
`Accordingly, we are not persuaded by Petitioner’s contention that we abused
`our discretion in concluding that the disclosure of the Sandoz Label does not
`
`
`1 Available at https://www.uspto.gov/TrialPracticeGuideConsolidated.
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`overlap with or encompass the 1–250 ppb aluminum range recited in claim 1
`of the ’453 patent.
`We further evaluate Petitioner’s expert testimony against the backdrop
`that it took more than a decade to develop a cysteine containing parenteral
`composition that met the established FDA requirements. Considering the
`great pressure given by the FDA recommendation to lower aluminum
`content in parenteral solutions to avoid aluminum toxicity and the length of
`time it took the industry to produce such a product, we find that, on balance,
`this suggests that the solution to the problem was not straightforward as
`urged by Petitioner. See Prelim Resp. 10, 14–17, 44 (citing Leo Pharm.
`Prods., Ltd. v. Rea, 726 F.3d 1346, 1354 (Fed. Cir. 2013) (“If these
`discoveries and advances were routine and relatively easy, the record would
`undoubtedly have shown that some ordinary artisan would have achieved
`this invention within months of [the prior art patents]. Instead this invention
`does not appear for more than a decade.”)). Specifically, we agree with
`Patent Owner’s assertion 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. Prelim. Resp. 43–44. Here, the person of ordinary skill
`in the art would have been highly motivated to solve the “alleged ‘problem
`of aluminum’” and yet the problem had “gone unsolved for more than a
`decade” despite the supposedly “simple and straightforward solutions.” Id. at
`44 (citing Leo Pharm. Prods., 726 F.3d at 1354). Given this backdrop, we
`agree with Patent Owner’s assertion that Petitioner has not articulated why a
`person of ordinary skill in the art would have had a “reasonable expectation
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`of success in solving the decades old aluminum problem.” Id. at 7 (citation
`and quotation omitted).
`In summary, in the Decision we agreed with Petitioner that there was
`ample motivation to lower aluminum concentration in parenteral
`compositions. Motivation alone, however, is not sufficient for reaching a
`conclusion of obviousness. See Dec. 18. At best, the Petition and supporting
`Rabinow Declaration identify aluminum contributing sources in the Sandoz
`Label product that one of ordinary skill in the art would have known about
`and that could have been substituted by trial and error. Considering the
`incentive given by the FDA recommendation to lower aluminum content in
`parenteral solution in order to avoid aluminum toxicity when balanced
`against the length of time it took the industry to produce such a product, we
`find that extended time between these events sufficiently suggests that the
`solution to the problem was not as straightforward or routine as urged by
`Petitioner. See Leo Pharm. Prods., 726 F.3d at 1354.
`2.) Particularity
`We are not persuaded by Petitioner’s contention that “the Board
`abused its discretion in finding a lack of particularity.” Req. Reh’g 8.
`Petitioner contends that the Decision misapprehends the asserted grounds
`and conflates references that merely corroborate the knowledge of the
`person of ordinary skill in the art. See id. at 9. We agree with Patent Owner
`that the Petition is using the references as more than just corroborating prior
`art. Prelim. Resp. 29–31. Specifically, when describing the product
`associated with the Sandoz Label the Petition repeatedly references
`information that is not part of the label – but instead suggests that a person
`of ordinary in in the art could have measured certain aluminum levels in the
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`Sandoz Product. See Pet. 45 (suggesting that a person of ordinary skill could
`have determined aluminum levels in the Sandoz Product and if they did so
`would find that the product contained less than 100 ppb (citing Ex. 1022
`¶ 15; Ex. 1003 ¶ 33)). We understand that it is permissible to rely on expert
`evidence that is corroborated by prior art to be within the general knowledge
`of the skilled artisan. Koninklijke Philips N.V. v. Google LLC, 948 F.3d 1330
`(Fed. Cir. 2020). The information about specific product attributes, however,
`goes beyond the general knowledge of the ordinary artisan. Petitioner has
`not cited authority to establish that the general knowledge of the person of
`ordinary skill in the art includes the attributes of the Sandoz L-cysteine
`product that was sold in association with the Sandoz label. Accordingly, we
`are not persuaded that we abused our discretion in determining that the
`Petition lacked particularity under of 35 U.S.C. § 322(a)(3).
`3.) Evidence
`We are not persuaded by Petitioner’s contention that the Decision
`overlooks evidence that “[m]inimizing L-cystine is the reasonably expected
`result of preventing oxidative degradation of L-cysteine.” Req. Reh’g 13.
`Specifically, in the Decision, we agreed with Patent Owner that “Petitioner
`has not demonstrated that the oxidative behavior of L-cysteine in the pH
`range of 1.0–2.5 as listed on the Sandoz Label converts the L-cysteine to the
`unwanted cystine.” Dec. 16 (citing Prelim. Resp. 47 (citing Ex. 1020, 3 (“In
`neutral or slightly alkaline aqueous solutions, [cysteine hydrochloride] is
`oxidized to cystine by air. It is more stable in acidic solutions.”))). The
`Decision, therefore, recognizes that at the low pH recited in the Sandoz
`Label, the cysteine hydrochloride oxidation to the unwanted cystine occurs
`at a slow rate because it was known that cysteine hydrochloride is more
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`stable at low pH. In other words, we found that the Petition did not
`sufficiently articulate why “optimizing the cystine levels in a composition
`that has the recited low pH” is something that one of ordinary skill in the art
`would have considered necessary, since it was known that cysteine
`hydrochloride is more stable at low pH. See Dec. 16–17, see also id. at 17
`(“[T]he Petition does not sufficiently explain[] why one of ordinary skill in
`the art would want to look at cystine levels in the product disclosed in the
`Sandoz Label in the first place and what reason there is to maintain it within
`the recited range.”). Accordingly, we are not persuaded that we
`misapprehend or overlooked any evidence.
`IV. CONCLUSION
`We have reconsidered our decision of November 18, 2020, in light of
`
`Petitioner’s arguments in the Request for Rehearing, and we modify our
`Decision in response to Petitioner’s argument by incorporating our analysis
`herein with respect to the “reasonable expectation of success” (see above
`III.1) argument that Petitioner asserts does not rely on overlapping ranges.
`For the foregoing reasons, Petitioner has not demonstrated that we abused
`our discretion in exercising our discretion to deny institution.
`V. ORDER
`In consideration of the foregoing, it is hereby ordered that Petitioner’s
`
`Rehearing Request is denied.
`
`
`11
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`PGR2020-00064
`Patent 10,478,453 B1
`
`PETITIONER:
`Ralph J. Gabric
`Eugene Goryunov
`Judy K. He
`HAYNES AND BOONE LLP
`ralph.gabric.ipr@haynesboone.com
`eugene.goryunov.ipr@haynesboone.com
`judy.he.ipr@haynesboone.com
`
`PATENT OWNER:
`Dorothy P. Whelan
`Alana Mannige
`FISH & RICHARDSON P.C.
`whelan@fr.com
`mannige@fr.com
`
`
`12
`
`
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