Case 1:15-cv-00697-RGA Document 133-1 Filed 02/04/20 Page 1 of 18 PageID #: 2937
`Case 1:15-cv-00697-RGA Document 133-1 Filed 02/04/20 Page 1 of 18 PageID #: 2937
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`EXHIBIT A
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`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`HOSPIRA, INC.,
`Plaintiff-Appellant
`
`v.
`
`FRESENIUS KABI USA, LLC,
`Defendant-Appellee
`______________________
`
`2019-1329, 2019-1367
`______________________
`
`Appeals from the United States District Court for the
`Northern District of Illinois in Nos. 1:16-cv-00651, 1:17-cv-
`07903, Judge Rebecca R. Pallmeyer.
`______________________
`
`Decided: January 9, 2020
`______________________
`
`ADAM G. UNIKOWSKY, Jenner & Block LLP, Washing-
`ton, DC, argued for plaintiff-appellant. Also represented
`by BRADFORD PETER LYERLA, AARON A. BARLOW, YUSUF
`ESAT, REN-HOW HARN, SARA TONNIES HORTON, Chicago, IL.
`
` IMRON T. ALY, Schiff Hardin LLP, Chicago, IL, argued
`for defendant-appellee.
` Also represented by KEVIN
`MICHAEL NELSON, JOEL M. WALLACE; AHMED M.T. RIAZ,
`New York, NY.
` ______________________
`
`Before LOURIE, DYK, and MOORE, Circuit Judges.
`
`

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`HOSPIRA, INC. v. FRESENIUS KABI USA, LLC
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`LOURIE, Circuit Judge.
`Hospira Inc. (“Hospira”) appeals from the judgment of
`the United States District Court for the Northern District
`of Illinois that claim 6 of U.S. Patent 8,648,106 (“the ’106
`patent”) is invalid as obvious. Hospira, Inc. v. Fresenius
`Kabi USA, LLC, 343 F. Supp. 3d 823 (N.D. Ill. 2018)
`(“Opinion”). Because we find that the district court’s fac-
`tual findings were not clearly erroneous and that those
`findings support a conclusion of obviousness, we affirm.
`BACKGROUND
`Hospira makes and sells dexmedetomidine products
`under the brand name Precedex, including a ready-to-use
`product known as Precedex Premix. Hospira owns a num-
`ber of patents that cover its Precedex Premix product.
`Fresenius Kabi USA LLC (“Fresenius”) filed an Abbrevi-
`ated New Drug Application (“ANDA”) seeking approval to
`enter the market with a generic ready-to-use dexme-
`detomidine product. Hospira sued for infringement of five
`patents and eventually dropped all but two claims, one of
`which was claim 6 of the ’106 patent.1 Fresenius stipulated
`to infringement of claim 6, and the district court held a
`bench trial on its validity.
`I. Prior Art Dexmedetomidine
`Dexmedetomidine is a chemical compound that is effec-
`tive as a sedative. ’106 patent col. 1 ll. 36–37. Dexme-
`detomidine was first developed and patented by Farmos
`Yhtyma Oy (“Farmos”) in the 1980s. Farmos was issued
`U.S. Patent 4,910,214, which disclosed the dexmedetomi-
`dine compound and its use as a sedative.
`
`
`1 The other asserted claim was claim 8 of U.S. Patent
`9,616,049, which the district court held would have been
`obvious and is not at issue in this appeal.
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`In 1989, Farmos submitted an Investigational New
`Drug application (“the Farmos IND”) to the U.S. Food and
`Drug Administration (“FDA”) seeking approval to begin
`safety testing dexmedetomidine formulations in humans.
`Farmos conducted at least two human safety studies using
`intravenous administration of 20 µg/mL dexmedetomidine
`hydrochloride but subsequently abandoned its safety test-
`ing after the studies showed adverse effects.
`In 1994, Farmos’s successor granted Abbott Laborato-
`ries (Hospira’s predecessor-in-interest) an exclusive license
`to make, use, and sell dexmedetomidine for human use in
`the United States. In 1999, Abbott Laboratories received
`FDA approval to market a 100 µg/mL dexmedetomidine hy-
`drochloride formulation known as “Precedex Concentrate.”
`Precedex Concentrate is supplied in 2 mL clear glass vials
`and 2 mL clear glass ampoules made from Type IA sulfur-
`treated glass sealed with coated rubber stoppers. The
`100 µg/mL concentration of Precedex Concentrate is too
`strong to be directly administered to patients, and thus the
`label provides instructions for diluting the drug to a con-
`centration of 4 µg/mL before intravenous administration.
`Dexmedetomidine is also available as a sedative for
`commercial veterinary use. In 2002, the European Medi-
`cines Evaluation Agency authorized use of a product called
`Dexdomitor, which is a ready-to-use 500 µg/mL formula-
`tion of dexmedetomidine hydrochloride. Dexdomitor is
`stored in a 10 mL glass vial sealed with a coated rubber
`stopper and has a two-year shelf life.
`II. The ’106 Patent
`The ’106 patent is entitled “Dexmedetomidine Premix
`Formulation” and is directed to pharmaceutical composi-
`tions comprising dexmedetomidine (or a pharmaceutically
`acceptable salt of dexmedetomidine) formulated as a liquid
`for parenteral administration to a patient, “wherein the
`composition is disposed within a sealed container as a pre-
`mixture.” ’106 patent at Abstract; see also ’106 patent col.
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`HOSPIRA, INC. v. FRESENIUS KABI USA, LLC
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`1 ll. 19–20 (“The present invention relates to patient-ready,
`premixed formulations of dexmedetomidine, or a pharma-
`ceutically acceptable salt thereof . . . .”). The ’106 patent
`describes the alleged problems associated with prior art
`dexmedetomidine formulations that the patented inven-
`tion was intended to solve:
`To date, dexmedetomidine has been provided as a
`concentrate that must be diluted prior to admin-
`istration to a patient. The requirement of a dilu-
`tion
`step
`in
`the
`preparation
`of
`the
`dexmedetomidine formulation is associated with
`additional costs and inconvenience, as well as the
`risk of possible contamination or overdose due to
`human error. Thus, a dexmedetomidine formula-
`tion that avoids the expense, inconvenience, delay
`and risk of contamination or overdose would pro-
`vide significant advantages over currently availa-
`ble concentrated formulations.
`Id. col. 1 l. 61–col. 2 l. 3.
`To address the perceived shortcomings of the prior art,
`the ’106 patent states that its invention relates to “pre-
`mixed pharmaceutical compositions of dexmedetomidine,
`or a pharmaceutically acceptable salt thereof, that are for-
`mulated for administration to a patient, without the need
`to reconstitute or dilute the composition prior to admin-
`istration.” Id. col. 2 ll. 7–11. The patent specifies that the
`invention can be formulated as a “ready to use” composi-
`tion, which is a premixed dexmedetomidine composition
`that is “suitable for administration to a patient without di-
`lution.” Id. col. 3 l. 66–col. 4 l. 2.
`Importantly, the ’106 patent states that “[t]he present
`invention is based in part on the discovery that dexme-
`detomidine prepared in a premixed formulation that does
`not require reconstitution or dilution prior to administra-
`tion to a patient, remains stable and active after prolonged
`storage.” Id. col. 3 ll. 6–10 (emphasis added). The patent
`
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`describes “stability studies” that were conducted to meas-
`ure the loss in potency of the drug over time. Id. col. 13–
`col. 25 (Examples 1, 2, 4, and 6, which describe studies of
`dexmedetomidine potency over time under different condi-
`tions). For instance, Example 1 describes a study of po-
`tency of a 4 µg/mL dexmedetomidine hydrochloride
`formulation over time when stored in different storage con-
`tainers, and Example 4 describes testing under different
`stresses and concludes that “[u]nder oxidative conditions,
`the sample showed highest amount of degradation.” Id. col.
`17 ll. 25–26.
`In Example 5, the patent describes a process by which
`a 4 µg/mL dexmedetomidine hydrochloride formulation
`“can be manufactured.” Id. col. 17 ll. 57–58. That example
`manufacturing process
`includes
`“[n]itrogen
`sparg-
`ing . . . throughout the manufacturing process.” Id. col. 17
`ll. 60–62. At the conclusion of the process, “[a]n atmos-
`phere of filtered nitrogen gas is maintained in the head-
`space of the surge bottle,” and “the headspace of the
`container is gassed with nitrogen to achieve not more than
`5% of oxygen in the headspace.” Id. col. 18 ll. 58–62.
`Claim 1 is the only independent claim in the ’106 pa-
`tent:
`1. A ready to use liquid pharmaceutical composi-
`tion for parenteral administration to a subject,
`comprising dexmedetomidine or a pharmaceuti-
`cally acceptable salt thereof disposed within a
`sealed glass container, wherein the liquid pharma-
`ceutical composition when stored in the glass con-
`tainer for at least five months exhibits no more
`than about 2% decrease in the concentration of dex-
`medetomidine.
`Id. col. 26 ll. 18–24. Claim 6, which depends from
`claim 1, is the only claim at issue in this appeal:
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`HOSPIRA, INC. v. FRESENIUS KABI USA, LLC
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`6. The ready to use liquid pharmaceutical composi-
`tion of claim 1, wherein the dexmedetomidine or
`pharmaceutically acceptable salt thereof is at a
`concentration of about 4 µg/mL.
`Id. col. 26 ll. 41–43.
`III. District Court Proceedings
`The district court held a five-day bench trial on Frese-
`nius’s defense that claim 6 of the ’106 patent is invalid as
`obvious over the prior art combinations of Precedex Con-
`centrate in combination with the knowledge of a person of
`ordinary skill in the art and Precedex Concentrate in com-
`bination with Dexdomitor. After the parties submitted
`their post-trial briefs, the court issued its findings of fact
`and conclusions of law, holding that Fresenius had proven
`by clear and convincing evidence that claim 6 would have
`been obvious over the prior art.
`The district court determined that “to prove that a
`claim covering multiple alternative embodiments is inva-
`lid, a defendant need only prove that one of the embodi-
`ments is invalid.” Opinion, 343 F. Supp. 3d at 845–46
`(citing In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1281
`(Fed. Cir. 2015)). Thus, the court focused on one allegedly
`obvious embodiment of claim 6, namely, “a ready-to-use,
`sealed glass container—made from Type I glass and a
`coated rubber stopper—with 4 µg/mL dexmedetomidine
`HCl,” which the court referred to as the “4 µg/mL preferred
`embodiment.”2 The court found that the 4 µg/mL preferred
`embodiment was expressly taught by the prior art, and the
`
`
`2 For consistency, we will similarly refer to this em-
`bodiment as the “4 µg/mL preferred embodiment” herein.
`
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`only dispute between the parties concerned the “about 2%”
`limitation in claim 6.3 Id. at 846.
`Based on the evidence in the trial record, the district
`court found that Fresenius had proven the following facts
`by clear and convincing evidence:
`All stability data in the record for 4 µg/mL dexme-
`detomidine HCl formulations stored in Type I glass
`vials, sealed with coated rubber stoppers, and
`stored at room temperature shows that there was
`“no more than about 2%” loss in concentration at
`five months.
`The “about 2%” limitation of the ’106 Patent is in-
`herent in a 4 µg/mL dexmedetomidine HCl formu-
`lation, stored in a Type I glass vial sealed with a
`coated rubber stopper, and stored at room temper-
`ature for five months.
`Opinion, 343 F. Supp. 3d at 841. To reach those findings,
`the district court relied on fact and expert testimony re-
`garding the stability data for more than 20 tested samples
`of 4 µg/mL dexmedetomidine hydrochloride in the record,4
`all of which met the about 2% limitation. Id. at 846-47.
`The court also relied on the conclusion of Fresenius’s expert
`that the concentration of dexmedetomidine does not have
`an effect on its stability. The court rejected Hospira’s
`
`3 The “about 2%” limitation refers to the claim limi-
`tation that reads “wherein the liquid pharmaceutical com-
`position when stored in the glass container for at least five
`months exhibits no more than about 2% decrease in the
`concentration of dexmedetomidine.”
`4 The samples included 18 batch configurations in
`the Precedex Premix New Drug Application (three vial
`sizes, each of which was analyzed in three upright and
`three inverted configurations) and three samples in Frese-
`nius’s ANDA. Opinion, 343 F. Supp. 3d at 833, 836.
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`HOSPIRA, INC. v. FRESENIUS KABI USA, LLC
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`arguments regarding stability data from 20 µg/mL samples
`in the Farmos IND, finding that Fresenius’s expert’s anal-
`ysis of that data was more reliable than that of Hospira’s
`expert. Id. at 849–50. Furthermore, the court noted that,
`although a district judge in Delaware had previously found
`(in a separate litigation brought by Hospira against a dif-
`ferent defendant) that the about 2% limitation had not
`been proven to be inherent, that decision was based on a
`different record and was not binding in this case. Id. at
`850–51 (citing Hospira, Inc. v. Amneal Pharm. LLC, 285 F.
`Supp. 3d. 776, 800 (D. Del. 2018), aff’d, 748 F. App’x 1024
`(Fed. Cir. 2019)).
`The district court then considered whether a person of
`ordinary skill would have had a reasonable expectation of
`success in achieving the about 2% limitation from combin-
`ing the other limitations disclosed in the prior art. On that
`issue, the court found:
`A [person of ordinary skill in the art] would have a
`considerable understanding of organic chemistry.
`Based on his or her understanding of the chemical
`properties of dexmedetomidine, a [person of ordi-
`nary skill in the art] would have expected it to be
`stable in room-temperature storage conditions for
`at least five months.
`Opinion, 343 F. Supp. 3d at 841. To reach that finding, the
`court relied on expert testimony that the chemical struc-
`ture of dexmedetomidine would be “a rock stable molecule”
`under normal conditions based on its aromatic ring struc-
`ture and lack of hydrolyzable and oxidizable groups. Id. at
`852. The court also relied on information in the Precedex
`Concentrate and Dexdomitor labels, which do not contain
`chemical stabilizers despite their low concentrations. And
`the court credited expert testimony that the about 2% lim-
`itation is consistent with standard industry expectations
`for drug stability. Moreover, the court rejected each of Hos-
`pira’s arguments, finding that Hospira had failed to show
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`that a person of skill would have expected a lower concen-
`tration to reduce stability or that a person of skill would
`have expected oxidation to occur in the absence of nitrogen
`sparging. Id. at 854–57.
`Based on its factual findings, the district court con-
`cluded that claim 6 of the ’106 patent is invalid as obvious
`and entered judgment in favor of Fresenius. Hospira ap-
`pealed the court’s judgment. We have jurisdiction under
`28 U.S.C. § 1295(a)(1).
`
`DISCUSSION
`On appeal from a bench trial, we review a district
`court’s conclusions of law de novo and its findings of fact
`for clear error. Braintree Labs., Inc. v. Novel Labs., Inc.,
`749 F.3d 1349, 1358 (Fed. Cir. 2014) (citing Brown & Wil-
`liamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120,
`1123 (Fed. Cir. 2000)). “A factual finding is clearly errone-
`ous when, despite some supporting evidence, we are left
`with a definite and firm conviction that the district court
`was in error.” Alcon Research Ltd. v. Barr Labs., Inc., 745
`F.3d 1180, 1186 (Fed. Cir. 2014) (citing Alza Corp. v. Mylan
`Labs., Inc., 464 F.3d 1286, 1289 (Fed. Cir. 2006)). “The
`burden of overcoming the district court’s factual findings
`is, as it should be, a heavy one.” Polaroid Corp. v. Eastman
`Kodak Co., 789 F.2d 1556, 1559 (Fed. Cir. 1986). “Where
`there are two permissible views of the evidence, the fact-
`finder’s choice between them cannot be clearly erroneous.”
`Anderson v. Bessemer City, 470 U.S. 564, 574 (1985) (citing
`United States v. Yellow Cab Co., 338 U.S. 338, 342 (1949)).
`Obviousness is a question of law based on underlying
`facts, including the scope and content of the prior art. See
`Kinetic Concepts, Inc. v. Smith & Nephew, Inc., 688 F.3d
`1342, 1360 (Fed. Cir. 2012). “The inherent teaching of a
`prior art reference is a question of fact.” Par Pharm. v. TWI
`Pharm., Inc., 773 F.3d 1186, 1194 (Fed. Cir. 2014) (citation
`omitted). When the prior art does not expressly disclose a
`claim limitation, “inherency may supply a missing claim
`
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`limitation in an obviousness analysis.” Id. at 1194–95 (col-
`lecting cases). Inherency is established in the context of
`obviousness when “the limitation at issue necessarily must
`be present, or the natural result of the combination of ele-
`ments explicitly disclosed by the prior art.” Id. at 1195–96.
`In this appeal, Hospira challenges the district court’s
`conclusion that claim 6 of the ’106 patent is invalid as ob-
`vious based on the inherency of the “about 2%” limitation.
`First, Hospira argues that the district court incorrectly
`considered the inherency of the about 2% limitation in non-
`prior art embodiments rather than the allegedly obvious
`prior art combination. Second, Hospira argues that the
`court applied a lower “reasonable expectation of success
`standard” rather than the higher “necessarily present”
`standard to the inherency question. We address each of
`these arguments in turn.
`
`I
`We first consider Hospira’s argument that the district
`court erred in its application of the inherency doctrine by
`considering the inherent properties of non-prior art embod-
`iments. Hospira argues that every tested sample of the
`4 µg/mL preferred embodiment in the record was either
`from Hospira’s NDA for Precedex Premix or from Frese-
`nius’s ANDA for its ready-to-use product, none of which
`were in the prior art. Hospira’s primary contention is that
`each of those samples was manufactured using the partic-
`ular manufacturing process described in Example 5 of the
`’106 patent, and thus the stability data from those samples
`cannot suffice to prove that all samples of the allegedly ob-
`vious combination—a formulation of the 4 µg/mL preferred
`embodiment which may or may not have been prepared us-
`ing the manufacturing process of Example 5—would “nec-
`essarily” meet the about 2% limitation.
`Fresenius responds that the district court did not err
`in relying on the tested samples of the 4 µg/mL preferred
`embodiment in the record, and it is irrelevant for the
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`inherency analysis whether or not those samples were
`prior art. Fresenius contends that Hospira’s argument
`that unclaimed manufacturing variables from Example 5
`distinguish the tested samples from the prior art is a new
`argument raised for the first time on appeal and is there-
`fore improper, and in any event is unfounded.
`As a threshold matter, we agree with Fresenius that
`the district court did not err in relying on data obtained
`after the priority date of the ’106 patent in its inherency
`analysis. Extrinsic evidence can be used to demonstrate
`what is “necessarily present” in a prior art embodiment
`even if the extrinsic evidence is not itself prior art. See
`Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co.,
`878 F.3d 1336, 1345 (Fed. Cir. 2018) (allowing “non-prior
`art data” to be used to support inherency); Schering Corp.
`v. Geneva Pharm., Inc., 339 F.3d 1373, 1377 (Fed. Cir.
`2003) (finding that the prior art need not recognize the in-
`herent property). Moreover, the work of the inventor or the
`patentee can be used as the evidence of inherency. See, e.g.,
`Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362, 1369
`(Fed. Cir. 2012) (analyzing inherency based on the disclo-
`sure of the “patent itself”); Telemac Cellular Corp. v. Topp
`Telecom, Inc., 247 F.3d 1316, 1327–28 (Fed. Cir. 2001)
`(finding that features were inherent “as evidenced by [the
`patentee]’s own documents”). The later evidence is not it-
`self prior art; it only helps to elucidate what the prior art
`consisted of. Therefore, it was not legally incorrect for the
`district court to rely on non-prior art data from Hospira’s
`NDA and Fresenius’s ANDA as evidence of the inherent
`stability of the 4 µg/mL preferred embodiment.
`Furthermore, we agree with Fresenius that the un-
`claimed manufacturing variables in Example 5 do not, as a
`matter of law, preclude a finding of inherency in this case.
`First, although Hospira faults the district court for looking
`only at samples prepared by the manufacturing process of
`Example 5, it is not entirely clear that Hospira actually ar-
`gued below that the inherency analysis required stability
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`data from samples prepared by manufacturing processes
`other than Example 5. But even assuming that Hospira
`preserved that argument by raising it to the district court,
`it is without merit. Claim 6 is directed to a composition of
`4 µg/mL dexmedetomidine disposed in a sealed glass con-
`tainer. ’106 patent col. 26 ll. 18–24, 41–43. Claim 6 is not
`a method claim, it is not a product-by-process claim, and
`there are no limitations in claim 6 regarding the manufac-
`turing process by which the recited 4 µg/mL dexmedetomi-
`dine composition must be prepared. Importing such
`limitations from Example 5 into the claim, as Hospira
`seeks to do, would be improper. See Phillips v. AWH Corp.,
`415 F.3d 1303, 1323 (Fed. Cir. 2005). Thus, the district
`court did not misapply the law of inherency by considering
`the samples in the record without regard to the process by
`which those samples were prepared.
`Because the district court did not legally err in apply-
`ing the inherency doctrine, what remains for our review is
`the court’s factual finding that the about 2% limitation was
`necessarily present in the 4 µg/mL preferred embodiment.
`At trial, Fresenius presented evidence in support of its in-
`herency contention. That evidence included data from
`more than 20 samples of the 4 µg/mL preferred embodi-
`ment, every one of which met the about 2% limitation. The
`evidence also included expert testimony that concentration
`does not affect the stability of dexmedetomidine, which
`demonstrates that dexmedetomidine is a very stable drug.
`The district court relied on that evidence to find that the
`about 2% limitation was necessarily present in the 4 µg/mL
`preferred embodiment in the prior art.
`Hospira disagrees with the factual findings of the dis-
`trict court. For example, Hospira asks us to find that the
`samples in the record are not representative of every pos-
`sible formulation of the 4 µg/mL preferred embodiment.
`But Hospira did not present evidence of even a single sam-
`ple of the 4 µg/mL preferred embodiment that failed to
`meet the about 2% limitation. Additionally, Hospira did
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`not present evidence sufficient to persuade the district
`court that the manufacturing process of Example 5 was the
`reason why all tested samples met the about 2% limitation,
`or that samples prepared by a different process might not
`meet that limitation. See Acorda Therapeutics, Inc. v. Rox-
`ane Labs., Inc., 903 F.3d 1310, 1335–36 (Fed. Cir. 2018)
`(noting that the patent owner “cites no support” for the as-
`sumption that inherent properties would differ between
`the prior art and the claim).
`Hospira also insists that the district court erred by not
`requiring Fresenius to present a quantitative drug loss
`model. But Hospira presented that factual contention at
`trial, and the court rejected it. The court instead credited
`the testimony of Fresenius’s expert that there was not
`enough drug loss to be able to discern one drug loss model
`from another. The court found that, “[i]f anything, the in-
`ability to assign a loss model to dexmedetomidine under-
`scores Fresenius Kabi’s position that the 4 µg/mL preferred
`embodiment will necessarily experience no more than two
`percent loss in concentration at five months.” Opinion,
`343 F. Supp. 3d at 849.
`Hospira’s arguments on appeal cannot change the trial
`record, which included more than 20 samples that all met
`the about 2% limitation. The trial record also included tes-
`timonial and statistical evidence that dexmedetomidine is
`a very stable drug at any concentration; thus, simply add-
`ing solvent to dilute it by a factor of 25—from 100 µg/mL,
`which was known to be stable, to 4 µg/mL—does not affect
`its inherent stability. On that record, it was not clearly
`erroneous for the district court to find that the about 2%
`limitation was necessarily present in the prior art.
`II
`We turn to Hospira’s argument that the district court
`applied the wrong standard to the inherency question.
`Hospira argues that the district court applied the “reason-
`able expectation of success” standard in its inherency
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`HOSPIRA, INC. v. FRESENIUS KABI USA, LLC
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`analysis of the chemical structure of dexmedetomidine.
`Thus, Hospira argues, the district court did not conduct a
`complete inherency analysis under the correct “necessarily
`present” standard.
`Fresenius responds that the district court completed its
`inherency analysis when it found that the about 2% limita-
`tion was necessarily present in the prior art based on the
`evidence of the tested samples in the record. Fresenius ar-
`gues that, after completing that correct analysis of inher-
`ency, the court then separately found that a person of
`ordinary skill would have had a reasonable expectation of
`success in achieving the about 2% limitation.
`“An obviousness determination requires that a skilled
`artisan would have perceived a reasonable expectation of
`success in making the invention in light of the prior art.”
`Amgen Inc. v. F. Hoffman-La Roche, Ltd., 580 F.3d 1340,
`1362 (Fed. Cir. 2009). In this appeal, the parties do not
`dispute that Fresenius met its burden of proof on that is-
`sue. See Appellant’s Br. 37 (“[T]he District Court found a
`reasonable expectation of success; although Hospira re-
`spectfully disagrees with the District Court’s conclusion on
`this issue, it acknowledges the deferential standard of re-
`view and does not contend that this finding is clearly erro-
`neous.”). Thus, the only dispute is whether the district
`court’s inherency analysis was correct. We agree with
`Fresenius that it was.
`As explained above, the district court engaged in a
`thorough and extensive analysis of the stability data in the
`record to reach its factual finding that the about 2% limi-
`tation was necessarily present in the prior art. Opinion,
`343 F. Supp. 3d at 841, 845–51. But the district court then
`engaged in unnecessary analysis in evaluating whether the
`chemical properties of the dexmedetomidine molecule, the
`information in the Precedex Concentrate and Dexdomitor
`labels, and the industry guidance for stability testing
`would enable a person of ordinary skill to have had a
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`15
`
`reasonable expectation of successfully achieving the about
`2% limitation. Id. at 851–57. The court thus conflated the
`standards for inherency and reasonable expectation of suc-
`cess. However, that was harmless error that did not infect
`its inherency analysis and findings. See Vanderbilt Univ.
`v. ICOS Corp., 601 F.3d 1297, 1308 (Fed. Cir. 2010) (“The
`district court’s findings demonstrate that under the correct
`legal test, [the plaintiff] did not carry its burden. Thus, any
`erroneous interpretations of our case law were harmless
`error.”); see also Environ Prods. v. Furon Co., 215 F.3d
`1261, 1266 (Fed. Cir. 2000) (“When the error as to the
`weight of proof could not have changed the result, the erro-
`neous instruction is harmless.” (citing 11 CHARLES ALAN
`WRIGHT & ARTHUR R. MILLER, FEDERAL PRACTICE AND
`PROCEDURE § 2886 (2d ed. 1995))). If a property of a com-
`position is in fact inherent, there is no question of a reason-
`able expectation of success in achieving it. The claimed
`dexmedetomidine formulation already is, as the evidence
`in this case shows, possessed of the about 2% limitation.
`III
`Having concluded that the district court’s factual find-
`ings were not clearly erroneous, we finally turn to the legal
`question of whether those findings support a conclusion
`that claim 6 would have been obvious. We conclude that
`they do.
`It is well-settled that the inclusion of an inherent, but
`undisclosed, property of a composition does not render a
`claim to the composition nonobvious. Atlas Powder Co. v.
`Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he dis-
`covery of a previously unappreciated property of a prior art
`composition, or of a scientific explanation for the prior art’s
`functioning, does not render the old composition patenta-
`bly new to the discoverer.” (citing Titanium Metals Corp. v.
`Banner, 778 F.2d 775, 782 (Fed. Cir. 1985))). A patent can
`be invalid based on inherency when the patent itself makes
`clear that a limitation is “not an additional requirement
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`imposed by the claims . . . , but rather a property neces-
`sarily present.” In re Kubin, 561 F.3d 1351, 1357 (Fed. Cir.
`2009); see also Persion Pharm. LLC v. Alvogen Malta Oper-
`ations Ltd., Case No. 18-2361, slip op. at 13 (Fed. Cir. Dec.
`27, 2019) (“[T]he district court did not err by finding that
`the pharmacokinetic limitations of the asserted claims
`were inherent and added no patentable weight to the phar-
`macokinetic claims.”); Alcon Research, 687 F.3d at 1369
`(“[T]his claim language does not impose any additional re-
`quirement because the ’805 patent itself defines mast cell
`stabilization as a property that is necessarily present at
`those concentrations.”); In re Kao, 639 F.3d 1057, 1070
`(Fed. Cir. 2011) (“Substantial evidence supports the
`Board’s finding, based upon the specification, which con-
`firms that the claimed ‘food effect’ is an inherent property
`of oxymorphone itself . . . .”).
`Here, the ’106 patent itself states that the invention
`was based on “the discovery that dexmedetomidine pre-
`pared in a premixed formulation . . . remains stable and
`active after prolonged storage.” ’106 patent, col. 3 ll. 6–10
`(emphasis added). Claim 6 does not recite any manufac-
`turing limitations that are related to stability or an added
`component that enhances stability; it simply recites a com-
`position, with a “wherein” clause that describes the stabil-
`ity of that recited composition, a result that was inherent
`in the prior art.
`In sum, the district court did not clearly err in finding
`as a factual matter that the about 2% limitation was nec-
`essarily present in the prior art, and as a legal matter the
`inclusion of the inherent about 2% limitation does not
`make claim 6 nonobvious. We therefore agree with the dis-
`trict court’s conclusion that claim 6 of the ’106 patent would
`have been obvious over the prior art.
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`17
`
`CONCLUSION
`We have considered Hospira’s remaining arguments,
`but we find them unpersuasive. Accordingly, the judgment
`of the district court is affirme