Hospira, Inc. v. Fresenius Kabi USA, LLC

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. 2 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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. HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 3 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. 4 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 5 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: 6 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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. HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 7 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. 8 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 9 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 10 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 11 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 12 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 13 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 14 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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 16 HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 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. HOSPIRA, INC. v. FRESENIUS KABI USA, LLC 17 CONCLUSION We have considered Hospira’s remaining arguments, but we find them unpersuasive. Accordingly, the judgment of the district court is affirmed. AFFIRMED