Endo Pharm. Inc. v. Actavis LLC

922 F.3d 1365

ENDO PHARMACEUTICALS INC., Mallinckrodt LLC, Plaintiffs-Appellees

v.ACTAVIS LLC, fka Actavis Inc., Actavis South Atlantic LLC, Teva Pharmaceuticals USA, Inc., Defendants-Appellants

2018-1054

United States Court of Appeals, Federal Circuit.

Decided: May 3, 2019

Martin Jay Black, Dechert LLP, Philadelphia, PA, argued for plaintiffs-appellees. Also represented by Sharon K. Gagliardi ; Blake Greene, Austin, TX; Jonathan Loeb, Mountain View, CA; Robert Rhoad, Princeton, NJ.

Jeffrey J. Toney, Kasowitz, Benson, Torres & Friedman LLP, Atlanta, GA, for plaintiff-appellee Mallinckrodt LLC. Also represented by Rodney R. Miller, Paul Gunter Williams.

John C. O'Quinn, Kirkland & Ellis LLP, Washington, DC, argued for defendants-appellants. Also represented by William H. Burgess ; Charles A. Weiss, Eric H. Yecies, Holland & Knight, LLP, New York, NY.

Before Wallach, Clevenger, and Stoll, Circuit Judges.

Dissenting opinion filed by Circuit Judge Stoll.

Wallach, Circuit Judge.

Appellees Endo Pharmaceuticals Inc. ("Endo Pharmaceuticals") and Mallinckrodt LLC ("Mallinckrodt") (collectively, "Endo") sued Appellants Actavis LLC, Actavis South Atlantic LLC, and Teva Pharmaceuticals USA, Inc. (collectively, "Actavis") in the U.S. District Court for the District of Delaware ("District Court"), alleging that two Abbreviated New Drug Applications filed by Actavis infringed claims 1–6 ("the Asserted Claims") of Mallinckrodt's U.S. Patent No. 8,871,779 ("the '779 patent"), which Endo Pharmaceuticals licenses. The District Court held that Actavis failed to "prove[ ] by clear and convincing evidence that any of the [A]sserted [C]laims ... were invalid" as obvious or anticipated, Endo Pharm. Inc. v. Actavis Inc. , No. 14-1381-RGA, 2017 WL 3731001, at *1 (D. Del. Aug. 30, 2017), and entered final judgment of infringement, based on a stipulation by Actavis, J.A. 1.

Actavis appeals, challenging the invalidity determination. We have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1) (2012). We affirm.

BACKGROUND

I. The '779 Patent

Entitled "Process for Preparing Morphinan-6-One Products with Low Levels of a,ß-Unsaturated Ketone Compounds," the '779 patent generally relates to compounds known as "morphinan alkaloids," such as "oxymorphone," which have "great medical importance" and "are used extensively for pain relief." '779 patent col. 1 ll. 24–30. "Morphinan compounds and analogs thereof typically have a ring structure ... corresponding to Formula (1)":

Id . col. 1 ll. 38–53. "[P]harmaceutically desirable morphinan compounds" often "have a ketone group^{[1 ]} on the C-ring of Formula (1) and a saturated bond[, i.e., single bond,] between the two carbon atoms positioned a and ß to the ketone on the C-ring." Id . col. 2 ll. 21–24. "[T]hese compounds may be referred to as morphinan-6-one compounds." Id . col. 2 ll. 28–29. "[T]he ketone is present on the C(6) carbon atom, with the a and ß carbon atoms being the C(7) and C(8) positions...." Id . col. 2 ll. 25–26.

In describing the prior art, the '779 patent explains that "[v]arious processes for producing morphinan-6-one compounds are known," and "many ... involve some form of catalytic hydrogenation^{[2 ]} of a,ß-unsaturated ketone intermediate compounds [ (‘ABUKs’) ]," i.e., applying catalytic hydrogenation to compounds containing ketone groups with double bonds between the a and ß carbon atoms to convert the double bonds to single bonds. Id . col. 2 ll. 29–32. However, "[ABUKs] may persist as impurities in the final products." Id . col. 2 ll. 43–45. These hydrogenation processes also "may tend to undesirably reduce the ketone[, a key functional part of morphinan-6-one compounds,] as well as reducing or removing the a,ß-unsaturation." Id . col. 2 ll. 47–48.

The '779 patent discloses "processes for preparing highly pure morphinan-6-one products" having a relatively low concentration of ABUKs present as impurities, which "involve treating a reaction mixture including a morphinan-6-one compound and an [ABUK] with a sulfur-containing compound." Id . col. 5 ll. 6–10. These processes can "effectively reduce[ ] the concentration of undesirable [ABUKs] to acceptable levels," id. col. 5 ll. 11–13, with the process employing a sulfur-containing compound that can reduce ABUK concentration "from levels of about 0.5% (by weight) or more to levels of not more than about 0.1% ..., or lower (e.g., about 0.01% ..., about 0.001% ..., or lower), with minimal side reactions, ketone reduction, and/or any other undesirable effects," id . col. 5 ll. 17–22.

The Asserted Claims recite:

1. A hydrochloride salt of oxymorphone comprising less than 0.001% of 14-hydroxymorphinone .^[3]

2. The hydrochloride salt of claim 1 comprising less than 0.0005% of 14-hydroxymorphinone .

3. A pharmaceutical acceptable form comprising the oxymorphone hydrochloride according to claim 1.

4. A hydrochloride salt of a morphinan-6-one compound corresponding to Formula (2):

comprising less than 0.001% measured by [high performance liquid chromatography ] of an [ABUK] corresponding to Formula (3):

wherein the morphinan-6-one compound is oxymorphone and wherein X is —N(R₁₇)—;

R₁ and R₂ are hydrogen;

R₃ is hydroxy;

R₁₀ is hydrogen;

R₁₄ is hydroxy; and

R₁₇ is methyl.

5. The hydrochloride salt of claim 4 comprising less than 0.0005% of 14-hydroxymorphinone .

6. A pharmaceutical formulation comprising the oxymorphone hydrochloride according to claim 4.

Id . col. 37 l. 58–col. 38 l. 61 (emphases added).

II. Prior Art References

The District Court determined three references constitute the prior art in this case. See Endo , 2017 WL 3731001, at *6–8. We present each in turn.

A. Weiss

A scientific article from 1957, see Ulrich Weiss, Derivatives of Morphine. II. Demethylation of 14-Hydroxycodeinone. 14-hydroxymorphinone and 8,14-Dihydroxydihydromorphinone , 22 J. Organic Chemistry 1505, 1505–08 (1957) ("Weiss") (J.A. 2295–98), discloses, inter alia, the use of catalytic hydrogenation to convert oxymorphone ABUK to oxymorphone. See J.A. 2297 (employing palladium charcoal "as catalyst" and teaching arriving at the result of 14-hydroxydihydromorphinone, i.e., oxymorphone). Weiss also recounts 8,14-dihydroxy-7,8-dihydromorphinone ("oxymorphone diol") as "the product of hydration of the double bond of [oxymorphone ABUK]," J.A. 2295, the "ready conversion of [oxymorphone ABUK] into [oxymorphone diol]," J.A. 2296, and the reversion of oxymorphone diol to oxymorphone ABUK through the application of hydrochloride, see J.A. 2295, 2297.

B. Chapman

Entitled "Process for Preparing Oxycodone Hydrochloride Having Less Than 25 [Parts Per Million (‘ppm’) ] 14-hydroxycodeinone," U.S. Patent Application No. 2005/0222188 ("Chapman") (J.A. 2464–90) discloses, inter alia, processes that employ catalytic hydrogenation to purify oxycodone ABUK into the salt form of oxycodone. See J.A. 2473 ("In certain embodiments of the present invention, the 14-hydroxycodeinone [i.e., oxycodone ABUK] is converted to oxycodone by hydrogenation ... in conjunction with a ... catalyst...."). Chapman recites processes that convert oxycodone ABUK to 8,14-dihydroxy-7,8-dihydrocodeinone ("oxycodone diol"), a precursor to oxycodone ABUK, which can revert to oxycodone ABUK through the compound's conversion to salt form and thereby frustrate purification. See J.A. 2473–74. But Chapman provides a reaction that can remove oxycodone diol from a sample prior to the completion of purification, and prevent oxycodone diol's reversion to oxycodone ABUK. See J.A. 2483–84 (Example 3).

C. Rapoport

A scientific article from 1967, see Henry Rapoport et al., The Synthesis of Thebaine and Northebaine from Codeinone Dimethyl Ketal , 89 J. Am. Chemical Soc'y 1942, 1942–47 (1967) ("Rapoport") (J.A. 2908–13), discloses, inter alia, a process involving the use of bisulfite addition to convert oxycodone ABUK to oxycodone, see J.A. 2908–09. This process takes advantage of differences in solubility of the products of reactions between bisulfites and oxycodone ABUK to separate oxycodone from oxycodone ABUK. See J.A. 2908–09.

DISCUSSION

Actavis contends that the District Court erred by, inter alia, (1) misconstruing the claim term 14-hydroxymorphinone, see Appellants' Br. 67–74; and (2) determining that the Asserted Claims were not obvious in light of the prior art, see id . at 36–66. We address each argument in turn.

I. Claim Construction

A. Standard of Review and Legal Standard

"The proper construction of a patent's claims is an issue of Federal Circuit law...." Powell v. Home Depot U.S.A., Inc. , 663 F.3d 1221, 1228 (Fed. Cir. 2011) (citation omitted). "[C]laim construction must begin with the words of the claims themselves." Amgen Inc. v. Hoechst Marion Roussel, Inc. , 457 F.3d 1293, 1301 (Fed. Cir. 2006) (citation omitted). "[W]ords of a claim are generally given their ordinary and customary meaning" that they "would have to a person of ordinary skill in the art [ (‘PHOSITA’) ] in question at the time of the invention." Phillips v. AWH Corp. , 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc) (internal quotation marks and citations omitted). The PHOSITA "is deemed to read the claim term not only in the context of the particular claim in which the disputed term appears, but in the context of the entire patent, including the specification." Id. at 1313.⁴ Prosecution history may also be used to supply additional evidence of claim terms' intended meaning. See Home Diagnostics, Inc. v. LifeScan, Inc. , 381 F.3d 1352, 1356 (Fed. Cir. 2004).⁵ "We review the district court's evaluation of the patent's intrinsic record during claim construction de novo." Info-Hold, Inc. v. Applied Media Techs. Corp. , 783 F.3d 1262, 1265 (Fed. Cir. 2015).

While courts may consider extrinsic evidence in claim construction, "such evidence is generally of less significance than the intrinsic record." Wi-LAN, Inc. v. Apple Inc. , 811 F.3d 455, 462 (Fed. Cir. 2016) (citation omitted). When, as here, "the district court ... look[s] beyond the patent's intrinsic evidence and ......