Amgen Inc. v. Sandoz Inc.

923 F.3d 1023

AMGEN INC., Amgen Manufacturing, Limited, Plaintiffs-Appellants

v.SANDOZ INC., Sandoz International GMBH, Sandoz GMBH, Defendants-Appellees

Amgen Inc., Amgen Manufacturing, Limited, Plaintiffs-Appellants

v.Sandoz Inc., Sandoz International GMBH, Sandoz GMBH, LEK Pharmaceuticals, D.D., Defendants-Appellees

2018-1551

2018-1552

United States Court of Appeals, Federal Circuit.

Decided: May 8, 2019

Nicholas P. Groombridge, Paul, Weiss, Rifkind, Wharton & Garrison LLP, New York, NY, argued for plaintiffs-appellants. Also represented by Jennifer Gordon, Golda Lai, Stephen Accursio Maniscalco, Peter Sandel, Eric Alan Stone, Jacob Whitt, Jennifer H. Wu ; Lois M. Kwasigroch, Kimberlin L. Morley, Wendy A. Whiteford, Amgen Inc., Thousand Oaks, CA.

Deanne Maynard, Morrison & Foerster LLP, Washington, DC, argued for defendants-appellees. Also represented by Bryan Leitch, Brian Robert Matsui ; Erik Jeffrey Olson, Eric C. Pai, Palo Alto, CA.

Before Lourie, O’Malley, and Reyna, Circuit Judges.

Lourie, Circuit Judge.

Amgen Inc. and Amgen Manufacturing Ltd. (collectively, "Amgen") appeal from two decisions of the United States District Court for the Northern District of California in two patent infringement actions brought by Amgen under the Biologics Price Competition and Innovation Act ("BPCIA"), 42 U.S.C. § 262 (2012). The court construed claims of U.S. Patents 6,162,427 (the " ’427 patent") and 8,940,878 (the " ’878 patent"), Amgen Inc. v. Sandoz Inc. , No. 14-CV-04741-RS, 2016 WL 4137563 (N.D. Cal. Aug. 4, 2016) (" Claim Construction Order "), and granted summary judgment of noninfringement of claim 7 of the ’878 patent by Sandoz’s filgrastim biosimilar and its proposed pegfilgrastim biosimilar, Amgen Inc. v. Sandoz Inc. , 295 F. Supp. 3d 1062, 1064 (N.D. Cal. 2017) (" Decision "). We conclude that the district court correctly construed the claims and granted summary judgment of noninfringement of claim 7. The judgment of the district court is therefore affirmed.

BACKGROUND

Amgen created and commercialized two related biologic products, filgrastim (marketed as Neupogen^®) and pegfilgrastim (marketed as Neulasta^®), indicated for treating neutropenia, a deficiency of white blood cells. Neutropenia often results from exposure to certain chemotherapeutic regimens or radiation therapy during cancer treatment. Filgrastim is a recombinant analog of granulocyte-colony stimulating factor ("G-CSF"), a naturally-occurring human glycoprotein that stimulates the production of neutrophils and stem cells and their release into the bloodstream. Pegfilgrastim is materially identical but much larger because it is conjugated to a polyethylene glycol molecule, which enables long-acting administration. Both of Amgen’s products are generally indicated to stimulate neutrophil production, and Neupogen^® is further indicated to mobilize stem cells from the bone marrow into the bloodstream for collection for autologous stem cell transplantation.

In 2014, Sandoz submitted to the Food and Drug Administration ("FDA") an abbreviated Biologics License Application ("aBLA") to market a biosimilar filgrastim product. While Sandoz’s aBLA referenced Neupogen^®, Sandoz elected not to provide Amgen with its aBLA or manufacturing information. In October 2014, Amgen filed a complaint for, inter alia , a declaratory judgment that Sandoz’s proposed biosimilar would infringe the ’427 patent. See 35 U.S.C. § 271(e)(2)(C) (defining submission of an aBLA as an act of patent infringement); 42 U.S.C. § 262(l)(9)(C) (allowing a reference product sponsor to bring a declaratory judgment action regarding "any patent that claims the biological product or a use of the biological product" when the biosimilar applicant does not provide its aBLA and manufacturing information).¹ In 2015, Sandoz received FDA approval for its filgrastim biosimilar, Zarxio^®. After Sandoz launched Zarxio^®, Amgen amended its complaint to plead infringement of the ’878 patent under 35 U.S.C. §§ 271(e)(2)(C)(ii), (g).

In 2015, Sandoz submitted an aBLA to market a biosimilar pegfilgrastim product referencing Neulasta^®. In May 2016, Amgen filed a complaint for infringement of the ’878 patent under 35 U.S.C. § 271(e)(2)(C)(i) and 42 U.S.C. § 262(l)(6)(A). Sandoz has not yet received approval for its proposed pegfilgrastim biosimilar.

The ’878 patent discloses methods of protein purification by adsorbent chromatography, a well-known method that involves separating the components of a solution ("the mobile phase") based upon their chemical attraction to the molecules or ions that comprise a stationary separation matrix ("the stationary phase"). The ’878 patent refers to several methods of chromatography, including protein affinity and non-protein affinity methods like ion exchange. ’878 patent col. 15 ll. 17–24. The ’878 patent further discloses use of a salt or pH gradient to control the elution of the protein of interest, as well as the preceding elution (or "washing") from the matrix of unwanted components of a refold solution containing the protein of interest. Id. col. 16 ll. 2–22. Claim 7, recited below, is directed to the use of a non-affinity separation matrix.

7. A method of purifying a protein expressed in a non-native limited solubility form in a non-mammalian expression system comprising:

(a) expressing a protein in a non-native limited solubility form in a non-mammalian cell;

(b) lysing a non-mammalian cell;

(c) solubilizing the expressed protein in a solubilization solution comprising one or more of the following:

(i) a denaturant;

(ii) a reductant; and

(iii) a surfactant;

(d) forming a refold solution comprising the solubilization solution and a refold buffer, the refold buffer comprising one or more of the following:

(i) a denaturant;

(ii) an aggregation suppressor;

(iii) a protein stabilizer; and

(iv) a redox component;

(e) directly applying the refold solution to a separation matrix under conditions suitable for the protein to associate with the matrix;

(f) washing the separation matrix; and

(g) eluting the protein from the separation matrix, wherein the separation matrix is a non-affinity resin selected from the group consisting of ion exchange, mixed mode, and a hydrophobic interaction resin.

The ’427 patent discloses methods of treating "diseases requiring peripheral stem cell transplantation." ’427 patent col. 1 ll. 9–10. Certain cancer treatments, like chemotherapy and radiation, can destroy stem cells, so stem cells are often collected from a person’s bloodstream in a process called leukapheresis and re-infused after such treatment. The claimed invention lies in administering G-CSF before chemotherapy to "achiev[e] a superior yield of stem cells," so that fewer leukaphereses are required to achieve the stem cell transplant. Id. col. 1 ll. 58–61. Representative claim 1 reads:

1. A method of treating a disease requiring peripheral stem cell transplantation in a patient in need of such treatment, comprising

administering to the patient a hematopoietic stem cell mobilizing-effective amount of G-CSF; and

thereafter administering to the patient a disease treating-effective amount of at least one chemotherapeutic agent.

No other claim from either the ’427 patent or the ’878 patent is before us in this appeal.

The district court construed "disease treating-effective amount of at least one chemotherapeutic agent" in claim 1 of the ’427 patent as limited to "[a]n amount sufficient to treat a disease for which at least one chemotherapeutic agent is prescribed." Claim Construction Order , 2016 WL 4137563, at *18. The court thereby rejected Amgen’s argument that the amount must be "sufficient to enhance the mobilization of stem cells," id. at *6–7, regardless of its effect on the underlying disease. Amgen thereafter stipulated to noninfringement of the ’427 patent contingent upon its right to appeal from the district court’s claim construction order. J.A. 49–53.

With respect to the ’878 patent, the district court treated the Neupogen^® and Neulasta^® cases together. It construed limitations (f) and (g) of claim 7 (the "washing" and "eluting" steps) as separate steps and further clarified that the eluting step "must occur after the step of ‘washing the separation matrix.’ " Claim Construction Order , 2016 WL 4137563, at *18. As construed, performing limitations (e)–(g) of the process of claim 7 requires:

(e) applying the refold solution to a separation matrix ... ,

(f) applying a solution to remove ... unwanted components of the refold solution ... while preserving [protein] binding ...; and

(g) applying a solution that reverses the binding of the purified protein ....

Id.

Since it is undisputed that Sandoz’s process only involves one step—applying the refold solution to the matrix, with no separate washing or eluting steps—the district court granted summary judgment that neither Zarxio^® nor Sandoz’s proposed pegfilgrastim biosimilar infringes claim 7 of the ’878 patent. Decision , 295 F. Supp. 3d at 1071.

Amgen appeals. We have jurisdiction under 28 U.S.C. § 1295(a)(1).

DISCUSSION

We review a district court’s grant of summary judgment according to the law of the regional circuit. Kaneka Corp. v. Xiamen Kingdomway Grp. Co. , 790 F.3d 1298, 1303 (Fed. Cir. 2015) (citing Halo Elecs., Inc. v. Pulse Elecs., Inc. , 769 F.3d 1371, 1377 (Fed. Cir. 2014) ). In the Ninth Circuit, summary judgment is reviewed de novo , Brunozzi v. Cable Commc’ns, Inc. , 851 F.3d 990, 995 (9th Cir. 2017) (citing Ctr. for Bio-Ethical Reform, Inc. v. L.A. Cty. Sheriff Dep’t , 533 F.3d 780, 786 (9th Cir. 2008) ), and is appropriate when, viewing the evidence in favor of the non-movant, there is no genuine dispute of material fact, Zetwick v. Cty. of Yolo , 850 F.3d 436, 440 (9th Cir. 2017) (citing United States v. JP Morgan Chase Bank Account No. Ending 8215 , 835 F.3d 1159, 1162 (9th Cir. 2016) ).

Claim construction is ultimately an issue of law, which we review de novo . Shire Dev., LLC v. Watson Pharm., Inc. , 787 F.3d 1359, 1364 (Fed. Cir. 2015). We ...