Amgen Inc. v. Sandoz Inc.

295 F. Supp. 3d 1062
District Court, N.D. California·Decided December 19, 2017·No. Case No. 14-cv-04741-RS; Case No. 16-cv-02581-RS·Published·Cited by 2 cases

Opinion

RICHARD SEEBORG, United States District Judge

I. INTRODUCTION

Defendants Sandoz Inc., Sandoz International GmbH, Sandoz GmbH, and Lek Pharmaceuticals d.d. (collectively, "Sandoz") move for summary judgment as to both noninfringement and damages. Plaintiffs Amgen Inc. and Amgen Manufacturing, Limited (collectively, "Amgen") oppose summary judgment and move, in the alternative, pursuant to Rule 56(d), to defer a ruling on noninfringement until additional information is produced regarding a pending modification to Sandoz's allegedly infringing process. For the reasons explained below, Sandoz's motion for summary judgment of noninfringement is granted. The motion for summary judgment regarding damages is denied as moot. Amgen's Rule 56(d) motion is denied.1

*1065II. BACKGROUND

Amgen and Sandoz compete to develop, manufacture, promote, and sell biopharmaceutical products. The products at issue here are filgrastim and pegfilgrastim. Filgrastim is the pharmaceutical analog of a protein that naturally occurs in the human body. It stimulates the production of a type of white blood cells ("neutrophils") vital to the human immune system and, accordingly, is useful for treating patients undergoing certain forms of cancer therapy (e.g., chemotherapy) that can cause neutrophil deficiency ("neutropenia"). Pegfilgrastim is a modified version of filgrastim that remains in the circulatory system for a substantially longer period of time and thus is "long acting." Amgen began selling filgrastim in 1991 under the brand name Neupogen ® and launched a pegfilgrastim product, Neulasta ®, in 2002. Sandoz brought to market an FDA-approved biosimilar filgrastim product, Zarxio®, in 2015. Sandoz also has submitted an application to offer a biosimilar pegfilgrastim product that is pending before the FDA.

As explained in the claim construction order, recombinant proteins like filgrastim are manufactured in a multi-step process. The process begins when scientists introduce human DNA into a host cell of a different species, such as E. Coli bacteria, causing the bacteria to produce human proteins. Before these proteins can be therapeutically useful, however, they must attain a three-dimensional shape. Trouble arises when the host cells produce proteins that lack this proper shape. These "unfolded" proteins accumulate in the host cell and form insoluble aggregates called "inclusion bodies." To remedy the problem, scientists break open (lyse) the host cell to release the inclusion bodies. They solubilize the inclusion bodies, mixing the proteins with various chemicals to create a solution. They then combine that solution with a "refold buffer" to cause the protein to take a workable, three-dimensional shape.

Once the protein has refolded, it must be separated from the chemicals used for solubilization and refolding. This step is called purification and typically involves applying the solution containing the refolded protein to a "separation matrix." Generally, the separation matrix can function in one of two ways. In "flow-through" purification the separation matrix attracts one or more of the unwanted chemicals used to solubilize and refold the protein. The protein itself, however, does not attach to the matrix and thus "flows through" and is collected. By contrast, in "capture purification" the separation matrix attracts and binds the protein so that the unwanted contaminants and chemicals flow through the matrix and are discarded. The purified protein is then eluted (i.e., released) from the separation matrix and collected.

The present dispute between Amgen and Sandoz began in 2014. Over the past three years, the litigation between the parties has involved multiple issues and multiple patents. The only patent that remains at issue, however, is U.S. Patent No. 8,940,878 ("the '878 patent"), entitled "Capture Purification Processes for Proteins Expressed in a Non-Mammalian System." As the name suggests, the '878 patent generally relates to processes for purifying proteins. Claim 7 of the patent *1066claims one such method. Amgen asserts that one of the steps in Sandoz's process for making and purifying filgrastim and pegfilgrastim ("the AEX step") infringes claim 7. Sandoz contends the AEX step does not infringe because it does not satisfy elements (e), (f) and (g) of claim 7:

(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.

While Amgen Inc. retains ownership of the '878 patent, Amgen Manufacturing Limited ("AML") is responsible for manufacturing Neupogen and Neulasta. AML does not practice the '878 patent method in manufacturing either product.2

III. LEGAL STANDARD

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Amgen Inc. v. Sandoz Inc., 295 F. Supp. 3d 1062 (N.D. Cal. 2017).

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