In a recent precedential opinion[1], the Federal Circuit rejected arguments by Amgen that a single step purification process used by Sandoz for its G-CSF biosimilar infringed claims of Amgen’s patent describing a multistep purification procedure for proteins expressed in a non-mammalian system.

In this case, the Federal Circuit explained that the doctrine of equivalents is not a second prong to patent infringement that enables patent holders to extend the scope of their claims, but rather applies only to exceptional cases.

The appeal stems from two decisions out of the Northern District of California related to patent infringement actions brought by Amgen, Inc. and Amgen Manufacturing, Ltd. (“Amgen”) against Sandoz Inc., Sandoz International Gmbh, and Sandoz Gmbh (“Sandoz”).  The appeal centers on the lower court’s grant of summary judgement of noninfringement of claim 7 of Amgen’s U.S. Patent No. 8,940,878 (“the ’878 patent”) and claim 1 of Amgen’s U.S. Patent No. 6,162,427 (“the ’427 patent”) by Sandoz’s filgrastim biosimilar and its proposed pegfilgrastim biosimilar.

Amgen’s primary patents covering its filgrastim and pegfilgrastim biologics (marketed as Neupogen® and Neulasta®, respectively) expired in 2013 and 2015.  Amgen’s ’878 patent is directed to purifying proteins expressed in non-mammalian systems in both non-native soluble and non-native insoluble forms, including direct capture of such proteins from a refold mixture or a cell lysate pool by a separation matrix.

Sandoz submitted an abbreviated Biologics License Application (“aBLA”) to the Food and Drug Administration (“FDA”) in 2014 in order to market its filgrastim biosimilar, which it later launched after receiving approval in 2015.  Sandoz also submitted an aBLA to market its pegfilgrastim biosimilar in 2016, which has not yet been approved.  Subsequently, Amgen filed an amended infringement complaint in connection with the Sandoz’s filgrastim biosimilar product and later filed an infringement complaint in connection with Sandoz’s pegfilgrastim application, asserting its ’878 and ’427 patents.

In its complaint, Amgen asserted, inter alia, that the process used by Sandoz to manufacture its biosimilar products infringes claim 7 of the ’878 patent.  The purification process used by Sandoz involves a single anion exchange chromatography step with one solution that comprises continuously flowing a refold solution containing filgrastim, a detergent, and other selected components, through a separation matrix.

Claim 7 of Amgen’s ’878 patent recites, in pertinent part:

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

(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 ’878 patent describes standard capture media used in (e)-(g), providing that the “separation matrix” can be affinity resin, such as an affinity resin selected from the group consisting of Protein A, Protein G and a synthetic mimetic affinity resin, or it can be a non-affinity resin, such as a non-affinity resin selected from the group consisting of ion exchange, mixed mode, and a hydrophobic interaction resin[2].

After applying the refold solution to the separation matrix, the method further comprises (f) “washing the separation matrix” with “any composition, as long as the composition and pH of the wash buffer is compatible with both the protein and the matrix” and (g) “eluting the protein from the separation matrix” using “a solution that interferes with the binding of the adsorbent component of the separation matrix to the protein.”[3]

The district court construed the elements (e)-(g) of claim 7 as three separate steps, including:

(e) applying the refold solution to a column that contains the separation matrix…,

(f) adding a solution into the column…to remove materials in the refold solution that do not interact with the separation matrix…; and

(g) adding a solution into the column…which [h]as the effect of reversing the interactions between the protein and the separation matrix….

(Emphasis added)[4].  As a result, the lower court granted summary judgment that Sandoz’s single step purification process for its filgrastim and pegfilgrastim biosimilars does not infringe claim 7 of the ’878 patent.

Appealing to the Federal Circuit, Amgen argued that the claims of the ’878 patent cover any number of solutions or steps[5]. Amgen asserted that the claim only specifies that the washing and eluting steps are performed in sequence[6].  Amgen argued that, as a result, Sandoz’s purification process infringes claim 7 of the ’878 patent because the refolding solution flowing through the separation matrix would be washed and eluted at any point along the matrix[7].

In response, the Federal Circuit found that the claims when read in light of the specification clearly define the washing and separating procedures as separate functional steps[8].  As a result, the Court found that Sandoz’s purification process employing a single step and solution does not literally infringe claim 7 of the ’878 patent[9].

Amgen also argued that Sandoz’s purification process infringes under the doctrine of equivalents because it “achieves the same functions (washing and eluting), in substantially the same way (binding protein preferentially compared to contaminants, and then raising salt concentration to reverse protein binding) to achieve the same result (protein purification).”[10]

The Federal Circuit responded that Amgen argued beyond the scope of the claims in the ’878 patent.  The Court held that Sandoz’s single step purification process does not function in substantially the same way as the claimed three step process[11]. In this regard, the Court asserted that “[t]he doctrine of equivalents applies only in exceptional cases and is not ‘simply the second prong of every infringement charge, regularly available to extend protection beyond the scope of the claims.’”[12]  Thus, the Court declined to extend the scope of the claims reciting “refolding, “washing,” and “eluting” to cover “nearly any type of adsorbent chromatographic separation” under a doctrine of equivalence, thereby effectively reading out the additional steps required by the claim[13] 

Amgen also appealed a decision by the lower court that Sandoz did not infringe claim 1 of the ’427 patent.  The ’427 patent involves administering G-CSF before providing chemotherapy to a patient.  In pertinent part, claim 1 of the requires “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.”

The lower court construed a “disease treating-effective amount of at least one chemotherapeutic agent” as “an amount sufficient to treat a disease for which at least one chemotherapeutic agent is prescribed.”[14]

Amgen argued that the “disease treating-effective amount” includes administering a chemotherapeutic for the purpose of mobilizing stem cells[15].

The Federal Circuit disagreed, finding that “disease treating-effective amount” requires an amount of chemotherapeutic sufficient to treat the underlying disease[16].

The Court explained that Amgen cannot read the claims differently than they are drafted, specifically, “[h]ad Amgen simply wanted to claim a method of mobilizing stem cells, in any context, it could have done so.”[17]

While the Court’s ultimate conclusion regarding the claim language at issue may not be surprising, after the Court’s ruling in this case, patentees may find enforcing a broader scope of their patent claims more difficult going forward.  As a result, practitioners may need to keep the court’s narrowed view of the doctrine of equivalents in mind for all areas of claim construction practice.

Both inventors and practitioners may also need to be mindful of this case when drafting claims and prosecuting application before the USPTO.  The Court’s decision highlights a heightened need for express language capturing the desired subject matter to be claimed, as it may be more difficult to assert claims under the doctrine of equivalents.

[1] Amgen, Inc. v. Sandoz Int’l GmbH, Appeal No. 2018-1551, slip op. (Fed. Cir. May 8, 2019)

[2] ’878 patent at col. 2, lines 7-12.

[3] ’878 patent at col. 15 line 47 – col. 16, line 9.

[4] Amgen, slip op. at 8

[5] Amgen, slip op. at 8.

[6] Id.

[7] Id.

[8] Id.  (citing Mformation Techs., Inc. v. Research in Motion Ltd., 764 F.3d 1392(Fed. Cir. 2014)); see e.g., (“a claim “requires an ordering of steps when the claim language, as a matter of logic or grammar, requires that the steps be performed in the order written, or the specification directly or implicitly requires”) (citingTop of Form TALtech Ltd. v. Esquel Apparel, Inc., 279 F. App’x 974, 978 (Fed. Cir. 2008)).

[9] Amgen, slip op. at 9.

[10] Id. at 10 (citing Appellant Br. 52).

[11] Id. at 11.

[12] Id. (quoting London v. Carson Pi-rie Scott & Co., 946 F.2d 1534, 1538 (Fed. Cir. 1991)).

[13] 11.

[14] Id. at 6.

[15] Id. at 14.

[16] Id. at 15.

[17] Id.